ARTICLE | doi:10.20944/preprints202108.0395.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Organizing pneumonia; Cryptogenic organizing pneumonia; Secondary organizing pneumonia
Online: 19 August 2021 (10:22:38 CEST)
Organizing pneumonia (OP) can be diagnosed pathologically, and cryptogenic OP (COP) and secondary OP (SOP) have been classified by cause and underlying context. Because it is clinically difficult to differentiate between COP and SOP, this study investigated characteristics that could distinguish between COP and SOP. The medical records of patients who underwent lung biopsy from 2016 to 2018 were retrospectively reviewed. Eighty-five patients had pathologically proven OP, including 16 diagnosed with COP and 69 diagnosed with SOP. The most common cause of SOP was infectious pneumonia, observed in 57 (82.6%) of the 69 patients. Median time from symptom onset to hospital admission is shorter (P=0.006) and fever was more common (P=0.021) in the SOP. Some laboratory results differed significantly between the two groups. Lymphocyte in bronchoalveolar lavage fluid were higher in the COP (P=0.012). Radiologic findings showed that effusion was more common in the SOP (P=0.043). There were no between-group differences in steroid use, 30 day and in-hospital mortality rates, and rates of OP outcomes and recurrences. Infection is the main cause of SOP. Symptom onset is more rapid in patients with SOP. Pleural effusion was more common in the SOP but there were no differences in clinical course.
ARTICLE | doi:10.20944/preprints201906.0183.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: sepsis; community-acquired pneumonia; very old, pneumonia
Online: 19 June 2019 (10:00:15 CEST)
Background: Little is known about risk and prognostic factors in very old patients developing sepsis secondary to community-acquired pneumonia (CAP). Methods: We conducted a retrospective observational study of data prospectively collected at the Hospital Clinic of Barcelona over a 13-year period. Consecutive patients hospitalized with CAP were included if they were very old (≥80 years) and divided into those with and without sepsis for comparison. Sepsis was diagnosed based on the Sepsis-3 criteria. The main clinical outcome was 30-day mortality. Results: Among the 4,219 patients hospitalized with CAP during the study period, 1,238 (29%) were very old. The prevalence of sepsis in this aged group was 71%. Male sex, chronic renal disease, and diabetes mellitus were independent risk factors for sepsis, while antibiotic therapy before admission was independently associated with a lower risk of sepsis. Thirty-day and intensive care unit (ICU) mortality did not differ between patients with and without sepsis. In CAP-sepsis group, chronic renal disease and neurological disease were independent risk factors for 30-day mortality. Conclusion: In very old patients hospitalized with CAP, in-hospital and 1-year mortality rates were increased if they developed sepsis. Antibiotic therapy before hospital admission was associated with a lower risk of sepsis.
ARTICLE | doi:10.20944/preprints201809.0186.v1
Subject: Mathematics & Computer Science, Applied Mathematics Keywords: malaria; mass action; malaria-pneumonia; optimal control; pneumonia
Online: 11 September 2018 (08:01:51 CEST)
Malaria and Pneumonia are leading causes of serious illness in children and adults worldwide with their death rate and prevalence on the rise. Such alarming statistics may retard the milestones so far achieved in meeting the Millennium Development Goals 4 and 6 whose targets are to improve child survival and reverse the high prevalence of diseases such as pneumonia and malaria respectively. Two sub-models of malaria-pneumonia co-infection namely malaria model and pneumonia model were considered first and then followed by the full malaria-pneumonia co-infection model. The malaria model, pneumonia model and co-infection model basic reproduction numbers denoted by Rm, Rp and Rmp respectively was obtained using the Next Generation Matrix method. The model disease free equilibrium’s local and global stability was analysed using Descartes’ Rule of signs and Comparison method. The bifurcation analysis for the malaria, pneumonia and co-infection models was studied using the Centre Manifold Theory. The sensitivity indices of the model basic reproduction numbers Rm, Rp and Rmp to the parameters in the models were calculated. Optimal control theory was applied using the Pontryagins’ Maximum Principle to investigate optimal strategies for controlling the spread of malaria, pneumonia and co-infection models using insecticide treated bed nets (u1(t)) spraying of mosquitoes insecticides (u2(t)), sanitation (u3(t)), vaccination (u4(t)), anti-malaria drugs (u5(t)), anti-pneumonia drugs (u6(t)), both anti-malaria drugs and anti-pneumonia drugs (u7(t)) as the system time control variables. Numerical simulations using a set of parameter values were provided to validate the analytical results.
