REVIEW | doi:10.20944/preprints202208.0502.v1
Subject: Life Sciences, Immunology Keywords: Trained immunity; innate immune memory; respiratory pathogens; BCG; next-generation vac-cines; COVID-19
Online: 30 August 2022 (03:55:12 CEST)
The COVID-19 pandemic exposed the vulnerability of current vaccine technologies characterized by a slow onset of action and antigen-specific immune response. Although parental vaccines offer long-term protection against homologous strains, they rely exclusively on adaptive immune memory to produce neutralizing antibodies that are ineffective against new vaccine variants. Moreover, growing evidence highlights the multifaceted functions of trained immunity to elicit a rapid and enhanced innate response against unrelated stimuli or pathogens to subsequent triggers. This review discusses the protective role of trained immunity against respiratory pathogens and the experimental models essential for evaluating novel inducers of trained immunity. We further elaborate on the potential of trained immunity to leverage protection against emerging pathogens via recognition of diverse antigens by pathogen recognition receptors (PPRs) on innate immune cells. We also propose integrating trained- with adaptive- immunity to shape next-generation vaccines by coupling each one's unique characteristics.
BRIEF REPORT | doi:10.20944/preprints202101.0416.v1
Subject: Life Sciences, Biochemistry Keywords: Respiratory Syncytial Virus, Molecular Diagnostic, Respiratory Viruses, Coronavirus, Bronchiolitis
Online: 21 January 2021 (12:12:25 CET)
Over two years (2012-2014), 719 nasopharyngeal samples were collected from 6 weeks to 12 months old infants presenting at emergency department with moderate to severe acute bronchiolitis. Viral testing was performed and we found 98% positive samples including 90% Respiratory Syncytial Virus, 34% Human Rhino Virus, and 55% viral co-detections with predominance of RSV/HRV co-infections (30%). Interestingly, we found that the risk of being infected by HRV is higher in the absence of RSV, suggesting interferences or exclusion mechanisms between these two viruses. Conversely, Coronavirus infection had no impact on the likelihood of co-infection involving HRV and RSV. Bronchiolitis is the leading cause of hospitalizations in infants before 12 months of age, and many questions about its role in the later chronic respiratory diseases (asthma and chronic obstructive pulmonary disease) do exist. Role of virus detection and burden of viral codetections need to be further explored, in order to understand the physiopathology of chronic respiratory diseases, a major public health issue.
REVIEW | doi:10.20944/preprints202004.0291.v1
Subject: Life Sciences, Biotechnology Keywords: respiratory acidosis; CO2 narcosis; acute respiratory distress syndrome; hyperoxia
Online: 17 April 2020 (01:59:51 CEST)
Since 1991, there has been an alarming increase in the number of unexplained physiological events (UPEs) reported and experienced by pilots of jet fighters across different fleets. The UPEs have resulted in grounding some airframes, loss of aircraft, and even loss of life. There is no single agreed-upon root cause of UPEs that has been identified, and therefore there is no reliable corrective action. This author analyzed the literature related to other industries where artificial hyperoxic gas mixes are employed and where similar adverse reports have been reported. I hypothesize that UPEs are caused by high-dose oxygen delivery in excess of officially approved oxygen schedules while airflow rates are often inadequate, at a time when the positive pressure breathing feature of their oxygen regulator is not used. In a setting where pulmonary vital capacity is adversely affected by G-maneuvers and oxygen- and G-induced atelectasis, tidal volume is reduced by flight gear, and effective gas exchange is not supported by adequate ventilation, these factors combine to produce respiratory acidosis, followed by acute respiratory distress syndrome, CO2 narcosis, and coma. Reports from field data related to incidents in F-18S/H, showing that emergency oxygen did not correct the hypoxia-like symptoms including long-lasting periods of incapacitation and prolonged headaches, lend support to our hypothesis.
ARTICLE | doi:10.20944/preprints201711.0198.v2
Subject: Life Sciences, Virology Keywords: human coronavirus; MERS-CoV; clinical features; upper respiratory tract infections; lower respiratory tract infections; respiratory viruses
Online: 30 January 2018 (09:52:03 CET)
Human coronaviruses cause both upper and lower respiratory tract infections in humans. In 2012 a sixth human coronavirus (hCoV) was isolated from a patient presenting with severe respiratory illness. The 60-year-old man died as a result of renal and respiratory failure after admission to a hospital in Jeddah, Saudi Arabia. The aetiological agent was eventually identified as a coronavirus and designated Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV has now been reported in more than 27 countries across the Middle East, Europe, North Africa and Asia. As of July 2017, 2040 MERS-CoV laboratory confirmed cases, resulting in 712 deaths, were reported globally, with a majority of these cases from the Arabian Peninsula. This review summarises the current understanding of MERS-CoV, with special reference to the (i) genome structure, (ii) clinical features, (iii) diagnosis of infection and (iv) treatment and vaccine development.
ARTICLE | doi:10.20944/preprints202008.0008.v1
Online: 2 August 2020 (10:38:52 CEST)
Background: Elevated respiratory rates (RR) have been described in several disease states, such as pneumonia, asthma and bronchiolitis. Despite this, there are few studies defining the range of RR found in healthy children. Available age percentiles for RR have been generated using methods that have the potential themselves to alter the rate. Aim: The aim of this study was to develop accurate percentile charts of RR specific for age in healthy children for potential use in pre-hospital care (first-aid), clinical medicine and for reference in respiratory research. Method: A newly developed optical respiratory sensor was used to measure RR which placed no restrictions on respiratory excursion. This technique enabled recording in awake children without the artefact of the observer’s presence on the subject’s RR. A cross-sectional sample of healthy children was obtained from maternity wards, childcare centres and schools in Brisbane, Queensland, Australia. Results: RR were observed in 560 awake and 103 sleeping children of which data from 343 awake and 94 sleeping children was used to create reference ranges for healthy children from newborn to 13 years of age. The recorded rates were significantly higher when children were awake compared to asleep. During quiet sleep, RR decreased from 40 (interquartile range 7) bpm at one month to 20 (interquartile range 3) in children aged 3 years. In awake children, RR ranged from a median of 40 bpm (interquartile range 18) at 1 year to 12 bpm (interquartile range 11) at 13 years respectively. Conclusion: The optical sensor was found to be an appropriate respiratory transducer, capable of measuring RR and reducing artefact by the subjective responses of alert children. The centile charts will be helpful as an aid to detecting abnormal RR in children and will contribute to further systematic reviews related to this vital sign.
REVIEW | doi:10.20944/preprints202001.0256.v1
Online: 22 January 2020 (09:24:53 CET)
Pompe disease is a glycogen storage disease caused by a deficiency in acid α-glucosidase (GAA) – a hydrolase necessary for the degradation of lysosomal glycogen. This deficiency in GAA results in muscle and neuronal glycogen accumulation, which causes respiratory insufficiency. Pompe disease rodent models provide a means of assessing respiratory pathology and are important for pre-clinical studies of novel therapies that aim to treat respiratory dysfunction and improve quality of life. This review aims to compile and summarize existing manuscripts which characterize the respiratory phenotype of Pompe rodent models. Manuscripts included in this review were selected utilizing specific search terms and exclusion criteria. Analysis of these findings demonstrate that Pompe disease rodent models have respiratory physiological defects as well as pathologies in the diaphragm, tongue, phrenic and hypoglossal motor nucleus, phrenic and hypoglossal nerves, neuromuscular junctions, and airway smooth muscle and higher order respiratory control centers. Overall, the culmination of these pathologies contributes to severe respiratory dysfunction, underscoring the importance of characterizing the respiratory phenotype while developing effective therapies for patients.
ARTICLE | doi:10.20944/preprints202106.0173.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: Fade abruptly, abnormal respiratory noise, dynamic overground endoscopy, upper respiratory tract, horse.
Online: 7 June 2021 (12:41:43 CEST)
The purpose of the study was to find the source of complaints and to diagnose dynamic upper respiratory tract problems, which were derived from the horse owners, trainers, and jockeys, and to evaluate the overground endoscopic examination efficiency to determine the subclinical upper respiratory tract (URT) abnormalities, which were unable to diagnose with resting endoscopy. In the study, overground endoscopy has been used which nowadays there is a more useful and safe technique of performing endoscopy during ridden exercise in the natural field to diagnose dynamic upper respiratory tract (URT) abnormalities in comparison with the more traditional method of resting endoscopy. This study focused on 25 racehorses (Thoroughbred, n:22 and Arabian n: 3), which were admitted to Racehorse Hospital with complaints of fade abruptly and/or abnormal respiratory noise during the last meters of the race. All horses were examined for the complaints to be associated with systemic disorders and/or lameness, the racehorses with lameness and/or systemic disorders findings were excluded. Resting (post-exercise) and overground endoscopy by using Dr. Fritz® ETL-Equine Overground Endoscopy was performed on a polytrack racecourse in all racehorses. Observed abnormalities were recorded as simple and complex cases and the results of resting and dynamic examination were compared. It was concluded the overground endoscopic examination has a useful diagnostic value in determining the cause of abnormal respiratory noise and/or fade abruptly.
REVIEW | doi:10.20944/preprints202004.0467.v1
Subject: Life Sciences, Biotechnology Keywords: respiratory acidosis; CO2 narcosis; acute respiratory distress syndrome; hyperoxia; unexplained physiological event
Online: 26 April 2020 (03:26:09 CEST)
Over the last 20 years, there has been a significant increase in the number of unexplained physiological events (UPEs) reported by pilots of fighter jets across different fleets. The UPEs have resulted in grounding some types of aircraft, loss of airplanes, and even loss of life. Despite considerable research, no single agreed-upon root cause has been found that explains UPEs, and therefore no reliable corrective actions exist. The purpose of this review was to analyze the literature related to other industries in which artificial hyperoxic gas mixes are employed and similar adverse reports have been reported. Based on analysis of the literature, it is hypothesized that UPEs are caused by unlimited delivery of high-dose oxygen in excess of officially approved oxygen schedules in the presence of inadequate airflow rates, at a time when the positive pressure breathing feature of their oxygen regulator system is not used. During flight maneuvers such as climbs, turns, and descents, pulmonary vital capacity is impaired by G-maneuvers and oxygen- and G-induced atelectasis. At the same time, tidal volume is reduced by flight gear, and effective gas exchange is not supported by adequate ventilation. These factors combine to produce hypercarbia, respiratory acidosis, acute respiratory distress syndrome, CO2 narcosis, and coma. In fact, reports from field data related to incidents in F-18S/H, showing that emergency oxygen did not correct the hypoxia-like symptoms including long-lasting periods of incapacitation and prolonged headaches, lend support to this hypothesis.
REVIEW | doi:10.20944/preprints202101.0575.v1
Subject: Medicine & Pharmacology, Allergology Keywords: wearable respiratory monitors; smart garment; lung volume; respiratory inductance plethysmography; chest expansion; inhalation topography
Online: 27 January 2021 (21:27:53 CET)
Background: Natural environment inhalation topography provides useful information for toxicant exposure, risk assessment and cardiopulmonary performance. Commercially available Wearable Respiratory Monitors (WRM), which are currently used to measure a variety of physiological parameters such as heart rate and breathing frequency, can be leveraged to obtain inhalation topography, yet little work has been done. This paper assesses the feasibility of adapting these WRMs for measuring inhalation topography. Methods: Commercially available WRMs were compiled and assessed for the ability to report chest motion, data analysis software features, ambulatory observation capabilities, participant acceptability, purchasing constraints and affordability. Results: The following WRMs were found: LifeShirt, Equivital EQ02 LifeMonitor, Smartex WWS, Hexoskin Smart Garment, Zephyr BioHarness, Nox T3&A1, BioRadio, SleepSense Inductance Band, and ezRIP & zRIP Durabelt. None of the WRMs satisfied all six assessment criteria in a manner enabling them to be used for inhalation topography without modification and development. Conclusion: The results indicate that there are WRMs with core technologies and characteristics that can be built upon for ambulatory inhalation topography measurement in the NE.
REVIEW | doi:10.20944/preprints202004.0330.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2 (CoV-2); COVID-19; coronavirus; pandemic; respiratory distress; brainstem; respiratory center
Online: 19 April 2020 (05:37:30 CEST)
Covid-19 pandemic has captivated scientists to investigate if this new disease can affect the central nervous system (CNS). The most challenging symptoms of Covid-19 are related to respiratory distress, and most patients admitted in intensive care units cannot breathe by their own. Therefore, a crucial question is if respiratory distress can be partially explained by the CNS affection. SARS-Cov-2 is a beta-coronavirus that shares high similarities with SARS-CoV. The infection of SARS‐CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Those coronaviruses have been able to invade the brainstem via a synapse‐connected route to the medullary respiratory center, where the infected regions included the nucleus of the solitary tract and nucleus ambiguous. The vagal afferent nerves from receptors in the lung communicate with the medulla and pons respiratory control centers to coordinate inspiration and expiration. This suggests that neuroinvasion of SARS‐CoV‐2 might play a role in the acute respiratory failure of Covid-19. Therefore, acute respiratory distress in Covid-19 can be partially explained by brainstem dysfunction, suggesting the needs of more specific and aggressive treatments with the direct participation of neurologists and neurointensivists.
ARTICLE | doi:10.20944/preprints202204.0105.v1
Online: 12 April 2022 (08:49:09 CEST)
OBJETIVES: During the COVID-19 pandemic, the risk of collapse of the health system created great difficulties. We will demonstrate that Intermediate Respiratory Care Units (IRCU) provide adequate management of patients with non-invasive respiratory support, which is particularly important in patients with SARS-CoV-2 pneumonia. METHODS: A prospective observational study of patients with COVID-19 admitted to the ICU of a tertiary hospital. Sociodemographic data, comorbidities, pharmacological, respiratory support, laboratory and blood gas variables were collected. The overall cost of the unit was subsequently analyzed. RESULTS: 991 patients were admitted, 56 to the IRCU (of the 81 a critical care unit). Mean age was 65 years (SD 12.8), Barthel Index 75 (SD 8.3), Charlson 3.1 (SD 2.2), HTN 27%, COPD 89% and obesity 24%. Significant relationship (p <0.05) with higher mortality of the following: fever greater than or equal to 39oC [OR 5.6; 95% CI (1.2-2.7); p = 0.020], protocolized pharmacological treatment [OR 0.3; 95% CI (0.1-0.9); p = 0.023] and IOI [OR 3.7; 95% CI (1.1-12.3); p = 0.025]. NIMV showed less of a negative impact [OR 1.8; 95% CI (0.4-8.4); p = 0.423] than IOI. The total cost of the IRCUs amounted to €66,233. The cost per day of stay in the IRCU was €164 per patient. The total cost avoided was €214,865. CONCLUSION: The pandemic has highlighted the importance of IRCUs in facilitating the management of a high patient volume. The treatment carried out in IRCUs is effective and efficient, reducing both admissions to and stays in the ICU.
Subject: Life Sciences, Biotechnology Keywords: metabolic flexibility, respiratory quotient, energy expenditure
Online: 24 May 2021 (13:48:29 CEST)
Metabolic flexibility is the ability of an organism to adapt its energy source based on nutrient availability and energy requirements. In humans, this ability has been linked to cardio-metabolic health and healthy aging. Genome-scale metabolic models have been employed to simulate metabolic flexibility by computing the Respiratory Quotient (RQ), which is defined as the ratio of carbon dioxide produced to oxygen consumed, and varies between values of 0.7 for pure fat metabolism and 1.0 for pure carbohydrate metabolism. While the nutritional determinants of metabolic flexibility are known, the role of low energy expenditure and sedentary behavior in the development of metabolic inflexibility is less studied. In this study we present a new description of metabolic flexibility in genome-scale metabolic models which accounts for energy expenditure, and we study the interactions between physical activity and nutrition in a set of patient-derived models of skeletal muscle metabolism in older adults. The simulations show that fuel choice is sensitive to ATP consumption rate in all models tested. The ability to adapt fuel utilization to energy demands is an intrinsic property of the metabolic network
ARTICLE | doi:10.20944/preprints202105.0345.v1
Subject: Materials Science, Biomaterials Keywords: Respiratory Failure; COVID19; Intravenous Immunoglobulin Therapy
Online: 14 May 2021 (15:04:29 CEST)
Adjunctive therapy with polyclonal intravenous immunoglobins (IVIg) is currently used for preventing or managing infections and sepsis, especially in immunocompromised patients. The pathobiology of COVID19 and the mechanisms of action of Ig led to consider this adjunctive therapy also in patients with respiratory failure by SARS-CoV2 infection. This manuscript report the rationale, the available data and the results of a structured consensus on intravenous Ig therapy in patients with severe COVID19. METHODS A panel of multidisciplinary experts defined the clinical phenotypes of COVID19 patients with severe respiratory failure and, after literature review, voted for the agreement on the rationale and the potential role of IVIg therapy for each phenotype. Due to the scarce evidence available, a modified RAND/UCLA appropriateness method was used. RESULTS Three different phenotypes of COVID19 patients with severe respiratory failure were identified: patients with an abrupt and dysregulated hyperinflammatory response (early phase), patients with suspected immune-paralysis (late phase), and patients with sepsis by hospital-acquired superinfection (sepsis by bacterial superinfection). The rationale for intravenous Ig therapy in the early phase was considered uncertain whereas the panellists considered appropriate its use in the late phase and patients with sepsis/septic shock by bacterial superinfection. CONCLUSION As with other immunotherapies, IVIg adjunctive therapy may a potential role in the managing of COVID19 patients. The ongoing trials will clarify the appropriate target population and the true effectiveness.
REVIEW | doi:10.20944/preprints202006.0074.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: COVID-19; myasthenia gravis; respiratory management
Online: 7 June 2020 (09:28:09 CEST)
The outbreak of COVID-19 has brought unprecedented risks and challenges to everyone in the world. Myasthenia gravis is an autoimmune disease of the nervous system. Infection can worsen it and cause severe symptoms such as myasthenia crisis and respiratory failure. At present, the pandemic of COVID-19 may promote the aggravation of patients with MG. This article focuses on the respiratory management of MG patients during the epidemic of COVID-19.
BRIEF REPORT | doi:10.20944/preprints202004.0452.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: respiratory failure; stethoscope; ultrasound; COVID-19
Online: 25 April 2020 (02:31:18 CEST)
The current Covid-19 pandemic has hugely disrupted the delivery of routine and established medical care. Patients can develop a wide range of clinical signs and symptoms from a cough and fever to severe respiratory failure. There is an ongoing argument on a concise investigative pathway to ensure the safety of all healthcare workers. The stethoscope can help with any clinical respiratory assessment but the risk of cross infection is high. Computer tomography should not be routinely performed. There is a potential place for lung ultrasound but outcomes are not yet determined.
HYPOTHESIS | doi:10.20944/preprints202004.0317.v2
Subject: Keywords: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); COVID19; Middle East Respiratory Syndrome Coronavirus; bioaerosol; aerosol
Online: 30 April 2020 (05:30:30 CEST)
A short review of the important studies was conducted to evaluate the potential of aerosol transmission of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The minimum size of droplets potentially carrying the SARS-CoV-2 was newly estimated and discussed in this review.
ARTICLE | doi:10.20944/preprints202207.0331.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; diagnose; primary care; respiratory disease
Online: 22 July 2022 (03:12:31 CEST)
Objective: Several authors have analyzed the impact of the pandemic on the incidence rates of different conditions. Our aim was to analyze the impact of the COVID-19 pandemic on primary care new diagnoses of respiratory diseases. Methods: This was an observational retrospective study performed to describe the impact of COVID-19 pandemic on primary care new diagnosis of respiratory diseases other than lung cancer. Incidence rate ratio between pre-pandemic and pandemic period was calculated. Results: We found an decrease in the incidence of respiratory conditions (IRR 0.65) during the pandemic period. When we compared the different groups of diseases according to ICD-10, we found a significant decrease in the number of new cases during the pandemic period, except in the case of pulmonary tuberculosis, abscesses or necrosis of the lungs and other respiratory complications. Instead, we found increases in new diagnoses of flu and pneumonia (IRR 2.17) and respiratory interstitial diseases (IRR 1.41). Conclusion: There has been a decrease in new diagnosis of most respiratory diseases during the COVID-19 pandemic. The real clinical impact of this situation is still unknown. Large-scale real-life studies will make it possible to evaluate the long-term true impact of COVID-19 pandemic on the respiratory diseases management.
REVIEW | doi:10.20944/preprints202108.0082.v1
Subject: Biology, Anatomy & Morphology Keywords: vaccines; vaccination; bovine respiratory disease; antigen; adjuvants
Online: 3 August 2021 (13:39:11 CEST)
Vaccination is widely regarded as a cornerstone in animal or herd health and infectious disease management. Nineteen vaccines against the major pathogens implicated in bovine respiratory disease are registered for use in the UK by the Veterinary Medicines Directorate (VMD). However, despite annual prophylactic vaccination, bovine respiratory disease is still conservatively estimated to cost the UK economy approximately £80 million per annum. This review examines the vaccine types available, discusses the surrounding literature and scientific rationale of the limitations and assesses the potential of novel vaccine technologies.
ARTICLE | doi:10.20944/preprints202103.0602.v2
Subject: Medicine & Pharmacology, Allergology Keywords: COVID-19; hospitalization period; respiratory disease; Hormozgan
Online: 10 May 2021 (12:34:09 CEST)
Abstract Introduction: COVID-19 has a relationship with patients’ demographic characteristics as well as their underlying diseases. This research has been conducted to evaluate factors' effect on Covid-19 patient's hospitalization rate and period in Hormozgan, Iran. Materials and Methods: The inclusion criteria of this retrospective study included all patients diagnosed as COVID-19 Patients after PCR who were referred to Covid-19 hospitals from February 2020 to June 2020 in Hormozgan province, Iran. After the completion of the consent form and observing ethical principles, 3480 patients' information was collected through the interview by Medical care monitoring center unit experts. The checklist was designed according to COVID-19 guidelines and approved by the World Health Organization and Iran Ministry of Health and Medical Education. The studied variables included gender, age, patients’ residence place, smoking history and medications use history, pregnancy, referral type to hospital, contact history with COVID-19 patients, early symptoms, gastrointestinal symptoms, intubation, Po2 level, history of cancer, chronic liver diseases, diabetes, chronic blood diseases, HIV/AIDS, acquired or congenital immunodeficiency, cardiovascular diseases, chronic kidney diseases, dialysis status, asthma and other chronic lung diseases, and chronic neurological disorders. These data were analyzed using descriptive (average-standard deviation-percentage) and analytical (including Chi-square, t-test, and regression tests) statistics with SPSS Ver.23 software. Results: In this study, 3480 COVID-19 patients including 1852 male patients (53.20%) with a median age of 43.11±21.72 and 1628 female patients (46/80%) with a median age of 44.86±22.40. The median age of men was significantly lower than the women's median age (P= 0.02). The duration of hospitalization of male and female patients was reported 2.64±4.14 and 2.76±4.297, respectively which was not statistically significant. The death rate of patients in our study was 6.6%. Conclusion: The results of this study also showed that the hospitalization period of HIV-positive patients and patients with cardiovascular and pulmonary diseases is much longer than other people, which imposes many human and financial costs on the country's health care system. Therefore, to maintain individual health and help improve the critical condition of the virus, it is better to develop and apply stricter protocols to prevent further outbreaks of the disease and check underlying diseases of people suspected to have Covid-19. These results can improve health care system planning and improving medical services presented to covid-19 patients.
REVIEW | doi:10.20944/preprints202006.0045.v1
Subject: Medicine & Pharmacology, Other Keywords: ARDS; COVID-19; Berlin Criteria; Respiratory Failure
Online: 5 June 2020 (13:54:36 CEST)
Introduction: The exponential growth of the SARS-CoV-2 virus transmission during the first months of 2020 has placed substantial pressure on health systems worldwide. The complications derived from the novel coronavirus disease (COVID-19) vary in due to comorbidities, sex and age, with more than 50% of the patients who require some level of intensive care developing acute respiratory distress syndrome (ARDS). Areas covered: Various complications caused by SARS-CoV-2 infection have been identified, the most lethal being the acute respiratory distress syndrome, caused most likely by the presence of severe immune cell response and the concomitant alveolus inflammation. The authors carried out an extensive and comprehensive literature review on SARS-CoV-2 infection, the clinical, pathological and radiological presentation as well as the current treatment strategies. Expert Opinion Elevation of inflammatory biomarkers is a common trend among seriously ill patients. The information available strongly suggests that in COVID-19 patients, their altered immune response, including a massive cytokine storm, is responsible for the further damage evidenced among ARDS patients. The increasingly high number of scientific articles and evidence available can only suggest that the individualization of each case is the norm, not all patients with acute respiratory failure due to COVID-19 meet the Berlin definition and therefore ARDS should be considered as a heterogeneous disease, with a wide range in the expression of its severity and clinical manifestations.
REVIEW | doi:10.20944/preprints201810.0002.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: Probiotics, Upper Respiratory Infections, Network Meta-Analysis
Online: 1 October 2018 (10:22:49 CEST)
Background. Upper respiratory infections (URIs) remains as significant cause of morbidity in children. Evidence on efficacy of probiotics to prevent URIs in children is increasing. This systematic review was assembled to analyze evidence about the efficacy of probiotics to reduce duration of upper respiratory infections in ambulatory children. Methods. Randomized controlled trials (RCTs) comparing probiotics vs. placebo to prevent URIs, published between 2001 and 2016 were considered. Quality evaluation was evaluated using CONSORT. Standard mean difference (SMD) or risk ratio (RR) was calculated. Network Meta-Analysis (NMA), using a random effect model was assembled. Results. 31 RCTs were evaluated and 20 studies were included with 3,635 children randomized to probiotics and 3,433 to placebo. Lactobacillus reuteri [SMD -0.56 CI95% (-0.72 to -0.41), p 0.0001] and Lactobacillus acidophillus [SMD -0.33 CI95% (-0.60 to -0.06), p 0.01] were superior to placebo to reduce duration of URIs. L. rhamnosus GG showed tendency [SMD -0.14 CI95% (-0.28 to 0.0), p 0.048]. On the network forest plot L. reuteri showed preventive equivalence when was compared to L. rhamnosus GG, L. casei and BB12. Conclusions. Lactobacillus reuteri, Lactobacillus rhamnosus GG and Bifidobacterium BB12 are evidence-based alternatives to be considered to prevent URIs in children.
Subject: Biology, Anatomy & Morphology Keywords: Bovine respiratory disease; Pasteurella multocida; resistance; tolerance; satP.
Online: 20 July 2021 (14:48:06 CEST)
Under the pressure of fluoroquinolones, Pasteurella multocida (PM) can easily develop resistance to fluoroquinolones mediated by QRDR target mutation. It is imperative to find new drug resistance inhibitor targets to combat the rapid development of drug resistance. In order to overcome these problems, we sequenced the transcriptome of PM with different levels of resistance to ENR(0.03 μg/mL; 8 μg/mL; 32μg/Ml, Enrofloxacin). The results showed that with the increase of resistance to fluoroquinolones, the expression of satP gene was significantly up-regulated. The satP gene deletion strain and replenishment strain were constructed, and their drug resistance and tolerance were determined. The results showed that the deletion of satP gene did not affect the resistance of PM to fluoroquinolones, rather affected the time when PM developed resistance to fluoroquinolones. After 10 generations of drug induction, the MIC (minimum inhibitory concentration) of fluoroquinolones for wild strain was 64 μg/mL, while the MIC for satP gene deletion strain was only 8 μg/mL. The MDK99 test (time to kill 99% bacteria),agar diffusion test and mutation frequency test showed that the tolerance of satP gene deletion strain was significantly lower than that of wild strain. At the same time, the virulence of gene deletion strain and wild strain was tested, and about 400 times decreased virulence was observed for satP gene deletion strain. The mouse infection model confirmed that mice infected with satP gene deletion strains were more likely to be treated with ENR than mice infected with wild-type bovine PM strains. The results show that satP has potential to be a target of fluoroquinolone resistance inhibitors.
ARTICLE | doi:10.20944/preprints202106.0630.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Exercise; Runners; Near-infrared spectroscopy; Respiratory muscles; Respiration.
Online: 28 June 2021 (09:44:55 CEST)
The study aimed to evaluate the association between the changes in ventilatory variables (tidal volume (Vt), respiratory rate (RR), and lung ventilation (VE)) and deoxygenation of m.intescostales (∆SmO2-m.intercostales) during a maximal incremental exercise in nineteen male competitive marathon runners. The ventilatory variables and oxygen-consumption (VO2) were recorded breath-by-breath by exhaled gas analysis. A near-infrared spectroscopy device (MOXY) located in the right-hemithorax allowed recording SmO2-m.intercostales. To explore changes in oxygen levels in muscles with high demand during exercise, a second MOXY records SmO2-m.vastus laterallis. The triphasic model of exercise intensity was used for evaluating changes in SmO2 in both muscle groups. We found that ∆SmO2-m.intercostales correlated with VO2-peak (r=0.65; p=0.002) and the increase of VE (r=0.78; p=0.001), RR (r=0.54; p=0.001), but not Vt (p=0.210). The interaction of factors (muscles X exercise-phases) in SmO2 expressed as an arbitrary unit (a.u) was significant (p=0.005). At VT1 were no difference (p=0.177), but SmO2-m.intercostales was higher at VT1 (p<0.001) and VO2-peak (p<0.001). In competitive marathon runners, the m.intercostales deoxygenation during incremental exercise is directly associated with the aerobic capacity and increased lung ventilation and respiratory rate, but not tidal volume. Besides, it shows less deoxygenation than m.vastus laterallis at intensities above the aerobic ventilatory threshold.
ARTICLE | doi:10.20944/preprints202005.0216.v1
Subject: Keywords: children; infectious disease; lower respiratory tract infections; gastrointestinal
Online: 12 May 2020 (12:59:25 CEST)
The objective of this study was to describe the overall pattern of morbidity and mortality of children seen at the Thai Binh Pediatric Hospital in Vietnam, with a focus on infectious diseases. A retrospective review of hospitalisation records was conducted from 1 January 2015 to 31 December 2019. Data were obtained from a total of 113,999 records. The median age of patients was 18 months, with 83.98% of patients aged <5 years. Infectious diseases accounted for 61.0% of all cases. The most prevalent diseases were lower respiratory tract infections (32.8%), followed by gastrointestinal infections (13.3%) and confirmed influenza (5.4%). Most infections were not microbiologically documented. A total of 81.4% patients received at least one antibiotic. Most patients (97.0%) were hospitalised for less than 15 days. Regarding outcomes, 87.8% patients were discharged home with a favourable outcome. 12.0% were transferred to the Vietnam National Children’s Hospital because their condition had worsened and 0.1% died. In total, infectious diseases accounted for 40.4% of deaths, followed by neonatal disorders (34.6%). Our data serves a basis for the identification of needs for diagnostic tools and for future evaluation of the effect of the targeted implementation of such facilities. Point-of-care tests, including real-time PCR assays to identify common pathogens should be implemented for more accurate diagnosis and more appropriate antibiotic use.
ARTICLE | doi:10.20944/preprints201808.0435.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Respiratory tract infections (RTI); antibiotic; sensitivity; resistant; bacteria
Online: 24 August 2018 (11:46:41 CEST)
1) Background: Respiratory tract infections (RTI) has been known to be a significant health concern for mortality and morbidity since many years. This study was aimed at determining the prevalence of bacterial pathogen causing upper respiratory tract (URTIs) and the susceptibility patterns to frequently used antibiotics among patients attending Abusetta hospital in Tripoli district; 2) Methods: A total of 1,110 throat swabs were collected between Jan, 2011 to December, 2014 and inoculated onto Blood agar, MacCkonkey agar and Chocolate agar then incubated at 37 oC for 24 hours. Bacterial pathogens were determined by bacteriological culture methods and antibiotic susceptibility of the isolates was identified following Clinical Laboratory Standard Institute guidelines (CLSI); 3) Results: Of the 1,110 respiratory samples tested, 71.1% (n = 789) of specimens were positive cultures with the dominant bacterial pathogens being streptococcus pneumonia 43.3% (n = 342), followed by pseudomonas aeruginosa 22.8% (n = 180), staphylococcus aurous 13.8% (n = 109), Escherichia Coli 6.9% (n = 55), Enterobacter spp 6.2% (n = 49), Citrobacter 4.5% (n = 36), and Klebsiella 2.2% (n = 18). Most isolates exhibited resistance against the commonly used antibiotics and to at least one antibiotic; and 4) Conclusions: The level of antibiotic resistance in this study is alarming and brings to light the timely and suitable diagnosis of the common bacteria causes of URTIs and proper antibiotic administration based on susceptibility test.