REVIEW | doi:10.20944/preprints202009.0067.v1
Online: 3 September 2020 (09:29:32 CEST)
Background: The reported associations between time to first antibiotic dose after hospital arrival and short-term mortality have varied in prior studies of CAP. It is unclear the benefit of early antibiotics in all patients given the risks of antibiotic overuse and misdiagnosis; Methods: A PubMed and Google Scholar search was performed to identify articles detailing the epidemiology, prognosis, diagnosis, and preliminary management of CAP; Results: In sepsis, antibiotics should not be delayed, and should be administered as soon as possible after recognition. For moderate or severe CAP patients without sepsis, antibiotics should be administered as soon as the diagnosis of CAP is highly likely. For stable, non–critically ill patients with CAP, the timing of antibiotics is not as clear and available evidence does not recommend strict requirements. Antibiotic timing – both rapid and delayed could be used as indicators of quality care in differing clinical scenarios; Results: The dogma of starting antibiotics quickly, within a rigid timeframe of expectations and guidelines has not improved outcomes in pneumonia patients, and has led to an increase in antibiotic treatment in uninfected patients. Severity of illness is the key factor associated with poor outcomes and should more significantly guide the timing of antibiotic initiation.
ARTICLE | doi:10.20944/preprints201906.0236.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: cefotaxime; pneumonia; bacteremia; outcomes
Online: 24 June 2019 (09:02:55 CEST)
Background: We aimed to analyze the impact of cefotaxime non-susceptibility on the 30-day mortality rate in patients receiving a third-generation cephalosporin for pneumococcal bacteremic pneumonia. Methods: We conducted a retrospective observational study of prospectively collected data from the Hospital Clinic of Barcelona. All adult patients with monomicrobial bacteremic pneumonia due to Streptococcus pneumoniae and treated with a third-generation cephalosporin from January 1991 to December 2016 were included. Risk factors associated with 30-day mortality were evaluated by univariate and multivariate analyses. Results: During the study period, 721 eligible episodes were identified, and data on the susceptibility to cefotaxime was obtainable for 690 episodes. Sixty six (10%) cases were due to a cefotaxime non-susceptible strain with a 30-day mortality rate of 8%. Variables associated with 30-day mortality were age, chronic liver disease, septic shock, and the McCabe score. Infection by a cefotaxime non-susceptible S. pneumoniae did not increase the mortality rate. Conclusion: Despite the prevalence of cefotaxime non-susceptible S. pneumoniae has increased in recent years. We found no evidence to suggest that patients hospitalized with bacteremic pneumonia due to these strains had worse clinical outcomes than patients with susceptible strains.