ARTICLE | doi:10.20944/preprints201808.0318.v1
Subject: Life Sciences, Virology Keywords: respiratory syncytial virus; phylogenetics; evolution; multi-year persistence
Online: 18 August 2018 (05:14:42 CEST)
There is an ongoing global pandemic of human respiratory syncytial virus (RSV) infection that results in substantial annual morbidity and mortality. In Australia, RSV is the major cause of acute lower respiratory tract infections (ALRI). Nevertheless, little is known about the extent and origins of genetic diversity of RSV in Australia, nor the factors that shape this diversity. We conducted a genome-scale analysis of RSV infections in New South Wales (NSW). RSV genomes were successfully sequenced for 144 specimens collected between 2010-2016. Of these, 64 belonged to the RSVA and 80 to the RSVB subtype. Phylogenetic analysis revealed a wide diversity of RSV lineages within NSW and that both subtypes evolved rapidly in a strongly clock-like manner, with mean rates of approximately 6-8 x 10-4 nucleotide substitutions per site per year. There was only weak evidence for geographic clustering of sequences, indicative of fluid patterns of transmission within the infected population, and no evidence of any clustering by patient age such that viruses in the same lineages circulate through the entire host population. Importantly, we show that both subtypes circulated concurrently in NSW with multiple introductions into the Australian population in each year, and only limited evidence for multi-year persistence.
ARTICLE | doi:10.20944/preprints201610.0030.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: respiratory symptoms; PM exposure; residential location; Namibia; Windhoek
Online: 10 October 2016 (09:59:29 CEST)
The study aimed to estimate the prevalence of respiratory symptoms and to assess respiratory health risks associated with Particulate Matter (PM) exposure among the residents of Windhoek, Namibia. Objectives: To measure particulate pollution concentration in Windhoek through monitoring of particulate matter concentration and to identify any associations between particulate pollution, individual location and respiratory health among the Windhoek resident’s. Methods: an adapted standardized self-administered questionnaire was used to collect respiratory health related data as well as previous exposure, while PM monitoring was done using ASTM D1739 reference method. Results: A high prevalence was observed for cough (43%), breathlessness (25%), and Asthma (11.2%). PM was found to be a significant risk factor for episode of cough and phlegm, while high PM exposure category had increased odds ratio for episode of phlegm and cough (OR: 2.5, 95% CI: 0.8-8.0). No association was observed between location and respiratory health outcomes. Conclusion: The study found high levels of PM concentration across all Windhoek suburbs which were above the German, American and EPA. Enactment of legislation relating to the control and monitoring of PM related emissions at point of generation is required at country and city level.
ARTICLE | doi:10.20944/preprints202112.0128.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: ECMO; ECLS; ECCO2R; ARDS; respiratory failure, LTx, DIN EN ISO 7199; Extracorporeal membrane oxygenation, acute respiratory distress syndrome, animal model
Online: 8 December 2021 (14:16:25 CET)
Extracorporeal membrane oxygenation (ECMO) is an established rescue therapy for patients with chronic respiratory failure waiting for lung transplantation (LTx). The therapy inherent immobilization may result in fatigue, consecutive deteriorated prognosis and even lost eligibility for transplantation. We conducted a feasibility study on a novel system designed for the deployment of a mobile ECMO device, enabling physical exercise of awake patients prior to LTx. The system comprises a novel mobile oxygenator with a directly connected blood pump, a double lumen cannula, gas blender and supply, as well as control, and energy management. In-vitro experiments included tests regarding performance, efficiency, and blood damage. A reduced system was tested in vivo for feasibility using a novel large animal model. Six anesthetized pigs were first positioned in supine position, followed by a 45° angle, simulating an upright position of the patients. We monitored performance and vital parameters. All in-vitro experiments showed good performance for the respective subsystems and the integrated system. The acute invivo trials of 8h duration confirmed the results. The novel mobile ECMO-system enables adequate oxygenation and decarboxylation sufficient for, e.g., physical exercise of designated LTx-recipients. These results are promising and suggest further preclinical studies on safety and efficacy to facilitate translation into clinical application.
REVIEW | doi:10.20944/preprints202103.0597.v2
Subject: Medicine & Pharmacology, Allergology Keywords: viral respiratory infections; severe asthma; immune response; biologicals; omalizumab
Online: 26 March 2021 (10:55:06 CET)
Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although very limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which is able to stabilize the effector cells becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allows a great improvement in the management of asthma.
ARTICLE | doi:10.20944/preprints201804.0375.v1
Subject: Medicine & Pharmacology, Other Keywords: pesticides; spirometry; respiratory symptoms; cholinesterase; rural workers; family farmers
Online: 29 April 2018 (10:25:38 CEST)
Pesticide exposure is a growing concern for public health. Although Brazil is the world's largest consumer of pesticides, few studies addressed the health effects among farmers. This study aimed to evaluate whether pesticide exposure is associated with respiratory outcomes among rural workers and relatives in Brazil during the crop and off-seasons. 82 family farmers were interviewed about occupational history and respiratory symptoms, and cholinesterase tests were conducted in the crop-season. Spirometry was performed during the crop and off-season. Respiratory outcomes were compared between seasons and multiple regressions were conducted to search for associations with exposure indicators. Participants were occupationally and environmentally exposed to multiple pesticides from an early age. During the crop and off-season, respectively, they presented a prevalence of 40% and 30.7% for cough, 30.7% and 24% for nasal allergies, and 24% and 17.3% for chest tightness. Significant relations between spirometry impairments and exposure indicators were found both during the crop and off-season. These findings provide complementary evidence about the association of pesticide exposure with adverse respiratory effects among family farmers in Brazil. This situation requires special attention as it may increase the risk of pulmonary dysfunctions, and the morbidity and mortality burden associated with these diseases.
REVIEW | doi:10.20944/preprints202104.0633.v2
Subject: Medicine & Pharmacology, General Medical Research Keywords: viral transmission; causation; evidence hierarchy; SARS-CoV-2; respiratory pathogens
Online: 30 June 2022 (03:33:13 CEST)
Systematic reviews of 591 primary studies of the modes of transmission for SARS-CoV-2 show significant methodological shortcomings and heterogeneity in the design, conduct, testing and reporting of SARS-CoV-2 transmission. While this is partly understandable at the outset of a pandemic, evidence rules of proof for assessing the transmission of this virus are needed for pre-sent and future pandemics of viral respiratory pathogens. We review the history of causality as-sessment related to microbial etiologies with a focus on respiratory viruses and suggest a hierar-chy of evidence to integrate clinical, epidemiologic, molecular and laboratory perspectives on transmission. The hierarchy, if applied to future studies, should narrow the uncertainty over the twin concepts of causality and transmission of human respiratory viruses. We attempt to address the translational gap between the current research evidence and the assessment of causality in the transmission of respiratory viruses with a focus on SARS-CoV-2. Experimentation, consistency and independent replication of research alongside our proposed framework provide a chain of evidence that can reduce the uncertainty over the transmission of respiratory viruses and increase the level of confidence in specific modes of transmission, informing the measures that should be undertaken to prevent transmission.
ARTICLE | doi:10.20944/preprints202203.0187.v2
Subject: Life Sciences, Virology Keywords: human parechovirus; HPeV; PeV-A; Panama; gastrointestinal infection; respiratory infection
Online: 27 April 2022 (08:07:52 CEST)
Human Parechoviruses, officially known as Parechovirus A (PeV-A), is associated with mild gastrointestinal and respiratory illness in young children, however, they may also give rise to Central Nervous System (CNS) infections and neonatal sepsis. While studies have delved into the detection of PeV-A in different populations, the detection of PeV-A in Hispanic populations in Latin American countries is not well-known. The aim of this study was to determine the presence of PeV-A in respiratory, gastrointestinal, and neurological clinical samples of pediatric patients in Panama. Two hundred samples of pediatric patients with a negative diagnosis for the main respiratory viruses, rotavirus and neurological viruses such as herpesvirus, enterovirus and cytomegalovirus, collected between 2014 and 2015, were analyzed by real-time RT-PCR. Eight positive PeV-A infections were detected, 2 in respiratory samples, 5 in stool samples and one detected in cerebrospinal fluid. This is the fisrt report of PeV-A in Panamá.
ARTICLE | doi:10.20944/preprints202110.0094.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: nutrition; pediatrics; geographic information systems; acute respiratory infections; diarrhea; growth
Online: 6 October 2021 (09:00:12 CEST)
Infectious disease is the leading cause of mortality in children under five. This study has investigated environmental factors related to the morbidity of acute respiratory infections (ARIs), diarrhea, and growth using geographical information systems (GIS) technology. Anthropometric, address and disease prevalence data were collected through the SEEM study in Matiari, Pakistan. Publicly available map data was used to compile coordinates of healthcare facilities. A Pearson correlation coefficient (r) was used to calculate the correlation between distance from healthcare facilities and participant growth and morbidity. Other continuous variables influencing these outcomes were analyzed using a random forest regression model. In this study of 416 children, we found participants living closer to secondary hospitals had lower prevalence of ARI (r=0.154, p<0.010) and diarrhea (r=0.228, p<0.001) as well as participants living closer to Maternal Health Centers (MHCs): ARI (r=0.185, p<0.002) and diarrhea (r=0.223, p<0.001) compared to those living near primary facilities. Our random forest model showed distance to have high variable importance in the context of disease prevalence. Our results indicated that participants closer to more basic healthcare facilities reported a higher prevalence of both diarrhea and ARI than those near more urban facilities, highlighting potential public policy gaps in ameliorating rural health.
ARTICLE | doi:10.20944/preprints202105.0706.v1
Subject: Life Sciences, Biochemistry Keywords: alcohol; brain networks; heart rate variability; abstinence; respiratory sinus arrhythmia
Online: 28 May 2021 (13:45:25 CEST)
Alcohol consumption is now common practice worldwide, and functional brain networks are beginning to reveal the complex interactions observed with alcohol consumption and abstinence. The autonomic nervous system (ANS) has a well-documented relationship with alcohol use, and a growing body of research is finding links between the ANS and functional brain networks. This study recruited everyday drinkers in an effort to uncover the relationship between alcohol abstinence, ANS function, and whole brain functional brain networks. Participants (n=29), 24-60 years-of-age, consumed moderate levels of alcohol regularly (males 2.4 (±0.26) drinks/day, females 2.3 (±0.96) drinks/day). ANS function, specifically cardiac vagal tone, was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (PBRSA). Functional brain networks were generated from resting-state MRI scans obtained following 3-day periods of typical consumption and abstinence. A multi-task mixed-effects regression model determined the influences of HRV and drinking state on functional network connectivity. Results showed differences in the relationship between the strength of network connections and clustering coefficients across drinking states, moderated by PBRSA. Increases in connection strength between highly clustered nodes during abstinence as PBRSA increases demonstrates a greater possible range of topological configurations at high PBRSA values. This novel finding begins to shed light on the complex interactions between typical alcohol abstinence and physiological responses of the central and autonomic nervous system.
ARTICLE | doi:10.20944/preprints202105.0004.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Appeasing Pheromone; Bovine; Respiratory Infections; Immune Response; Average Daily Gain
Online: 3 May 2021 (09:15:45 CEST)
Bovine respiratory disease is still a major concern in feedlots and has major economic impact. Another consequence of respiratory infections is the use of antimicrobial molecules to control bacterial pathogens. This can participate to the emergence and shedding of antimicrobial re-sistance that can threaten animal as well as human health. Appeasing pheromones with their capacity to reduce stress and thus their ability to preserve the functions of the immune system have been proposed to reduce the use of antimicrobial substances. In the current report we as-sessed the effect of appeasing pheromone administration on bovine health and performance during the fattening period. Zootechnical and health parameters as well as whole blood immune transcript expressions were measured over weeks in young bulls to determine the effect of the pheromone. We observed a reduction of clinical signs at day 30 in young bulls who received the pheromone and a higher expression of interleukin 8 transcripts in this group than in the control group. Our results are in line with previous reports in bovine and other mammals and ask for further studies to shed more light on the beneficial impact of appeasing pheromones and to de-cipher their exact mechanisms of action.
ARTICLE | doi:10.20944/preprints202104.0409.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Reflux; Laryngopharyngeal; Clinical; Atypical; Nasal; Otological; Respiratory; Management; Treatment; Diagnosis
Online: 15 April 2021 (12:08:19 CEST)
Background: Laryngopharyngeal reflux (LPR) is a common disease in otolaryngology characterized by an inflammatory reaction of the mucosa of the upper aerodigestive tract caused by digestive refluxate enzymes. LPR has been identified as etiological or favoring factor of laryngeal, oral, sinonasal or otological diseases. In this case-series, we reported atypical clinical presentation of LPR in patients presenting in our clinic with reflux. Methods: A retrospective medical chart review of 351 patients with LPR treated in the European Reflux Clinic in Brussels, Poitiers and Paris was performed. In order to be included, patients had to report atypical clinical presentation of LPR, consisting of symptoms or findings that are not described in reflux symptom score and reflux sign assessment. The LPR diagnosis was confirmed with 24-hour hypopharyngeal-esophageal impedance pH-study and patients were treated with a combination of diet, proton pump inhibitors and alginates. The atypical symptoms or findings had to be resolved from pre- to posttreatment Results: From 2017 to 2021, 21 patients with atypical LPR were treated in our center. The clinical presentation consisted of recurrent aphthosis or burning mouth (N=9), recurrent burps and abdominal disorders (N=2), posterior nasal obstruction (N=2), recurrent acute suppurative otitis media (N=2), severe vocal fold dysplasia (N=2), and recurrent acute rhinopharyngitis (N=1), tearing (N=1), aspirations (N=1) or tracheobronchitis (N=1). Abnormal upper aerodigestive tract reflux events were identified in all of these patients. Atypical clinical findings resolved and did not recur after an adequate anti-reflux treatment. Conclusion: LPR may present with various clinical presentations including mouth, eye, tracheobronchial, nasal or laryngeal findings, which may all regress with an adequate treatment. Future studies are needed to better specify the relationship between LPR and these atypical findings through analyses identifying gastroduodenal enzyme in the enflamed tissue.
ARTICLE | doi:10.20944/preprints202012.0258.v1
Subject: Life Sciences, Biochemistry Keywords: co-infection; SARS-CoV-2; Covid-19; seasonal respiratory viruses
Online: 10 December 2020 (12:53:28 CET)
Background: Co-infections of SARS-CoV-2 with respiratory viruses, bacteria and fungi have been reported to cause a wide range of illness. Objectives: We asses s the prevalence of co-infection of SARS-CoV-2 with seasonal respiratory viruses, document the respiratory viruses detected among individuals tested for SARS-CoV-2, and describe characteristics of individuals with respiratory virus co-infection detected. Methods: Specimens included in this study were submitted as part of routine clinical testing to Public Health Ontario Laboratory from individuals requiring testing for SARS-CoV-2 and/or seasonal respiratory viruses. Results: Co-infection was detected in a smaller proportion (2.5%) of individuals with laboratory confirmed SARS-CoV-2 than those with seasonal respiratory viruses (4.3%); this difference was not significant. Individuals with any respiratory virus co-infection were more likely to be younger than 65 years of age and male than those with single infection. Those with SARS-CoV-2 co-infection manifested mostly mild respiratory symptoms. Conclusions: Findings of this study may not support routine testing for seasonal respiratory viruses among all individuals tested for SARS-CoV-2, as they were rare during the study period nor associated with severe disease. However, testing for seasonal respiratory viruses should be performed in severely ill individuals, in which detection of other viruses may assist with patient management.
CASE REPORT | doi:10.20944/preprints202008.0640.v1
Subject: Medicine & Pharmacology, Other Keywords: VIP; COVID-19; respiratory failure; vasoactive intestinal peptide; aviptadil; ARDS
Online: 28 August 2020 (11:38:23 CEST)
Background: Vasoactive Intestinal Peptide (VIP) is known to bind to and protect the Alveolar Type II cell by blocking replication of the SARS-CoV-2 virus, upregulating surfactant production, blocking apoptosis, and blocking cytokine effects. RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) has been granted Fast Track Designation and is currently in phase 2/3 placebo-controlled trials. FDA has granted Emergency Use IND and Expanded Access Protocol approval for the use of RLF-100 in patients whose comorbidities render them ineligible for inclusion in the ongoing pivotal trial. Methods: This report describes the first 6 patients with Acute Respiratory Failure in Critical COVID-19, enrolled under Emergency Use IND were treated with three successive 12-hour infusions of intravenous Aviptadil at 50/100/150 pmol/kg/hr, while continuing to receive maximal ICU care. Results: Median patient follow-up time is 14 days. So far, all treated patients have survived. Improved radiographic appearance of typical “ground glass” COVID-19 features to varying degrees is seen in all patients within 72 hours. Improvement in blood oxygenation is seen in all patients, with complete remission from respiratory failure in 4 of 6 patients. An average 56% reduction in inflammatory markers was seen, together with a median 4 point reduction in the NIAID Ordinal Scale. 2/6 patients were discharged from the hospital and 1 patient was downgraded to the general medicine floor. Comment: The short term survival of 6/6 patients with respiratory failure in the setting of COVID-19 and major comorbidity is the most dramatic response ever seen with an antiviral agent. Improvement in radiographic appearance, oxygenation requirement, and inflammatory markers is consistent with in vitro evidence of direct anti-viral effect.