HYPOTHESIS | doi:10.20944/preprints202004.0348.v3
Subject: Medicine & Pharmacology, General Medical Research Keywords: hydroxychloroquine; COVID-19; pneumonia; prophylaxis; treatment
Online: 12 May 2020 (08:06:55 CEST)
According to current literature and preliminary data, hydroxychloroquine (HCQ) seems potentially effective in the treatment of patients with Covid-19 pneumonia. The concentrations of HCQ in lungs might be well above that of plasma. Most likely, this property of HCQ provides effective drug concentrations in lungs. HCQ has a gradual onset of action in the treatment of rheumatic diseases. This could be valid for the treatment of Covid-19 pneumonia. It was suggested that regular HCQ administration in animals for a certain time might result in gradual accumulation of HCQ in tissues. Reduced perfusion, somewhat distorted architecture of lung tissue, edema and, suggested gradual accumulation of HCQ in lung tissue might cause reduced HCQ concentrations in pneumonic areas of the lungs in Covid-19 pneumonia. Patients with Covid-19 pneumonia and extensive lung involvement might have less HCQ concentrations in their lungs than patients having limited lung involvement. Furthermore, patients with Covid-19 pneumonia and extensive lung involvement might have more viral load than patients having limited lung involvement. That’s why treatment of patients with advanced Covid-19 pneumonia using HCQ might result in treatment failure, however HCQ might be effective in the treatment of patients with mild and moderate Covid-19 pneumonia. Using HCQ in Covid-19 pneumonia prophylaxis seems logical since providing enough accumulation of HCQ in the healthy lungs, before the arrival of the SARS-CoV-2 virus, might prevent Covid-19 pneumonia. However, the purpose of this paper is not to recommend using or not using HCQ for the treatment or for the prophylaxis of Covid-19 pneumonia. The purpose of this paper is only to try to bring a new perspective on the role of HCQ in the treatment or in the prophylaxis of Covid-19 pneumonia. This paper proposes only hypotheses, which need further researches to be confirmed.
REVIEW | doi:10.20944/preprints202104.0031.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Community-Acquired Pneumonia; Hospital-Acquired Pneumonia; COVID-19; Antibiotics; Mes-enchymal Stem Cells; Corticosteroids
Online: 1 April 2021 (16:18:25 CEST)
Pneumonia remains a major cause of morbidity and mortality worldwide, especially during COVID-19 pandemic. With the significant global health burden that pneumonia poses, it is es-sential to improve therapeutic and management strategies. The increasing emergence of antibiotic resistant bacterial strains limits options for effective antibiotic use. New antibiotics for treatment of pneumonia may address deficits in current antimicrobial drugs, with an ability to cover both typical, atypical, and resistance pathogen. Several of these newer drugs also have structural characteristics that allow for a decreased propensity in development of bacterial resistance. Po-tential use of stem cell therapies in place of corticosteroid treatments may also offer an im-provement in patient outcomes. Human mesenchymal stem cell treatments have shown efficacy and safety in treating COVID-19 induced pneumonia. Combined treatment with both stem cells and antibiotics in pneumonia in a rabbit model has also shown significantly increased efficacy in comparison to antibiotic treatment alone, presenting yet another possible route for a novel strategy in treating pneumonia, though additional future studies are necessary before clinical implementation. While pneumonia remains a major disease of concern, having newer approved antibiotics as well as novel therapies such as stem cell treatments in the pipeline offers clinicians more options in effectively treating pneumonia.
ARTICLE | doi:10.20944/preprints202203.0072.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: antibiotic resistance; Acinetobacter baumannii; severe pneumonia
Online: 4 March 2022 (03:15:35 CET)
Background: Patients hospitalized in the intensive care unit (ICU) have a higher susceptibility to infections. Respiratory infections are the most common nosocomial infections. Rising antibiotic resistance due to indiscriminate use of antibiotics and poor adherence to standard precaution in healthcare facilities compounds the problem. The main aim of this study is to assess microbial patterns and antibiotic resistance from bronchoalveolar lavage specimens in severe pneumonia patients. Methods: This retrospective study was conducted in an Indonesian tertiary care hospital from January 2016-December 2020. Written and verbal informed consent was obtained prior to bronchoscopy procedures. Patients were enrolled if they had severe community-acquired pneumonia (CAP) according to American Thoracic Society (ATS)/Infectious Disease Society of America (IDSA) criteria, had high-risk hospital-acquired pneumonia (HAP), late-onset ventilator-associated pneumonia (VAP), or pneumonia caused by Coronavirus disease (COVID-19). Respiratory specimens via bronchoscopy were inoculated on general semi-sloid thioglycolate media. Testing for antibiotic susceptibility was done using the disk diffusion method. Results: Two hundred and one patients’ data were analyzed. The majority of patients were males (65,17%) and above 60 years of age. The most common type of pneumonia was CAP (39,3%). Neurologic/cerebrovascular disease was the most common comorbidity (35,32%). Acinetobacter baumannii was the most frequently isolated microorganism. Ampicillin/sulbactam and amikacin were found to yield lower microbial resistance. Conclusion: Combination of ampicillin/sulbactam and amikacin appeared effective as initial empirical therapy in severe pneumonia patients. Further studies are needed to evaluate the feasibility and effectiveness of this combined therapy.