BRIEF REPORT | doi:10.20944/preprints202007.0569.v1
Subject: Medicine & Pharmacology, Allergology Keywords: SARS-CoV-2; COVID-19; respiratory failure; ARDS; ventilation; ECMO
Online: 24 July 2020 (04:44:14 CEST)
The rapidly evolving understanding of Coronavirus Disease 2019 (COVID-19) respiratory failure pathogenesis, limited disease-specific evidence and demand-resource imbalances have posed significant challenges for intensive care clinicians. In this single-centre retrospective cohort study we describe the outcomes of COVID-19 patients admitted to Guy’s and St. Thomas’ NHS Foundation Trust (GSTT) critical care service. Patients were managed according to a local respiratory failure management pathway that was predicated on timely invasive ventilation when indicated and tailored ventilatory strategies according to pulmonary mechanics. Between 2nd March and 25th May 2020 GSTT critical care service admitted 316 patients with confirmed COVID-19. Of the 201 patients admitted directly through the Emergency Department with a completed critical care outcome, 71.1% survived to critical care discharge. These favourable outcomes may serve to inform the wider debate on the optimal ventilatory management in COVID-19.
ARTICLE | doi:10.20944/preprints202007.0453.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: ARDS; VIP; Aviptadil; RLF-100; Acute Respiratory Distress Syndrome; Sepsis
Online: 20 July 2020 (03:46:11 CEST)
Purpose: To assess the clinical safety and possible effectiveness of Vasoactive Intestinal Peptide in the treatment of Acute Respiratory Distress Syndrome (ARDS) related to sepsis. Methods: Under FDA Investigational New Drug clearance, 8 patients with ARDS related to sepsis were treated with 50 pmole/kg/hr – 100 pmole/kg/hr of Vasoactive Intestinal Peptide by intravenous infusion for 12 hours. All patients were on mechanical ventilation and full telemetery. Results: No drug-related serious adverse events were seen. Hypotension was seen in association with two infusions and diarrhea in association with one, but did not necessitate cessation of therapy. Bigeminy was seen in association with one infusion without sequelae. Seven of eight patients demonstrated a successful course during intensive care and were successfully removed from mechanical ventilation and discharged from intensive care. The eighth patient succumbed to purulent secretions in the lungs. Of those who were discharged from the ICU, six demonstrated successful 30 day survival. The seventh died from a cerebral infract at day 30, deemed unrelated to treatment with VIP. Serum levels of Tumor Necrosis Factor α were obtained in 6 patients at baseline and 24 hours and were seen to decrease with treatment in five patients. Conclusions: Initial clinical results of treatment with VIP in patients with ARDS demonstrated a safety profile consistent with previous studies in normal volunteers. The successful clinical course seen in 7 of 8 patients in the setting of an expected 50% survival may suggest that VIP shows promise in the treatment of other infectious conditions that damage the pulmonary epithelium, particularly COVID-19.
REVIEW | doi:10.20944/preprints202006.0248.v1
Subject: Life Sciences, Immunology Keywords: probiotic; upper respiratory tract infection (URTI); infection; prevention; common cold
Online: 21 June 2020 (10:07:31 CEST)
Background: Probiotics can provide health benefits to an individual by regulation of the immune system. Many clinical trials have found that probiotics can prevent upper respiratory tracts infections. Aim: To perform a systematic review and meta-analysis of available trials to investigate the effectiveness of probiotics in the prevention of upper respiratory tract infections in individuals of all ages. Conclusion: Probiotics were found to be better in reducing the number of participants who experienced acute URTI, the average duration per episode of acute URTI, use of antibiotics in URTI related cases and absence due to URTI. Side effects were found to be minor, making probiotics a good candidate for clinical use. This shows that probiotics are effective in preventing acute URTIs. However, due to limited studies and small sample size, the results are subjected to bias and should be interpreted with care.
REVIEW | doi:10.20944/preprints202004.0069.v1
Subject: Earth Sciences, Environmental Sciences Keywords: coronavirus; SARS-CoV-2; COVID-19; respiratory diseases; air pollution
Online: 6 April 2020 (15:48:46 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known to cause 2019-coronavirus disease (COVID-19) pandemic is a zoonotic coronavirus and crosses species to infect human populations, where an efficient transmission of virus occurs human-to-human. Nationwide lockdown is being adopted to stop public transport, keep people at their homes and out of their work, and maintain social distancing. In turn, large geographic areas in the world (including China, Italy, Spain, and USA) has been almost halted. This temporary halt is significantly slashing down the air pollution (air pollutants and warming gases) in most cities across the world. This paper: (i) introduces both COVID-19 and air pollution; (ii) overviews the relation of air pollution with respiratory/lung diseases; (iii) compiles and highlights major data appeared in media and journals reporting lowering of air pollution in major cities those have been highly impacted by the COVID-19; and also (iv) lists the way forward in the present context. Because COVID-19 is an ongoing pandemic and currently far from over, strong conclusions could not be drawn with very limited data at present. The temporary slashed down global air pollution as a result of COVID-19 restrictions are expected to stimulate the researchers, policy makers and governments for the judicious use of resources; thereby minimise the global emissions, and maintain their economies once the pandemic eases. On the other, lifting of the nationwide lockdown and eventual normalisation of the temporarily halted sectors may also reverse the currently COVID-19 pandemic-led significantly slashed down global air pollution that could make the future respiratory health crisis grimmer.
ARTICLE | doi:10.20944/preprints201807.0026.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: non-invasive respiratory monitoring; diaphragm motion monitoring; breathing disorder; ultrasound
Online: 3 July 2018 (06:16:35 CEST)
This paper introduces a novel respiratory detection system based on diaphragm wall motion tracking using an embedded ultrasound sensory system. We assess the utility and accuracy of this method in evaluating diaphragmatic function and its contribution to respiratory workload. The developed system is able to monitor the diaphragm wall activities when the sensor is placed in the zone of apposition (ZOA). This system allows the direct measurements with only one ultrasound PZT5 piezo transducer. The system both generates pulsed ultrasound waves at 2.2 MHz and amplifies reflected echoes. According to the diaphragmatic motions, the respiratory signals of the proposed system is insensitive to human motion artifacts. Promising results were obtained from six subjects on six different tests with an average sensitivity and specificity of 84% and 93% of respiration detection, respectively. Measurements are referenced to a SPR-BTA commercial spirometer. In this study, we also evaluated inertial and photoplethysmography (PPG) sensors as other conventional methods in this area.
TECHNICAL NOTE | doi:10.20944/preprints201803.0243.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: respiratory sinus arrhythmia (RSA); R-peak amplitude (RPA); QRS amplitude
Online: 29 March 2018 (05:17:58 CEST)
We propose an electrocardiogram (ECG) signal-based algorithm to estimate the respiratory rate is a significant informative indicator of physiological state of a patient. The consecutive ECG signals reflect the information about the respiration because inhalation and exhalation make transthoracic impedance vary. The proposed algorithm extracts the respiration-related signal by finding out the commonality between the frequency and amplitude features in the ECG pulse train. The respiration rate can be calculated from the principle components after the procedure of the singular spectrum analysis. We achieved 1.7569 breaths per min of root-mean-squared error and 1.7517 of standard deviation with a 32-seconds signal window of the Capnobase dataset, which gives notable improvement compared with the conventional Autoregressive model based estimation methods.
ARTICLE | doi:10.20944/preprints201611.0068.v1
Subject: Earth Sciences, Environmental Sciences Keywords: particulate matter; AirQ model; hospital admission respiratory disease; Athens; Greece
Online: 14 November 2016 (04:13:34 CET)
The main objective of this work is the assessment of the annual number of hospital admissions for respiratory disease (HARD) due to the exposure to in-healable particulate matter (PM10), within the greater Athens area (GAA), Greece. Towards this aim, the time series of the particulate matter with aerodynamic diameter less than 10μm (PM10) recorded in six monitoring stations located in the GAA, for a 13-year period 2001-2013, is used. Initially, a descriptive statistical treatment of PM10 concentrations took place. Furthermore, the AirQ2.2.3 software developed by the WHO was used to evaluate adverse health effects by PM10 in the GAA during the examined period. The results show that, during the examined period PM10 concentrations present a significant decreasing trend. Also, the mean annual HARD cases per 100,000 inhabitants ranged between 20 (suburban location) and 40 (city centre location). Approximately 70% of the annual HARD cases are due to city centre residents. In all examined locations, a declining trend in the annual number of HARD cases is appeared. Moreover, a strong relation between the annual number of HARD cases and the annual number of days exceeding the European Union daily PM10 threshold value was found.
REVIEW | doi:10.20944/preprints202206.0421.v1
Subject: Biology, Other Keywords: Mitochondria; Respiratory chain; Krebs cycle; Succinate; Cancer; Encephalopathy; SDH, SDHI; pesticides
Online: 30 June 2022 (08:31:22 CEST)
Research focused on succinate dehydrogenase (SDH) and its substrate, succinate, culminated in the 50’s accompanying the rapid development of research dedicated to bioenergetics and intermediary metabolism. This allowed to uncover the implication of the SDH in both the mitochondrial respiratory chain and the Krebs cycle. Nowadays this theme is experiencing a real revival following the discovery of the role of SDH and succinate in a subset of tumors and cancers in human. The aim of this review is to enlighten the many questions yet unanswered, ranging from fundamental to clinically oriented aspects, up to the danger of the current use of SDH as a target for a sub class of pesticides.
ARTICLE | doi:10.20944/preprints202201.0118.v2
Subject: Earth Sciences, Environmental Sciences Keywords: spatial heterogeneity; AOD-PM2.5; respiratory-cardiovascular; lag grids; urban-rural; season
Online: 28 March 2022 (13:52:49 CEST)
Optimal use of Hierarchical Bayesian Model (HBM) assembled aerosol optical depth (AOD)-PM2.5 fused surfaces in epidemiologic studies requires homogeneous temporal and spatial fused surfaces. No analytical method is available to evaluate spatial heterogeneity. The temporal case-crossover design was modified to assess the spatial association between four experimental AOD-PM2.5 fused surfaces and four respiratory-cardiovascular hospital events in 12 km2 grids. The maximum number of adjacent lag grids with significant odds ratios (ORs) identified homogeneous spatial areas (HOSAs). The largest HOSA included 5 grids (lag grids 04; 720 km2) and the smallest HOSA contained 2 grids (lag grids 01; 288 km2). Emergency department asthma and inpatient asthma, myocardial infarction, and heart failure ORs were significantly higher in rural grids without air monitors than in urban grids with air monitors at lag grids 0, 1, and 01. Rural grids had higher AOD-PM2.5 concentration levels, population density, and poverty percent than urban grids. Warm season ORs were significantly higher than cold season ORs for all health outcomes at lag grids 0, 1, 01, and 04. The possibility of elevated fine and ultrafine PM and other demographic and environmental risk factors synergistically contributing to elevated respiratory-cardiovascular chronic diseases in persons residing in rural areas was discussed
REVIEW | doi:10.20944/preprints202202.0313.v3
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: seawater; seawater preparation; Aqua Maris; nasal irrigation; upper respiratory track; otorhinolaryngology
Online: 21 March 2022 (09:16:41 CET)
The history of saline nasal irrigation (SNI) is indeed a long one, beginning from the ancient Ayurvedic practices and starting to gain a foothold in the west at the beginning of 20th century. Today, there is a growing number of papers covering effects of SNI from in vitro studies to randomized clinical trials and literature overviews. Based on the recommendations of most of the European and American professional associations, seawater, alone or in combination with other preparations, has its place in treatment of numerous conditions of the upper respiratory tract (URT), primarily in chronic (rhino)sinusitis, allergic rhinitis, acute URT infections and postoperative recovery. Additionally, taking into account its multiple mechanisms of action and mounting evidence from recent studies, locally applied seawater preparations may have an important role in prevention of viral and bacterial infections of the URT. Therefore, in this review we discuss results published in the past years focused on the seawater preparations and their use in clinical and everyday conditions, since such products are superior to saline, have an excellent safety profile and are recommended by most professional associations in the field of otorhinolaryngology.
ARTICLE | doi:10.20944/preprints202108.0090.v1
Subject: Life Sciences, Biochemistry Keywords: Airflow restriction, Physical exercise, Respiratory Muscle Training, Endurance performance, VEGF, EPO
Online: 3 August 2021 (15:04:27 CEST)
Introduction: The Elevation Training Mask 2.0 (ETM) has been introduced as a novel tool to allow for respiratory muscle training and altitude exposure during exercise that can improve performance and hematological markers in elite and well-trained athletes. Thus, the aim of the present study was to assess the effect of wearing ETM while training on erythropoietin (EPO), vascular endothelial growth factor (VEGF), peak oxygen consumption (VO2max), lactate, and 1000-m kayaking performance in elite Kayaking girls. Methods: Thirty elite Kayaking girls (14 to 18-year-old) were equally and randomly assigned into mask, no mask, and control groups. The mask and no-mask groups completed 8 weeks of repeated sprint training, while the control group performed their routine kayaking training programs. Pre- and post-training tests included EPO, VEGF, VO2max, lactate, and 1000-m kayaking performance. Results: 1000-m time trial significantly decreased for mask (p < 0.001) and control (p = 0.035) groups, and was significantly lower in mask group than control (p = 0.014) and no mask (p = 0.009) groups. EPO did not show any significant changes for all groups. VEGF was increased significantly for mask (p = 0.04) and no mask (p = 0.014) groups. Lactate was decreased significantly for mask group (p = 0.025). VO2max increased significantly for no mask group (p = 0.021). Conclusion: Wearing the ETM while participating in 8 weeks of repeated sprint training might improve specific blood markers and endurance performance, especially anaerobic pathways. Performing repeated sprint training while wearing ETM has the potential to enhance performance in Kayak racing.
REVIEW | doi:10.20944/preprints202008.0065.v1
Subject: Life Sciences, Microbiology Keywords: SARS-CoV-2; SARS-CoV; influenza; pneumonia; respiratory tract infectious diseases
Online: 3 August 2020 (08:44:56 CEST)
The short study implicates few basic similarities of COVID-19 such as diseases origination, symptoms, diagnosis with other relatable viral diseases viz SARS-CoV, common Flu, pneumonia etc. In the present situation, other viral diseases are frequently chaotic and misled with COVID-19 disease because of few clinical features similarities in signs and symptoms and also due to lack of specific diagnostic test. To avoid unnecessary suspects, quarantines of false positive results and to prevent the spread of COVID-19 diseases, the scientific technical research field are highly encourage to implement an efficient, rapid and sophisticated superior test for early stages of infection detection. It will be significantly convenient for physician, laboratory technicians and most importantly the common population facing a psychological disturbance.
REVIEW | doi:10.20944/preprints202007.0568.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: SARS-CoV-2; COVID-19; respiratory failure; ARDS; ventilation; MODS; ECMO
Online: 24 July 2020 (04:00:50 CEST)
The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in a significant surge of critically ill patients and an unprecedented demand on intensive care services. The rapidly evolving understanding of pathogenesis, limited disease specific evidence and demand-resource imbalances have posed significant challenges for intensive care clinicians. COVID-19 is a complex multisystem inflammatory vasculopathy with a significant mortality implication for those admitted to intensive care. Institutional strategic preparation and meticulous intensive care support are essential to maximising outcomes during the pandemic. The significant mortality variation observed between institutions and internationally, despite a single aetiology and uniform presentation, highlights the potential influence of management strategies on outcome. Given that optimal organ support and adjunctive therapies for COVID-19 have not yet been well defined by trial-based outcomes, strategies are predicated on existing literature and experiential learning. This review outlines the relevant pathophysiology and management strategies for critically ill patients with COVID-19, and shares some of the collective learning accumulated in a high volume Severe Respiratory Failure centre in London.
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; SARS-CoV-2; coronavirus; severe acute respiratory syndrome coronavirus
Online: 5 July 2020 (10:16:43 CEST)
Background: The information on the difference in clinical characteristics between severe and non-severe cases is limited in some countries including Iran. The objective of this case series is to compare the clinical characteristics, radiologic features, and laboratory findings between COVID-19 severe cases who received the intensive care unit (ICU) care with non-severe cases who did not receive ICU care. Methods: In this retrospective cohort study, 186 laboratory-confirmed patients with COVID-19 diagnosed from 1 March 2020 to 30 March 2020 were investigated. Results: This study population included 186 hospitalized patients with confirmed COVID-19. The median age was 47 years, and 88 (47.31%) were female. Of these patients, 48 were admitted and transferred to ICU. Of 186 patients, 44.62% had medical comorbidities including hypertension and diabetes. The most common clinical manifestation were shortness of breath 86.56%, myalgia 74.19%, and headache. Higher neutrophil counts, CRP, and LDH as well as the lower levels of lymphocytes were the most important laboratory finding among COVID-19 patients. As of April 15, 2020, 33 were still hospitalized. A total of 116 patients (62.70 %) had been discharged, and 36 patients (19.94 %) had died. Of the 48 patients admitted to the ICU, 33.33% have died. Conclusion: In the present study, shortness of breath was the most common clinical symptom, and the mortality rate in patients admitted to the ICU was about 33%, indicating that about one-third of patients with severe illness who admitted to the ICU section died.
REVIEW | doi:10.20944/preprints202004.0495.v1
Subject: Keywords: COVID - 19; coronavirus; respiratory syndrome; SARS-CoV; preventive and control measures
Online: 28 April 2020 (10:04:07 CEST)
The most striking and dramatic catastrophe, as on April 2020, is - COVID - 19. Understanding of the COVID-19, the causing agent- the virus and the resultant causalities are still evolving. Till now, there is no specific treatment, no vaccine for the COVID-19. At this stage, what is utmost important now to face the disaster is to put emphasis on the preparedness and responses: research to discover vaccine, antivirals as soon as possible. Till then, it is necessary to put emphasis on infection preventive and control measures like to avoid close contact of infected people showing symptoms of respiratory diseases, hand hygiene and coughing etiquette. To make the infection preventive and control measures a success, the followings are to make success: ‘quarantine’ ‘isolation’, ‘travel bans’, ‘cordon sanitaire’ and ‘social distancing’ measures. The tools of modern information technology could help the authority to manage and monitor the preventive measures. Above all, preventive and control measures will not be successful if we fail to make aware the common people about the fatality of the COVID - 19. So, rapid preparedness and responses to COVID-19 are critically essential to face such disaster. Not a single moment is to waste!
ARTICLE | doi:10.20944/preprints201908.0069.v1
Subject: Medicine & Pharmacology, Other Keywords: coenzyme Q deficiency; mitochondrial disease; respiratory chain; fatty acids; myopathy; ADCK2
Online: 6 August 2019 (07:52:35 CEST)
Fatty acids and glucose are the main bioenergetic substrates in mammals that are alternatively used during the transition between fasting and feeding. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle. In order to better understand the etiology of this rare disorder, we generated a heterozygous Adck2 knockout mouse model to perform in vivo and cellular studies using integrated analysis of physiological and omics data (transcriptomics-metabolomics). The data show that Aldh2+/- mice exhibits impaired fatty acid oxidation, liver dysfunction, and mitochondrial myopathy in skeletal muscle resulting in lower physical performance. Significant decrease in CoQ biosynthesis was observed and supplementation with CoQ partially rescued the phenotype both in the human subject and mouse model. These results indicate that ADCK2 is involved in organismal fatty acid metabolism and in CoQ biosynthesis in skeletal muscle. We propose that patients with isolated myopathies and myopathies involving lipid accumulation be tested for possible ADCK2 defect as they are likely to be responsive to CoQ supplementation.
ARTICLE | doi:10.20944/preprints201907.0155.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: immune system; immunedeficiency; respiratory tract infections; children; impedance; serum; laboratory diagnostics
Online: 11 July 2019 (09:12:55 CEST)
Despite considerable progress in the diagnosis of various diseases, an ideal, simple tool for diagnosing patients with respiratory tract infections has not yet been invented. Many simple diagnostic tests are widely available to most doctors, provided they are aware of the prevalence of primary immunodeficiency. Other, more accurate studies are available only to immunologists. The aim of the study was to investigate the occurrence of dependence between selected physical parameters of serum such as: electrical conductivity, electrical permeability, dielectric loss factor, and selected parameters of the immune system. In addition, we have also included the ionogram (Na, K, Cl, Ca, Mg) and glucose concentration. As a result of research, the statistically significant, but very weak correlations between impedance magnitude |Z| and platelet counts (PLT), mean platelet volume (MPV) and chloride ions (Cl-) were found. The statistically significant differences according |Z| between children with and without deficiency in parameters of the immune system were noticed. Values of |Z| are higher in the case of children without deficiency in parameters of the immune system. The method of impedance measurements presented in our work is significantly easier then biosensors presented by other scientists. Taking into account our results, it can be stated that this method is promising for fast and easy detection of immunological disorders.
ARTICLE | doi:10.20944/preprints201711.0175.v1
Subject: Earth Sciences, Environmental Sciences Keywords: carbon monoxide; COHb; air pollution; GIS interpolation; spatial analysis; respiratory diseases
Online: 27 November 2017 (09:13:06 CET)
This paper aims to investigate carbon monoxide (CO) concentrations on roadways of Karachi, potential blood levels carboxy-hemoglobin (COHb) in Karachi. Geographical information system (GIS) was used for spatial analysis of diseases potentiality while an interpolation technique has been applied for surface generation with town boundaries and later evaluates risk areas.The higher concentration of carbon monoxide in the ambient is mainly due to automobile emissions. The City center and CBD areas are more perilous.
BRIEF REPORT | doi:10.20944/preprints202008.0519.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2, COVID-19, Acute Respiratory Distress Syndrome, ARDS, Famotidine, Celecoxib
Online: 24 August 2020 (09:46:15 CEST)
Celecoxib as adjuvant therapy has been shown in a small randomized trial for Covid-19 to prevent clinical deterioration and rapidly improve thoracic computerized axial tomography (CT-chest)1. Multiple descriptive trials of high dose famotidine (both inpatient and outpatient) have demonstrated clinical response2,3,4. We describe the rapid clinical responses after increasing the celecoxib dosage to 400mg bid with high dose famotidine 80mg qid in both a critical inpatient who on baseline required 40 liters per minute high flow nasal insufflation and an outpatient who declined admission but had critical Covid-19 biomarkers.
HYPOTHESIS | doi:10.20944/preprints202007.0015.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: coronavirus; Substance P/Neurokinin-1 Receptor; respiratory illness; Infectious disease; trigeminal ganglion
Online: 3 July 2020 (05:54:18 CEST)
Novel severe acute respiratory syndrome coronavirus 2 infection (SARS-Cov-2) is an acute respiratory and infectious disease. This perspective aims to provide the basic understanding of the inflammation caused by SARS-Cov-2 and relation to trigeminal ganglion (TG). Virus enters through the mucous membranes of orofacial region and reach the TG where it resides and take control of its peptides including Substance P (SP).SP is the main neuropeptide, neuromodulator and neuro-hormone of TG, associated with nociception and inflammation under noxious stimulus. SP release is triggered and consequently, it affects the immune cells, blood vessels to release the mediators for inflammation. Cytokine storming is initiated and cause respiratory distress, bronchoconstriction and death in complicated cases. Neurokinin-1 Receptor (NK-1R) antagonist and glucocorticoids may be used to alleviate the symptoms and treat this infection. SP is the main culprit seem to be involved in the triggering of inflammatory pathways in SARS-Cov-2 infection. It has direct association with cardiorespiratory rhythm, sleep-wake cycle, nociception, ventilator responses and regulates many important physiological and pathological roles. Its over-secretion should be blocked by NK-1R antagonist. However, experimental work leading to clinical trials are mandatory for further confirmation.
REVIEW | doi:10.20944/preprints202005.0477.v1
Subject: Keywords: respiratory syncytial virus vaccine; clinical trial; safety and immunogenicity; RSV promising vaccine
Online: 31 May 2020 (16:07:57 CEST)
Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccines in pipeline to prevent it but a systematic review on immunogenicity and safety of vaccine is lacking. Methods: This systematic review of RSV vaccine clinical trials was undertaken using 4 databases. Searches were conducted using both controlled vocabulary terms such as ‘Respiratory Syncytial Virus, Human’, ‘Respiratory Syncytial Virus Infections’, ‘Respiratory Syncytial Virus Vaccines’, ‘Immunization’, ‘Immunization Programs’ and ‘Vaccines’ and corresponding text word terms. The searches for published papers were limited to clinical trials published from January 2000 to August 6th, 2018. RSV infection case was defined as RSV associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically-confirmed test (Western Blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case. Results: Of 4395 publications, 24 were included and data were extracted covering 4 major types of RSV vaccine candidates, these being live-attenuated/chimeric (n=9), recombinant-vector (n=10), subunit (n=1) and nanoparticle vaccines (n=4). For RSV infection cases, 7 trials were involved and none of them showed a vaccine-related increased MAARI during RSV surveillance season. Conclusion: LID ∆M2-2, MEDI M2-2, and RSVcps2 (live-attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate was considered as a potential effective vaccine. Although no promising vaccine was identified from pregnant-women test, RSV F-024 subunit vaccine candidate and an RSV F nanoparticle vaccine showed encouraging results in healthy non-pregnant women.
REVIEW | doi:10.20944/preprints202003.0353.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: COVID-19; SARS-CoV-2; Severe Acute Respiratory Syndrome Coronavirus-2; Curcumin
Online: 24 March 2020 (03:16:22 CET)
COVID-19 (coronavirus disease 2019) is a public health emergency of international concern caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). As of this time, there is no known effective pharmaceutical, phytopharmaceutical or traditional medicine for cure or prevention of COVID-19, although it is urgently needed. In this review, based on the current understanding of the disease molecular mechanisms of novel Coronavirus SARS-CoV-2 and its closest relative SARS-CoV and other human Coronaviruses, I have identified some naturally occurring plant based substances and Ayurvedic medicinal herbs that could feasibly be tested as a matter of urgency for prevention as well as therapeutic option for COVID-19 in India and other parts of the world. I conclude that dried rhizome of Curcuma longa L. i.e. turmeric, and its active ingredient curcumin may be effective in preventing as well as cure the COVID-19 pandemic due to its proven antiviral activities, this however need to be tested by appropriate clinical trials as research priority.
ARTICLE | doi:10.20944/preprints201908.0252.v1
Subject: Materials Science, Biomaterials Keywords: Chinese fir wood; sodium silicate; phenol formaldehyde oligomer; respiratory impregnation; comparative study
Online: 25 August 2019 (15:32:30 CEST)
To compare The effects of organic and inorganic impregnation on the properties of unmodified, phenol formaldehyde oligomer-modified (PFOMCF), and sodium silicate-modified Chinese fir wood (SSMCF) were compared using samples prepared using the respiratory impregnation method. Impregnation and reinforcement effects and water resistance of PFOMCF and SSMCF were compared and the results was showed that the weight percentage gain, density increase rate, bending strength, and compressive strength of SSMCF were clearly higher than those of PFOMCF and had a lower water absorption rate within 60 h. The impregnation and reinforcement effects and dimensional stability of SSMCF were better than those of PFOMCF. FT-IR, XRD, CONE, and TGA examinations were used to test and analyze the chemical structure, crystalline structure, flame retardancy, and heat resistance of these modified woods. The results indicated that SSMCF possessed more hydrogen bonds than PFOMCF and that Si–O–Si chemical bonding with high bond energy was formed. Meanwhile, the weakened degree of the diffraction peak of SSMCF was much less than that of PFOMCF. These results explained that the mechanical properties and water resistance of SSMCF were better than PFOMCF. Compared with PFOMCF, SSMCF had a lower heat release rate (HRR), peak-HRR, mean-HRR, total heat release, smoke production rate, and total smoke production as well as higher thermal decomposition temperature and residual rate. Inorganic sodium silicate was shown to be a better flame retardant, while SSMCF had good smoke suppression effects, thermal stability, and safety performance in the case of fire.
ARTICLE | doi:10.20944/preprints201808.0136.v2
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: acute toxicity; cardiovascular depression; intravenous lipid emulsion; propofol; rat model; respiratory depression
Online: 23 October 2018 (09:34:43 CEST)
Abstract: Background and objective: Propofol is an anesthetic agent that is frequently used in anesthesia induction, maintenance and sedation. Propofol has severe side effects such as hypotension, bradycardia and respiratory depression. Although propofol is commonly used, there is no known antidote for its toxic effects. An approach to prevent toxic effects of propofol would be beneficial. The aim of this study was to assess the effects of intravenous lipid emulsion (ILE) therapy in the prevention of depressive effects of propofol on cardiovascular and respiratory systems. Materials and methods: Twenty-eight Sprague-Dawley adult rats were randomly divided into 4 groups. The saline-administered group was determined as the Control group. The second group was administered propofol (PP group); the third group was administered ILE (ILE group), and the fourth was administered propofol with ILE therapy (ILE+PP group). Systolic blood pressure (SBP), Diastolic blood pressure (DBP), Mean arterial blood pressure (MAP), Respiratory rate (RR), Heart rate (HR) and mortality were recorded at 10 points during 60 minutes. A repeated measures linear mixed-effect model with unstructured covariance was used to compare the groups. Results: In the PP group, SBP, DBP, MAP, RR and HR levels were declining steadily; all rats in this group died after 60 minutes. In the ILE+PP group, after a while, the decreased SBP, DBP, MAP, RR and HR levels increased SBP, DBP, MAP, RR and HR levels of the Propofol group were found to be significantly lower than those of the other groups (p<0.01). The mortality rate was 100% (surviving period, 60 min) for the PP group, whereas 0% for the ILE, ILE+PP and Control groups. Conclusion: Our results suggest that undesirable side effects that can be seen after propofol application such as hypotension, bradycardia and respiratory depression might be prevented by using ILE therapy.
ARTICLE | doi:10.20944/preprints201809.0534.v1
Subject: Social Sciences, Geography Keywords: syndemic; El Niño; infectious disease; diarrhea; malaria; respiratory; cholera; spatial cluster; GIS
Online: 27 September 2018 (06:04:08 CEST)
El Niño is a quasi-periodic pattern of climate variability and extremes often associated with hazards and disease. While El Niño links to individual diseases have been examined, less is known about the cluster of multi-disease risk referred to as an ecosyndemic, which emerges during extreme events. The objective of this study was to explore a mapping approach to represent the spatial distribution of ecosyndemics in Piura, Peru at the district-level during the first few months of 1998. Using geographic information systems and multivariate analysis, two methodologies were employed to map disease overlap of 7 climate-sensitive diseases and construct an ecosyndemic index, which was then mapped and applied to another El Niño period as proof of concept. The main findings showed that many districts across Piura faced multi-disease risk over several weeks in the austral summer of 1998. The distribution of ecosyndemics were spatially clustered in western Piura among 11 districts. Furthermore, the ecosydemic index in 1998 when compared to 1983 showed a strong positive correlation, demonstrating the utility of the index. The study supports PAHO efforts to develop multi-disease based and interprogrammatic approaches to control and prevention, particularly for climate and poverty-related infections in Latin America and the Caribbean.
ARTICLE | doi:10.20944/preprints201710.0168.v1
Subject: Life Sciences, Virology Keywords: Middle East respiratory syndrome; MERS; coronavirus; comorbidity; infection; camel; zoonosis; emerging virus
Online: 27 October 2017 (05:45:00 CEST)
The human coronaviruses (CoV) include HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1, some known for decades. The severe acute respiratory syndrome (SARS) CoV briefly emerged into the human population but was controlled. In 2012 another novel severely human pathogenic CoV – Middle Eastern Respiratory Syndrome (MERS)-CoV was identified in the Kingdom of Saudi Arabia, where 80% of over 2,000 human cases have been recorded across five years. Targeted research remains key to developing control strategies for MERS-CoV, a cause of mild illness in its camel reservoir. A new therapeutic toolbox being developed in response to MERS is also teaching us more about how CoVs cause disease. Travel-related cases continue to challenge the world’s surveillance and response capabilities and more data are needed to understand unexplained primary transmission. Signs of genetic change have been recorded but it remains unclear whether any impact on clinical disease. How camels came to carry the virus remains academic to the control of MERS. To date, human-to-human transmission has been inefficient, but virus surveillance, characterisation and reporting are key to responding to any future change. MERS-CoV is not currently a pandemic threat; it is spread mainly with the aid of human habit and error.