BRIEF REPORT | doi:10.20944/preprints202005.0482.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: COVID19; preterm neonate; pneumonia; vertical transmission
Online: 31 May 2020 (16:39:43 CEST)
We report the first case of COVID 19 pneumonia in a preterm neonate in Mayotte, an overseas department of France. The respiratory distress with typical thoracic imaging lesions appears at 14 days of life. This case-report emphasizes the need for a cautious and close up follow-up for asymptomatic neonates born to mothers with COVID-19 infection. Vertical transmission cannot be excluded in this case.
REVIEW | doi:10.20944/preprints202002.0358.v3
Subject: Life Sciences, Virology Keywords: Infectious diseases; Coronavirus; SARS-CoV-2; COVID-19; Pneumonia; China
Online: 28 February 2020 (13:21:43 CET)
The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) linked with coronavirus disease 2019 (COVID-19) poses a serious threat to public health worldwide. Firstly, the SARS-CoV-2 was reported in Wuhan, Hubei Province, China in December 2019. Initially, the major proportion of virus-infected cases (i.e. about 99%) was reported in China and now it is being reported in other counties as well. Humans begin to be infected within their communities and transmittance of the viral epidemic increased rapidly due to lack of understanding of its transmission routes and precautionary measures. The existence of SARS-CoV-2 in China threatened the population greatly due to the high incidence of fatal respiratory infections. Current investigations speculated that this virus transferred into a human from viral-infected bats. However, the process of interspecies viral transmission is an important scientific question to be addressed. Due to the continuous increase in the patients infected with COVID-19 associated pneumonia, the World Health Organization (WHO) has included this viral epidemic to the priority list of diseases. Therefore, accelerated research developments are required to control the spread of this outbreak, as it is declared as a public health emergency by WHO especially in the absence of efficacious drugs and vaccines. Our review encompasses the recent status of disease severity in China, a particular replication mechanism of SARS-CoV-2 and potential risks and precautionary measures required to avoid contact with this fatal viral infection.
CASE REPORT | doi:10.20944/preprints201609.0045.v1
Subject: Medicine & Pharmacology, Other Keywords: eosinophilic pneumonia; lung nodules; dyspnea; eosinophils
Online: 13 September 2016 (04:04:39 CEST)
Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterized by an abnormal and marked accumulation of eosinophils in the interstitial and alveolar spaces of the lung. Idiopathic chronic eosinophilic pneumonia is reported to comprise anywhere from 0-2.5% of cases within the registries of interstitial lung disease. Diagnosis is based on the clinical constellation of symptoms, characteristic radiographic findings and peripheral blood or BAL eosinophilia, in the absence of infection or drug-induced eosinophilia. There is no consensus on the dose and duration of treatment, but most authors recommend initial doses of prednisone at 0.5–1 mg/kg/day with gradual tapering of the dose for total treatment duration of 6–12 months.