REVIEW | doi:10.20944/preprints201611.0099.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: pneumonia; acute respiratory distress syndrome; pathogenesis; protein-homeostasis-system; corticosteroid; intravenous immunoglobulin
Online: 18 November 2016 (10:18:58 CET)
Acute respiratory distress syndrome (ARDS) is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved in the immunopathogenesis of ARDS. There may be etiologic substances that have an affinity for respiratory cells and induce lung cell injury in cases of ARDS. These substances originate not only from pathogens, but also from injured host cells. At the molecular level, these substances have various sizes and biochemical characteristics, classifying them as protein substances and non-protein substances. Immune cells and immune proteins may recognize and act on these substances, including pathogenic proteins and peptides, depending upon the size and biochemical properties of the substances (this theory is known as the protein-homeostasis-system hypothesis). The severity or chronicity of ARDS depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, or the repertoire of specific immune cells that control the substances. Therefore, treatment with early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) as soon as possible may reduce aberrant immune responses in the potential stage of ARDS.
REVIEW | doi:10.20944/preprints202003.0235.v2
Subject: Medicine & Pharmacology, Nutrition Keywords: acute respiratory distress syndrome (ARDS); ascorbic acid; cathelicidin; coronavirus; COVID-19; cytokine storm; influenza; observational; pneumonia, prevention; respiratory tract infection; solar radiation; treatment; UVB; vitamin C; vitamin D
Online: 30 March 2020 (05:48:43 CEST)
The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
ARTICLE | doi:10.20944/preprints202203.0227.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; FDG-PET/CT; respiratory function test; complications; inflammatory; SARS-CoV-2
Online: 16 March 2022 (09:26:16 CET)
Evaluation of the usefulness of [18F]FDG-PET/CT in the short-term follow-up of patients admitted for COVID-19 pneumonia and to explore the association of findings with clinical prognostic markers. Prospective study included 20 patients admitted to hospital with COVID-19 pneumonia between November 2020 and March 2021. Clinical and laboratory test findings were gathered at admission, 48-72h post-admission, and 2-3 months post-discharge. [18F]FDG-PET/CT and respiratory function tests were performed at 2-3 months post-discharge. Lung volumes (TLC), spirometry (FVC, FEV1), lung diffusion capacity for carbon monoxide (DLCO), and respiratory muscle strength were measured. PET/CT images were qualitatively and semi-quantitatively interpreted. Volumetric [18F]FDG-PET/CT results were correlated with laboratory test and respiratory parameters. Eleven [18F]FDG-PET/CT (55%) were positive. The main finding was hypermetabolic lymphade-nopathy in the mediastinum (90.9%). SUVpeak of the target mediastinum lesion was correlated with neutrophil and lymphocyte counts. Eleven (55%) patients had impaired respiratory function, most frequently a reduced DLCO (35%). SUVpeak was positively correlated with %predict-ed-DLCO values. Pulmonary TLG was negatively correlated with %predicted-DLCO and TLC values. In the short-term follow-up of patients hospitalized for COVID-19 pneumonia, [18F]FDG-PET/CT findings revealed significant detectable inflammation in lungs and mediastinal lymph nodes that correlated with pulmonary function impairment in more than half of the patients.
ARTICLE | doi:10.20944/preprints202106.0613.v1
Subject: Mathematics & Computer Science, Algebra & Number Theory Keywords: LRTI; URTI; Asthma; Cough Classification; Respiratory Pathology Classification; MFCCs; BiLSTM; Deep Neural Networks
Online: 25 June 2021 (09:45:00 CEST)
Intelligent systems are transforming the world, as well as our healthcare system. We propose a deep learning-based cough sound classification model that can distinguish between children with healthy versus pathological coughs such as asthma, upper respiratory tract infection (URTI), and lower respiratory tract infection (LRTI). In order to train a deep neural network model, we collected a new dataset of cough sounds, labelled with clinician's diagnosis. The chosen model is a bidirectional long-short term memory network (BiLSTM) based on Mel Frequency Cepstral Coefficients (MFCCs) features. The resulting trained model when trained for classifying two classes of coughs -- healthy or pathology (in general or belonging to a specific respiratory pathology), reaches accuracy exceeding 84\% when classifying cough to the label provided by the physicians' diagnosis. In order to classify subject's respiratory pathology condition, results of multiple cough epochs per subject were combined. The resulting prediction accuracy exceeds 91\% for all three respiratory pathologies. However, when the model is trained to classify and discriminate among the four classes of coughs, overall accuracy dropped: one class of pathological coughs are often misclassified as other. However, if one consider the healthy cough classified as healthy and pathological cough classified to have some kind of pathologies, then the overall accuracy of four class model is above 84\%. A longitudinal study of MFCC feature space when comparing pathologicial and recovered coughs collected from the same subjects revealed the fact that pathological cough irrespective of the underlying conditions occupy the same feature space making it harder to differentiate only using MFCC features.
ARTICLE | doi:10.20944/preprints202105.0462.v1
Subject: Engineering, Automotive Engineering Keywords: Respiration topography; waterpipe; hookah; combustible cigarettes, wearable respiratory monitor; lung volume; inhalation topography
Online: 20 May 2021 (09:30:48 CEST)
Background: Limited research has been done to measure ambulatory respiratory behavior, in particular those associated with tobacco use, in the natural environment due to a lack of monitoring techniques. Respiratory topography parameters provide useful information for modelling particle deposition in the lung and assessing exposure risk and health effects associated with tobacco use. Commercially available Wearable Respiratory Monitors (WRM), such as the Hexoskin Smart Garment, have embedded sensors which measure chest motion and may be adapted for measuring ambulatory lung volume. Methods: Self-reported ‘everyday’ and ‘some days’ Hookah and Cigarette smokers were recruited for a 3-day natural environment observation study. Participants wore the Hexoskin shirt while using their preferred tobacco product. The shirt was calibrated on them prior to, during, and after the observation period. A novel method for calculating the calibration parameters is presented. Results: N=5 Hookah and N=3 Cigarette participants were enrolled. Calibration parameters were obtained and applied to the observed chest motion waveform from each participant to obtain their lung volume waveform. Respiratory topography parameters were derived from the lung volume waveform. Conclusion: The feasibility of using the Hexoskin for measuring ambulatory respiratory topography parameters in the natural environment is demonstrated..
REVIEW | doi:10.20944/preprints202007.0613.v3
Subject: Biology, Other Keywords: infective dose; SARS-CoV-2; COVID-19; respiratory viruses; viral load; viral dynamics
Online: 7 December 2020 (11:36:05 CET)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. Prevention and control strategies require an improved understanding of SARS-CoV-2 dynamics. We did a rapid review of the literature on SARS-CoV-2 viral dynamics with a focus on infective dose. We sought comparisons of SARS-CoV-2 with other respiratory viruses including SARS-CoV-1 and MERS-CoV. We examined laboratory animal, and human studies. The literature on infective dose, transmission, and routes of exposure was limited specially in humans, and varying endpoints were used for measurement of infection. We propose the minimum infective dose of COVID-19 in humans, is higher than 100 particles, possibly slightly lower than the 700 particles estimated for H1N1 influenza. Despite variability in animal studies, there was some evidence that increased dose at exposure correlated with higher viral load clinically, and severer symptoms. Higher viral load measures did not reflect COVID-19 severity. Aerosol transmission seemed to raise the risk of more severe respiratory complications in animals. An accurate quantitative estimate of the infective dose of SARS-CoV-2 in humans is not currently feasible and needs further research. Further work is also required on the relationship between routes of transmission, infective dose, co-infection, and outcomes.
REVIEW | doi:10.20944/preprints202012.0097.v1
Subject: Life Sciences, Molecular Biology Keywords: acute respiratory distress syndrome; mesenchymal stem/stromal cells,; exosome; COVID-19; Clinical trials
Online: 4 December 2020 (10:10:11 CET)
Coronavirus disease 2019 (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached a global epidemic across the world after first reported in Wuhan, China’s Hubei province in December 2019. The pandemic is also associated with acute respiratory distress syndrome (ARDS) characterized by excess inflammation, progressive arterial hypoxemia and dyspnea. Mesenchymal stem/ stromal cells (MSCs) have been investigated as treatment for ARDS due to immunomodulatory property. Exosomes derived from MSCs play an important role in paracrine signaling of MSCs, thereby contributed to immunomodulation of the immune microenvironment. Exosomes are emerged as potential alternative to MSC cell therapy with superiority of safety. In this review, we will introduce MSC-derived exosomes and briefly discuss current progress on MSCs and exosomes in ARDS, which may have clinical implications in pathogenesis and treatment of COVID-19.
REVIEW | doi:10.20944/preprints202007.0349.v1
Subject: Life Sciences, Molecular Biology Keywords: systematic review; extracellular vesicles; EVs; asthma; therapy; inflammation; respiratory disease; airway hyperresponsiveness; BALF
Online: 16 July 2020 (12:52:03 CEST)
Asthma is the most common chronic disease in children. It is characterized by difficulty in breathing and chronic airway inflammation associated with narrowing of the airways, and airway hyperresponsiveness. If left untreated, asthma can lead to respiratory distress and even death. A number of medications are available and prescribed to manage asthma. Yet despite that, only half of the asthmatic patients are able to control their condition. Extracellular vesicles (EVs) play an important role in transporting contents such as nucleic acids, proteins, and lipids to other cells. While EVs have been extensively studied as biomarkers of various pathological states, evidence indicates that they can play protective and therapeutic roles in mitigating diseases such as cancer, cardiovascular disease and asthma. Here we propose to conduct a systematic review that provides a detailed analysis of the therapeutic effect of EVs in mitigating the primary (inflammation, airway hyperresponsiveness) and secondary outcomes (airway remodelling, molecular indices of cellular signalling, and inflammatory mediators in serum) associated with asthma in preclinical studies.
REVIEW | doi:10.20944/preprints202006.0216.v2
Subject: Life Sciences, Virology Keywords: SARS-coronavirus; Severe Acute Respiratory Syndrome; COVID-19; Stool; Urine; Wastewater; Wastewater-based epidemiology
Online: 18 June 2020 (09:29:00 CEST)
The COVID-19 pandemic has revealed many knowledge gaps with implications toward the speed and nature of our response to contain, assess and mitigate risk. The routine discharge of treated and untreated wastewater into rivers and coastal waters has placed SARS-CoV-2 viability in wastewater at the centre of an emerging hazard and potential risk to water industry workers and the public who come into contact with sewage-impacted water. Here we provide a review of the Severe Acute Respiratory Syndrome coronavirus primary literature that presents the evidence base pertaining to the key questions of whether the SARS-CoV-1 and SARS-CoV-2 is shed in stool and urine, is recoverable, and infectious in wastewater. We discuss the challenges posed by the current literature base and the extent to which the current evidence is fit for the purpose of informing robust human and environmental risk assessments.
Subject: Keywords: COVID-19; SARS-CoV-2; coronavirus; severe acute respiratory syndrome coronavirus; meta-analysis
Online: 16 March 2020 (01:06:04 CET)
Introduction: The 2019 novel coronavirus (COVID-19) is very contagious, and can be transmitted to other people by droplet, aerosol, sneezing, infected surface, and cough. There is no vaccine or effective treatment at this time. Therefore, the prevention of COVID-19 and the rapid diagnosis of infected patients is crucial. Method: We searched all relevant literature published up to February 28, 2020, from Embase, Scopus, PubMed, Web of Science, and the Cochrane library to collect the studies that reported clinical and laboratory characteristics of COVID-19 infected patients. The study quality was assessed with the Critical Appraisal Checklist. Depending on the heterogeneity test, we used either random or fixed-effect models to analyze the appropriateness of the pooled results. Result: Twenty studies were included in the meta-analysis, including a total of 52,251 patients with confirmed COVID-19 infection. 69.5% (95% CI 54.5-81, p < 0.001) of patients had a history of recent travel to Wuhan, contact with people from Wuhan, or lived in Wuhan. The most common symptoms among COVID-19 infected patients were fever 85.6 % (95% CI 73 -93, p < 0.001), and cough 63 % (95% CI 55.5-70, p < 0.001), respectively. The laboratory analysis showed that thrombocytosis was present in 91% (95% CI 81-98, p < 0.001) CRP was elevated in 81% (95% CI 65-91, p < 0.001), and lymphopenia in 62.5% of cases (95% CI 42-79, p < 0.001). The most common radiographic signs were bilateral involvement in 76.8% (95% CI 62.5-87, p < 0.001) and consolidation in 75.5% (95% CI 50.5-91, p < 0.001) of patients. Most patients (85.4%) were hospitalized, 20.6% of patients were admitted to the ICU in critical condition, and the mortality rate was 5.6%. Conclusions: Fever and cough are the most common symptoms of COVID-19 infection in the literature published to date. Thombocytosis, lymphopenia, and increased CRP were common lab findings although most patients included in the overall analysis did not have laboratory values reported. The most common radiographic sign was bilateral involvement in and consolidation. Among Chinese patients with COVID-19, rates of hospitalization, critical condition, and hospitalization were high in this study, but these findings may be biased by reporting only confirmed cases.
ARTICLE | doi:10.20944/preprints201907.0250.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: socioeconomic status; indoor air pollution; acute respiratory infection; cooking fuel; under-five children
Online: 23 July 2019 (07:45:08 CEST)
Background: Low-income families often depend on fuels such as wood, coal, and animal dung for cooking. Such solid fuels are highly polluting and are a primary source of indoor air pollutants (IAP). We examined the association between solid fuel use (SFU) and acute respiratory infection (ARI) among under-five children in Afghanistan and the extent to which this association varies by socioeconomic status (SES) and gender. Materials and Methods: This is a cross-sectional study based on de-identified data from Afghanistan’s first standard Demographic and Health Survey conducted in 2015. The sample consists of ever-married mothers with under-five children in the household (n=27,565). We used mixed-effect Poisson regression models with robust error variance accounting for clustering to examine the associations between SFU and ARI among under-five children after adjusting for potential confounders. We also investigated potential effect modification by SES and sex. Additional analyses were conducted using an augmented measure of the exposure to IAP accounting for both SFU and the location of cooking/kitchen (High Exposure, Moderate, and No Exposure). Results: Around 70% of households reported SFU, whereas the prevalence of ARI was 17.6%. The prevalence of ARI was higher in children living in households with SFU compared to children living in households with no SFU (adjusted prevalence ratio [aPR]= 1.10; 95%CI: 0.98, 1.23). We did not observe any effect modification by SES or child sex. When using the augmented measure of exposure incorporating the kitchen’s location, children highly exposed to IAP had a higher prevalence of ARI compared to unexposed children (aPR 1.17; 95% CI: 1.03, 1.32). SES modified this association with the strongest associations observed among children from the middle wealth quintile. Conclusion: The findings have significant policy implications and suggest that ARI risk in children may be reduced by ensuring clean cookstove as well as clean fuels and acting on the socio-environmental pathways.
REVIEW | doi:10.20944/preprints202208.0498.v1
Subject: Life Sciences, Immunology Keywords: Secretory IgA; IgA class switching; SARS-CoV-2; respiratory pathogens; nasal vaccines; vaccine adjuvants
Online: 30 August 2022 (02:33:19 CEST)
Nasal cavity is a primary checkpoint for the invasion of several respiratory pathogens. Numerous pathogens including SARS-CoV-2, S. pneumonia, S. aureus, etc., adhere to the nasal epithelium or mucus to invade and trigger an infection. IgA serves as the first line of defense against foreign antigens and pathogens. They exhibit cross-reactivity against a diverse variety of antigens through immune exclusion, which intercepts the invasion of pathogens through the mucosal lining. Advances in intranasal immunization technology underscore the elevated neutralizing IgA levels at local and distal mucosa in contrast to the parenteral vaccines. This review highlights the adjuvants that induce IgA class switching and the challenges of maintaining nominal IgA levels at the mucosal surface. Finally, the review features the paradigm-shifting of conventional immunization techniques to IgA-inducing vaccines to enhance protection against homologous and heterologous pathogens.
CASE REPORT | doi:10.20944/preprints202204.0285.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: GLDN variant; gliomedin; juvenile progressive respiratory insufficiency; diaphragmatic hypomotility; scoliosis; arthrogryposis; LCCS11; axonopathy; FADS
Online: 29 April 2022 (03:36:40 CEST)
Lethal congenital contracture syndrome 11 (LCCS11) is a form of arthrogryposis multiplex congenita (AMC) which is associated with mutations in the gliomedin gene (GLDN) and has been known to be severely life-shortening, mainly due to respiratory insufficiency. Patients with this condition have been predominantly treated by pediatricians as they usually do not survive beyond childhood. In this case report we present a young adult who developed severe progressive respiratory insufficiency as a teenager due to diaphragmatic hypomotility and was diagnosed with LCCS11 following the finding of compound heterozygous pathogenic variants in GLDN. This case demonstrates the importance of screening for neuromuscular diseases in well-child visits and follow-ups of patients at risk for gross and fine motor function developmental delay. It also underscores the significance of including LCCS11 and other axonopathies in the differential diagnosis of juvenile onset of respiratory insufficiency, highlights that patients with this condition may present to adult practitioners and questions whether the nomenclature of this condition with various phenotypes should be reconsidered due to the stigmatizing term ‘lethal’.
ARTICLE | doi:10.20944/preprints202105.0731.v1
Subject: Life Sciences, Biochemistry Keywords: cytokine storm; COVID-19; CD169; inflammation; respiratory outcome; T-cell exhaustion; COVID-19 therapy
Online: 31 May 2021 (10:28:24 CEST)
Background: CD169 has been found overexpressed in the blood of COVID-19 patients and identified as a biomarker in the early disease. We have analysed CD169 in blood cells of COVID-19 patients to assess its role as predictive marker of the disease. Methods : The ratio of the CD169 Median median Fluorescence fluorescence Intensity intensity of CD169 between monocytes and lymphocytes (CD169 RMFI ) was analysed by flow cytometry in blood samples of COVID-19 patients (COV) and healthy donors (HD ) and correlated with immunophenotyping, inflammatory markers, cytokines mRNA expression, pulmonary involvement and disease progression. Results: CD169 RMFI increased in COV but not in HD. CD169 RMFI correlated with T-cell differentiation and exhaustion markers as well as with B cells maturation and differentiation. In vitro stimulation of PBMCs of HD with SARS-CoV-2 Spike spike protein induced CD169 RMFI together with IL-6 and IL-10 gene expression. Likewise, CD169 RMFI correlated with blood cytokine mRNA levels, inflammatory markers, and pneumonia severity in patients which that had not received any treatment at sampling. Notably, in untreated patients, CD169 RMFI reflected the respiratory outcome during hospitalization. Conclusion : Considering the immunological role of CD169 and its involvement during the infection and the progression of COVID-19, it could be considered as an early biomarker to evaluate disease progression and clinical outcome.
REVIEW | doi:10.20944/preprints202103.0034.v1
Subject: Life Sciences, Biochemistry Keywords: respiratory illness; pathogenicity; virulence; natural selection; colds; influenza; rhinovirus; weather; climate; Tropics; summer; winter
Online: 1 March 2021 (17:14:19 CET)
This review seeks to explain four features of viral respiratory illnesses that have perplexed generations of virologists: (1) the seasonal timing of respiratory illness; (2) the common viruses causing respiratory illness worldwide, including year-round disease in the Tropics; (3) the rapid response of outbreaks to weather, specifically temperature; (4) the rapid arrival and termination of epidemics caused by influenza and other viruses. The inadequacy of the popular explanations of seasonality is discussed, and a simple hypothesis is proposed, called Temperature Dependent Viral Tropism (TDVT), that is compatible with the above features of respiratory illness. TDVT notes that viruses can transmit themselves more effectively if they moderate their pathogenicity (thereby maintaining host mobility) and suggests that endemic respiratory viruses accomplish this by developing thermal sensitivity within a range that supports organ-specific viral tropism within the human body, whereby they replicate most rapidly at temperatures below body temperature. This allows them to confine themselves to the upper respiratory tract and to avoid infecting the lungs, heart, gut etc. Biochemical and tissue-culture studies show that “wild” respiratory viruses show such natural thermal sensitivity. The typical early autumn surge of colds and the existence of respiratory illness in the Tropics year-round at intermediate levels are explained by the tendency for strains to adapt their thermal sensitivity to their local climate and season. The TDVT hypothesis has important practical implications for preventing and treating respiratory illness including Covid-19. TVDT is testable with many options for experiments to increase our understanding of viral seasonality and pathogenicity.
HYPOTHESIS | doi:10.20944/preprints202101.0389.v1
Subject: Medicine & Pharmacology, Allergology Keywords: respiratory illness; pathogenicity; virulence; natural selection; colds; influenza; rhinovirus; weather; climate; Tropics; summer; winter
Online: 19 January 2021 (16:42:56 CET)
This review seeks to explain four features of viral respiratory illnesses that have perplexed many generations of microbiologists: (1) the seasonal occurrence of viral respiratory illness; (2) the occurrence of respiratory illness year-round in the Tropics; (3) the rapid response of illness to temperature drops in temperate regions; (4) the explosive arrival and rapid termination of epidemics caused by influenza and other respiratory viruses. I discuss the inadequacy of the popular explanations of seasonality, and propose a simple hypothesis, called Temperature Dependent Viral Tropism (TD-VT), that is compatible with the above and other features of respiratory illness. TD-VT notes that viruses can often transmit themselves more effectively if they moderate their pathogenicity (thereby maintaining the mobility of their hosts) and suggests that most endemic respiratory viruses accomplish this by developing thermal sensitivity, in the sense that they normally replicate rapidly only at temperatures below normal body temperature. This allows them to confine themselves to the upper respiratory tract and to avoid infecting the lungs, heart, gut etc. I review biochemical and tissue-culture studies that found that “wild” respiratory viruses often show natural thermal sensitivity within a range that supports organ-specific tropism within the human body, and I discuss the evident tendency for viral strains to adapt their thermal sensitivity to their local climate and season. I also explore the possible misinterpretation of early experiments where volunteers were inoculated nasally with viral samples and then chilled. Next, I discuss the practical implications of the TD-VT hypothesis for preventing and treating respiratory illness. Finally, I note that the hypothesis is very testable and make suggestions for the most important experiments to increase our understanding of the seasonality and pathogenicity of viral respiratory illness.
COMMUNICATION | doi:10.20944/preprints202004.0445.v2
Subject: Keywords: COVID-19; Coronavirus; Respiratory Distress; Tobacco Smoking; Correlation Statistics; Conditional Probability; Regression; China; U.S.A.
Online: 27 July 2020 (05:59:51 CEST)
The novel COVID-19 disease is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a new virus of the coronavirus family, SARS- CoV-2. Multiple studies have already reported that risk factors for severe disease include older age and the presence of at least one of several underlying health conditions. However, a recent physiopathological report and the French COVID-19 scientific council have postulated a protective effect of tobacco smoking. Thanks to a meta-analysis, we have been able to demonstrate the statistical significance in this regard of twelve series from China, France and in the US, reporting three different smoking status (current smoker,former smoker, with a smoking history) as well as disease severity (with respectively odds-ratio of 1.78 [1.08-3.10], 4.60 [3.13-7.17], 2.74 [0.63-5.89]). Subsequently and using a Bayesian approach we have established that past, and present smoking is associated with more severe COVID-19 outcomes. Finally, we refute claims linking general population smoking status (N=O(10^8) or O(10^9)) to much smaller disease course series (N=O(10^4)). The latter point in particular is presented to stimulate academic discussion, and must be further investigated by well-designed studies.
ARTICLE | doi:10.20944/preprints202004.0308.v5
Subject: Medicine & Pharmacology, Other Keywords: Covid-19; SARS-Cov-2; Mortality rate; Cancer; Cardiovascular disease; Respiratory disease; Diabetes; Kidney diseases; April; May
Online: 3 June 2020 (05:49:12 CEST)
Covid-19 has given a halt to all the activities in the world. Europe was most affected, followed by the United States of America. It has taken more than 350000 lives until now. In this study, we have assessed the severity of Covid-19 by analyzing the mortality rate of Covid-19 and other chronic diseases. The Covid-19 data and “death rate” data caused by other diseases were downloaded from the world health organization (WHO) website. A normalized method was used to see the mortality rate of Covid-19 in comparison to other diseases. The deaths caused by Covid-19 in April 2020 have overtaken the average number of deaths caused by Cancer, Cardiovascular diseases, and other diseases in Belgium, the United Kingdom (UK), Spain, France, and Ireland. Covid-19 was found to be strongly correlated with non-communicable respiratory diseases and Cancer with correlation coefficients 0.73 and 0.67 respectively. The severity of Covid-19 in the United States of America (USA) was moderate. The severity of Covid-19 in Asian countries was found to be low. Europe showed the highest diversity in the mortality rate of Covid-19. On average, except for a few European countries, Cardiovascular diseases, cancer, and non-communicable respiratory diseases were still more lethal and caused more deaths than Covid-19.
HYPOTHESIS | doi:10.20944/preprints202004.0349.v1
Subject: Keywords: Novel Coronavirus; respiratory distress; Favipiravir; statistics; correlation; beta thalassemia; immunisation; Italy; Sardinia; regression; heme
Online: 19 April 2020 (13:48:56 CEST)
The novel coronavirus pneumonia (COVID-19) is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a novel virus of the coronavirus family, SARSCoV-2. A recent pre-print study has showed a heme attack on the 1-beta chain of hemoglobin by COVID19. Beta-thalassemia results of a default in the hemoglobin beta- chain synthesis. 1,5% global population are heterozygotes for this disease. In this study, by a multiple linear regression, we have analyzed the evolution of COVID-19 infection in three Italian regions (Puglia, Sardinia, Sicilia) with different beta-thalassemic prevalences, in order to search a link. The results have showed that betathalassemic heterozygote population prevalence is correlated to immunity against COVID-19, by a regression. This paper is only for academic discussion, the hypotheses and conclusions needs to be confirmed by further research .
ARTICLE | doi:10.20944/preprints201909.0275.v1
Subject: Life Sciences, Other Keywords: ultrafine particles; aerosol; urban street canyon; outdoor pollution; indoor air quality; respiratory doses; mppd
Online: 24 September 2019 (12:25:44 CEST)
The amount of outdoor particles that indoor environments receive depends on the particle infiltration factors (Fin), peculiar of each environment, and on the outdoor aerosol concentrations and size distributions. The respiratory doses received, while residing indoor, will change accordingly. This study aims to ascertain to what extent such doses are affected by the vertical distance from the traffic sources. Particle number size distributions have been simultaneously measured at street level and at about 20 m height in a street canyon in downtown Rome. The same Fin have been adopted to estimate indoor aerosol concentrations, due to the infiltration of outdoor particles and then the relevant daily respiratory doses. Aerosol concentrations at ground floor were more than double than at 20 m height and richer in ultrafine particles. Thus, although aerosol infiltration efficiency was on average higher at 20 m height than at ground floor, particles more abundantly infiltrated at ground level. On a daily basis, this involved a 2.5-fold higher dose at ground level than at 20 m height. At both levels, such doses were greater than those estimated over the period of activity of some indoor aerosol sources, therefore they represent an important contribution to the total daily dose.
ARTICLE | doi:10.20944/preprints202202.0333.v1
Subject: Medicine & Pharmacology, Allergology Keywords: antibody; BNT162b2; coronavirus disease 2019; severe acute respiratory syndrome coronavirus 2; vaccine hesitancy; vaccine booster
Online: 25 February 2022 (10:01:23 CET)
This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive the third dose of coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. Accordingly, the study included participants who provided answer in the questionnaire whether they have an intent to receive the third dose of vaccine. Data on sex, age, area of residence, adverse reactions after the second vaccination, whether the third vaccination was desired, and reasons to accept or hesitate booster vaccination were retrieved. Among the 2439 participants with mean (±SD) age of 52.6±18.9 years, and median IgG-S antibody titer of 324.9 (AU/mL), 97.9% of participants indicated their intent to accept a third vaccination dose. The logistic regression revealed that younger age (OR=0.98; 95% CI: 0.96-1.00) and higher antibody level (OR=2.52; 95% CI: 1.27-4.99) are positively associated with the third vaccine hesitancy. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had significant impact on the third vaccination behavior. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken in these groups that are likely to hesitate the third vaccine, subsequently increasing booster contact rate.
ARTICLE | doi:10.20944/preprints202107.0015.v1
Subject: Keywords: characterization; life cycle assessment; life cycle impact assessment; normalization; particulate matter; respiratory inorganics; water vapor
Online: 1 July 2021 (11:16:42 CEST)
Life cycle assessment (LCA) is being included formally in EcoDesign regulations. Especially product carbon footprint will be mandatory in Europe. However, life cycle impact assessment including global warming potential (GWP) in LCA is hampered by several challenges. One of these is lack of water vapor characterization indexes for GWP. A life cycle inventory profile for air transport fuel including water vapor emissions is evaluated with state-of-the-art practice, i.e. EF Method and ILCD 2011 Midpoint+ and neglecting water vapors high altitude GWP compared to carbon dioxide. Then the characterization factor in GWP100 for water vapor and alternate normalization for particulates are introduced. The results are compared. The main findings are that the EF method and ILCD both generate rather realistic results for Particulate Matter and Respiratory Inorganics mid-point indicators, respectively, but the amount of premature deaths should be better allocated to different specific emissions, and that water vapor may dominate the GWP100 result over the usual carbon dioxide. LCIA mid-points need measurable and understandable bases. The common knowledge of water vapor’s GWP100 should not be neglected in LCIA for air transport and beyond where relevant.
CASE REPORT | doi:10.20944/preprints202106.0263.v1
Subject: Medicine & Pharmacology, Allergology Keywords: chronic obstructive pulmonary disease; discharge plan; leadership; multidisciplinary team; respiratory medicine; patient safety; pulmonary rehabilitation.
Online: 9 June 2021 (11:43:00 CEST)
Patients with chronic obstructive pulmonary disease (COPD) may require frequent hospitalization due to worsening symptoms. Preventing prolonged hospital stay and readmission becomes a challenge for healthcare professionals treating patients with COPD. Although the integration of health and social care supports greater collaboration and enhanced patient care, organisational structure and poor leadership may hinder the implementation of patient-oriented goals. This paper presents a case of a 64-years-old chronic smoker with severe COPD who was to be discharged on long-term oxygen therapy (LTOT). It further highlights the healthcare decisions made to ensure the patient’s safety at home, and further provide a long-lasting solution to the existing medical and social needs. The goal was accomplished through a discharge plan that reflects multidisciplinary working, efficient leadership and change management using Havelock’s theory. While COPD is characterized by frequent exacerbation and hospital readmission, it was emphasized that most failed discharge could be attributed to bureaucratic organizational workflow which might not be in the patient’s best interest. It was further demonstrated that healthcare professionals are likely to miss the window of opportunity to apply innovative and long-lasting solutions to the patient’s health condition in an attempt to remedy the immediate symptoms of COPD.
REVIEW | doi:10.20944/preprints202105.0311.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Angiotensin converting enzyme 2; breast feeding; drug therapy; pregnancy; severe acute respiratory syndrome coronavirus 2
Online: 13 May 2021 (15:26:34 CEST)
The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the chief concern of the international community in almost no time. As of May 9th, 2021, more than 150 million cases and 3.2 million deaths have been recorded. Considering the early struggle in treating COVID-19 patients, the researchers and clinicians have decided to try the previously available drugs according to their mechanisms of action. Hence, many antivirals, antibiotics, antiparasitics, and antipyretics have been proposed. Pregnant women, fetuses, and infants are known high-risk populations that are threatened during disease outbreaks. Therefore, this article reviews the safety of potential drugs for COVID-19 patients during pregnancy and breastfeeding.
BRIEF REPORT | doi:10.20944/preprints202204.0287.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; Influenza; Morbidity; Mortality; Flu; Pneumonia; Virus Infections; Preventive Medicine; Hospitalization; Internal Medicine; Respiratory illness.
Online: 29 April 2022 (04:22:05 CEST)
Abstract: Background: Our goal was to evaluate whether wearing personal protective equipment (PPE) such as an N95, or a surgical mask during the (COVID-19) pandemic had really reduced the cases of influenza in the state of Wisconsin. Methods: Respiratory Virus Surveillance Reports from the Wisconsin Department of Health Services (DHS) and the Centers for Disease Control and Prevention (CDC) were used to compare the rates of Influenza during the seasons of 2018-2019 and 2020-2021. Results: The number of cases, hospitalizations, and mortality rates with Influenza had significantly decreased in the 2020-2021 season compared to the Influenza season of 2018-2019. Discussion: Reducing the burden of influenza illnesses, hospitalizations, and deaths on the health care system is imperative. Wearing masks should be addressed for the most vulnerable.
HYPOTHESIS | doi:10.20944/preprints202004.0360.v2
Subject: Medicine & Pharmacology, Allergology Keywords: SARS-CoV-2; acute respiratory distress syndrome; hypoxic pulmonary vasoconstriction; alveolar edema; early low-flow oxygen
Online: 11 February 2021 (11:40:30 CET)
The coronavirus disease 2019 (COVID-19) has spread over the world for more than one year. COVID-19 often develops life-threatening hypoxemia. Endothelial injury caused by the viral infection leads to intravascular coagulation and ventilation-perfusion mismatch. However, besides above pathogenic mechanisms, the role of alveolar edema in the disease progression has not been discussed comprehensively. Since the exudation of pulmonary edema fluid was extremely serious in COVID-19 patients, we bring out a hypothesis that severity of alveolar edema may determine the size of poorly-ventilated area and the blood oxygen content. Treatments to pulmonary edema (alcohol-oxygen vapor therapy and fluid management) may be great helpful for reducing occurrence of severe cases. Given that late mechanical ventilation may cause mucus (edema fluid) to be blown to the deep of the small airways, oxygen therapy should be given at the early stages. The optimal time and SpO2 threshold for oxygen therapy are also discussed.
ARTICLE | doi:10.20944/preprints202101.0177.v1
Subject: Medicine & Pharmacology, Allergology Keywords: COVID-19; acute respiratory distress syndrome; methylprednisolone; mechanical ventilation; ventilator-free days; SARS-CoV-2 infection
Online: 11 January 2021 (10:13:42 CET)
Objectives: There are limited data regarding the efficacy of methylprednisolone in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation. We aimed to determine whether methylprednisolone increases the number of ventilator-free days (VFDs) among these patients. Design: Retrospective single-center study Setting: Intensive care unit Patients: All patients with ARDS due to confirmed SARS-CoV-2 infection and requiring invasive mechanical ventilation between 1 March and 29 May 2020 were included Interventions: None Measurements and Main Results: The primary outcome was ventilator-free days (VFDs) during the first 28 days, defined as being alive and free from mechanical ventilation. The primary outcome was analyzed with competing-risks regression based on Fine and Gray’s proportional subhazards model. Death before day 28 was considered to be the competing event. A total of 77 patients met the inclusion criteria. Thirty-two patients (41.6%) received methylprednisolone. The median dose was 1 mg.kg-1 (IQR: 1-1.3 mg.kg-1) and median duration of 5 days (IQR:5-7 days). Patients who received methylprednisolone had a mean 18.8 VFDs (95% CI, 16.6-20.9) during the first 28 days vs. 14.2 VFDs (95% CI, 12.6-16.7) in patients who did not receive methylprednisolone (difference, 4.61; 95% CI, 1.10-8.12; P = 0.001). In the multivariable competing-risks regression analysis and after adjusting for potential confounders (ventilator settings, prone position, organ failure support, severity of the disease, tocilizumab, and inflammatory markers), methylprednisolone was independently associated with a higher number of VFDs (subhazards ratio: 0.10, 95%CI: 0.02-0.45; p=0.003). Hospital mortality did not differ between the two groups (31.2% vs. 28.9%, p=0.82). Hospital length of stay was significantly shorter in the methylprednisolone group (24 days [IQR:15-41 days] vs. 37 days [IQR:23-52 days], p=0.046). The incidence of positive blood cultures was higher in patients who received methylprednisolone (37.5% vs. 17.8%, p=0.052). However, 91% of patients who received methylprednisolone also received tocilizumab. The number of days with hyperglycemia was similar in the two groups. Conclusions: Methylprednisolone was independently associated with increased VFDs and shortened hospital length of stay. The combination of methylprednisolone and tocilizumab was associated with a higher rate of positive blood cultures. Further trials are needed to evaluate the benefits and safety of methylprednisolone in moderate or severe COVID-19 ARDS.
BRIEF REPORT | doi:10.20944/preprints202003.0338.v3
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: Severe Acute Respiratory Syndrome Coronavirus-2; (soluble) ACE2; eosinophil; asthma; IL-10; Lung fibrosis; hypercapnic acidosis; hypoxia; infarction; hypertension; cardiac dysfunction; respiratory distress; coagulopathy; Angiotensin; renin; Ang (1-7); Ang (1-9); Mas receptor; AT2 receptor
Online: 6 May 2020 (04:40:25 CEST)
The article describes the rational for inhibition of the angiotensin-converting enzyme 2 (ACE2) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent the establishment of positive feedback loops triggered by COVID-19 in some predisposed subjects. Making use of a large quantity of published reports in which human/rodent ACE2 pathway inhibitors were administered in vivo, it is hypothesized a possible therapeutic pharmacological intervention through an inhibition strategy of the zinc metalloprotease ACE2 and its downstream pathway for SARS-CoV-2 patients. Of even more interest, metal (zinc) chelators and renin inhibitors (both FDA approved drugs) may also work alone or in combination in inhibiting the positive feedback loops, initially triggered by COVID-19 and subsequently sustained by hypoxia independently on viral trigger, when both arms of renin-angiotensin system (ACE2 and ACE) are upregulated, leading to critical, advanced and untreatable stages of the disease.
ARTICLE | doi:10.20944/preprints202208.0535.v1
Subject: Life Sciences, Virology Keywords: mumps; parotitis; parotid gland extenstion; salivary gland; respiratory virus; human herpesvirus 4 (HHV4); human herpesvirus 6 (HHV6)
Online: 31 August 2022 (07:11:53 CEST)
Mumps is the second-most reported infectious disease in South Korea; however, due to the low pathogen confirmation rate in laboratory diagnoses, we proposed a method for reevaluating the high incidence rate via the laboratory verification of other viral diseases. In 2021, 63 cases of pharyngeal or cheek mucosal swabs of suspected mumps cases in Gwangju, South Korea, were assessed for causative pathogens using massive simultaneous pathogen testing (TaqManTM Array Cards). More than one respiratory virus was detected in 60 cases (95.2%), 44 (73.3%) of which were co-detected. Human rhinovirus was detected in 47 cases, followed by human herpesvirus (HHV)6 in 30; HHV4 (17), human bocavirus (17), HHV5 (10), and human parainfluenza virus 3 (6) were also detected. Our findings suggest the need for further investigations on the pathogenesis of diseases mimicking mumps, which are considered to aid with appropriate public health responses, treatment, and the prevention of infectious disease outbreaks.
ARTICLE | doi:10.20944/preprints202103.0068.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: air purification; animal production; porcine reproductive and respiratory syndrome; livestock health,; livestock biosecurity; swine diseases; ultraviolet light
Online: 2 March 2021 (10:08:23 CET)
Proper treatment of infectious air could potentially mitigate the spread of airborne viruses such as porcine reproductive and respiratory syndrome virus (PRRSV). The objective of this research is to test the effectiveness of ultraviolet (UV) in inactivating aerosolized PRRSV, specifically, four UV lamps, UV-A (365 nm, both fluorescent and LED-based), "excimer" UV-C (222 nm), and germicidal UV-C (254 nm), were tested. The two UV-C lamps effectively irradiated fast-moving PRRSV aerosols with short treatment times (<2 s). One-stage and two-stage UV inactivation models estimated the UV doses needed for target percentage (%) reductions on PRRSV titer. UV-C (254 nm) dose needed for 3-log (99.9%) reduction was 0.521 and 0.0943 mJ/cm2, respectively, based on one-stage and two-stage models. An order of magnitude lower UV-C (222 nm) doses were needed for a 3-log reduction, i.e., 0.0882 and 0.048 mJ/cm2, based on one-stage and two-stage models, respectively. However, the cost of 222-nm excimer lamps is still economically prohibitive for scaling-up trials. The UV-A (365 nm) lamps could not reduce PRRSV titers for tested doses up to 4.11 mJ/cm2. Pilot-scale or farm-scale testing of UV-C on PRRSV aerosols simulating barn ventilation rates are recommended based on its effectiveness and reasonable costs comparable to HEPA filtration.
REVIEW | doi:10.20944/preprints202012.0519.v1
Subject: Life Sciences, Genetics Keywords: MLS/MIDAS/LSDMCA, X-inactivation, HCCS/COX7B/NDUFB11, mitochondrial disorders, mitochondrial respiratory chain, microphthalmia, linear skin defects
Online: 21 December 2020 (12:03:53 CET)
Mitochondrial disorders, although heterogeneous, are traditionally described as conditions characterized by encephalomyopathy, hypotonia and progressive postnatal organ failure. Here we provide a systematic review of Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA), a rare unconventional mitochondrial disorder which presents as a developmental disease; its main clinical features include microphthalmia with different degrees of severity, linear skin lesions, and central nervous system malformations. The molecular basis of this disorder has been elusive for several years. Mutations were eventually identified in three X-linked genes, i.e., HCCS, COX7B, and NDUFB11, which are all endowed with defined roles in the mitochondrial respiratory chain. A peculiar feature of this condition is its inheritance pattern: X-linked dominant male-lethal. Only female or XX male individuals can be observed, implying that nullisomy for these transcripts is incompatible with normal embryonic development in mammals. All three genes undergo X-inactivation that, according to our hypothesis, may contribute to the extreme variable expressivity observed in this condition. We propose that mitochondrial dysfunction should be considered as an underlying cause in developmental disorders. Moreover, LSDMCA should be taken into consideration by clinicians when dealing with patients with microphthalmia with or without associated skin phenotypes.
REVIEW | doi:10.20944/preprints202008.0035.v1
Subject: Medicine & Pharmacology, Other Keywords: Experimental radiotherapy; radiobiology; Mesenchymal stem cells; Cell therapy; Exosome; Annexin A1; Acute-respiratory-distress-syndrome; COVID-19
Online: 2 August 2020 (14:54:24 CEST)
Previously we have shown that the combination of radiotherapy with human-umbilical-cord-derived mesenchymal stem-cell therapy significantly reduces the size of the xenotumours in mice, both in the directly irradiated tumour and in the distant non-irradiated tumour or in its metastasis. We have also shown that exosomes secreted from mesenchymal stem-cells pre-irradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from non-irradiated mesenchymal cells and also that proteins, exosomes and microvesicles secreted by mesenchymal cells suffer a dramatic change when cells are activated or non-activated, with the amount of protein present in the exosomes of the pre-irradiated cells being 1.5-fold times greater compared to those from non-irradiated cells. This finding correlates with a dramatic increase in the anti-tumour activity of the exosomes secreted by pre-irradiated mesenchymal-cells. After the proteomic analysis of the load of the exosomes released from both irradiated and non-irradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation which is characteristic of acute-distress-respiratory syndrome, we have designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by COVID-19, require the care of an intensive care unit for patients with life-threatening conditions. With this hypothesis, we would seek to improve the patients’ respiratory capacity and increase the expectations of their cure.
HYPOTHESIS | doi:10.20944/preprints202003.0319.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; coronavirus; SARS-CoV-2; respiratory illness; pneumonia; I4R approach; immune system; inflammation; immune boosting interventions
Online: 23 March 2020 (00:33:02 CET)
The current global pandemic of coronavirus disease 2019 (COVID-19) caused by the coronavirus SARS-CoV-2 has already had a major adverse impact on the world due to the exponentially increasing deaths due to the disease and the extreme actions taken by the world community to prevent its spread. It is important to explore novel methods of reducing the illnesses and fatality rates of the coronavirus-infected patients. Since the weakness of the immune system is one of the major contributing factors for the illnesses caused by such viruses, and since inflammation is a major contributing factor for the mortality of COVID-19 patients, interventions that boost the immune system and/or are anti-inflammatory may reduce the COVID-19 incidence and the mortality due to the disease. A large variety of interventions are known to improve the immune response and/or reduce inflammation. However, all the interventions would not be applicable or acceptable to everyone and so the interventions would need to be individualized based on individual circumstances and preferences. This approach, known as “Individualized Interventions to Improve the Immune Response”, or the I4R approach, should be studied in pilot clinical trials urgently, in order to potentially reduce the harm caused by the current coronavirus pandemic.
REVIEW | doi:10.20944/preprints201811.0475.v1
Subject: Biology, Other Keywords: Mononegavirales; Chaperones; Antivirals; Hsp70; Hsp90; CCT; Respiratory syncytial virus; Measles virus; Mumps Virus; Rabies virus; Ebola virus.
Online: 19 November 2018 (17:22:51 CET)
The order Mononegavirales harbors numerous viruses of significant relevance for human health, including both established and emerging infections. Currently, vaccines are only available for a small subset of these viruses and antiviral therapies remain limited. Being obligate cellular parasites, viruses must utilize the cellular machinery for their replication and spread. Therefore, targeting cellular pathways used by viruses can provide novel therapeutic approaches. One of the key challenges confronted by both hosts and viruses alike is the successful folding and maturation of proteins. In cells, this task is faced by cellular molecular chaperones, a group of conserved and abundant proteins that oversee protein folding and help maintain protein homeostasis. In this review, we summarize the current knowledge of how the mononegavirales interact with cellular chaperones, highlight key gaps in our knowledge, and discuss the potential of chaperone inhibitors as antivirals.
REVIEW | doi:10.20944/preprints202107.0367.v1
Subject: Biology, Anatomy & Morphology Keywords: Fever; Beneficial fever; Infections; WHO; Fever Management; Guidelines; Antipyretic; Mortality; Heat Shock; Inflammation; COVID-19; Respiratory diseases; Paracetamol
Online: 16 July 2021 (09:40:35 CEST)
Fever remains an integral part of the acute clinical diseases management, esp. viral, for which effective therapeutics remain desired. However, the presence of often confusing fever reduction recommendations for COVID-19 in the public domain during the pandemic, as late as 28 April 2021, seems to suggest the reduction of any ‘uncomfortable’ fever ranging from 37.8 - 39oC, as opposed to WHO fever reduction guidelines (≥39oC), urgently need attention. The confusion could percolate down into different agencies who look up to these agencies for guidance in framing their own, denying the benefits of fever to populations, and effectively undo whatever successive WHO’s guidelines have achieved in the last two decades. The existence of conflicting guidelines in public domains which are open to interpretations has consequences to public health and the healthcare infrastructure, on implementation. For controlling acute infectious diseases, esp. viral, the fever remains the most important enabler. Historically, our chief obstacles to harnessing the benefits of fever in acute clinical diseases with limited therapeutics had been: a) widespread myths about ‘fevers’ arising from a general misunderstanding of basic facts; b) presence of confusing guidelines by different agencies which are open to alternate interpretation. The article attempts to briefly indicate the benefits of fever in disease resolution, dispel myths, underline vagueness in illustrative national guidelines and the need to align them with evidence-based WHO guidelines, as it has the potential to perpetuate myths/confusion in masses leading to adverse impact on disease management – more morbidity and mortality from diseases including COVID-19.
ARTICLE | doi:10.20944/preprints202105.0011.v1
Subject: Life Sciences, Biochemistry Keywords: Annocatacin B; ND1 Subunit; Mitochondrial Respiratory Complex I; MRC-I; Molecular Dynamics Simulations; MD; Hirshfeld Charges; MM/PBSA
Online: 3 May 2021 (16:13:49 CEST)
ND1 subunit possesses the majority of the inhibitor binding domain of the human MRC-I. This is an attractive target for the search for new inhibitors that seek mitochondrial dysfunction. It is known, from in vitro experiments, some metabolites from Annona muricata called acetogenins have important biological activities such as anticancer, antiparasitic, and insecticide. Previous studies propose an inhibitory activity of bovine MRC-I by bis-THF acetogenins such as annocatacin B, however, there are few studies on its inhibitory effect on human MRC-I. In this work, we evaluate the molecular and energetic affinity of the annocatacin B molecule with the human ND1 subunit in order to elucidate its potential capacity to be a good inhibitor of this subunit. For this purpose, QM optimizations, MD simulations and MM/PBSA analysis were performed. As a control to compare our outcomes, the molecule rotenone, which is a known MRC-I inhibitor, was chosen. Our results show that annocatacin B has a greater affinity for the ND1 structure, its size and folding were probably the main characteristics that contributed to stabilize the molecular complex. Furthermore, the MM/PBSA calculations showed a 35% stronger BFE compared to the rotenone complex. Detailed analysis of the BFE shows that the aliphatic chains of annocatacin B play a key role in molecular coupling by distributing favorable interactions throughout the major part of the ND1 structure. These results are consistent with experimental studies that mention that acetogenins may be good inhibitors of MRC-I.