ARTICLE | doi:10.20944/preprints202111.0210.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: CRISPR-Cas, Nucleic acid detection, Klebsiella pneumonia
Online: 11 November 2021 (12:57:06 CET)
Klebsiella pneumonia (K. pneumoniae) is a Gram-negative bacterium that causes nosocomial infections in the lung, bloodstream, and urinary tract. Therefore, detecting K. pneumoniae in early time is important in preventing severe infections. However, clinical detection of K. pneumoniae requires a long time of agar plate culture. Nucleic acid detection like qPCR is precise but requires expensive equipment. Recent research reveals that collateral cleavage activity of CRISPR-LbCas12a has been applied in nucleic acid detection. In this study, PCR combined with CRISPR-LbCas12a targeting the K. pneumoniae system was established. This system showed excellent detection specificity and sensitivity in both bench work and clinical samples. Due to its advantages, its application can meet different detection requirements in health centers where qPCR is not accessible.
ARTICLE | doi:10.20944/preprints202105.0711.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: pneumonia; Resnet; residual; PEPX-Resnet; COVID-19
Online: 31 May 2021 (08:29:00 CEST)
Pneumonia is a leading cause of death worldwide, and one of the most significant approaches to diagnose pneumonia is Chest X-ray (CXR) since it was used in clinical scenes. Convolutional neural networks (CNNs) have been widely used in computer vision community. Along with the development of CNNs, we want to make use of CNNs to recognize CXR of people who get pneumonia and make classification. It is important, especially during epidemic period. In this paper, we present a new type of residual learning framework, PEPX-Resnet, which makes use of a type of lightweight residual, and apply this network to CXR dataset. The result shows that PEPX-Resnet is easier to optimize and can have better results, especially for COVID-19 cases. PEPX-Resnet could reach higher accuracy, f1 score and some other evaluations for CXR dataset.
REVIEW | doi:10.20944/preprints202105.0563.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Community-acquired pneumonia; incidence; prophylaxis; pneumococcal; vaccination
Online: 24 May 2021 (10:52:36 CEST)
Current epidemiological data reports that adults aged 65 years and older comprise the most vulnerable age group with the highest proportion of CAP-attributable hospitalizations. Pneumococcal vaccine efficacy (VE) has been shown to decrease over time, contributing to increasing incidence rates of CAP. A holistic evaluation of age, sex, seasonality, and VE are is conducted in this systematic review and meta-analysis of 12 prospective and retrospective cohort studies. The findings suggest that incidence and age are positively associated and that incidence in females is more often reported to be higher in females than in males. In studies that observed seasonality of CAP, high seasons and low seasons were reported to be in winter and summer months, respectively. Lastly, studies that reviewed the effect of vaccination on incidence consistently found decreased observance of CAP in elderly adults following reception of PCV13 or PPSV23. However, one study suggested that such vaccinations may have decreased effectiveness in elderly populations and that research examining potential explanations for this require further investigation. Furthermore, distinct diagnostic and case ascertainment standards, descriptive measures, and methods of prevention and treatment of CAP used across the US are outlined in this review. Public health guidance such as encouraging the reception of pneumococcal vaccinations and mask-wearing during high seasons of CAP, and communicating the risks of not adhering to the aforementioned preventative measures can facilitate an effort to reduce the incidence of CAP and its associated adverse outcomes in the US elderly population.
ARTICLE | doi:10.20944/preprints202002.0132.v2
Subject: Life Sciences, Virology Keywords: 2019-nCoV; SARS-CoV-2; novel corona virus; Wuhan pneumonia
Online: 18 February 2020 (11:52:25 CET)
The rapid development of 2019-2020 Wuhan seafood market pneumonia currently posed a major public health concern in China. Genome sequencing identified a novel beta-coronavirus closely related to SARS-CoV, named 2019-nCoV by WHO, as the cause of this pandemic disease. Viruses with single stranded RNA genome are prone to evolve quickly by accumulation of mutations, such as SNV, INDEL and cross viral recombination, aiding fast transmission among hosts and cross species. Here we collected related genome sequences and investigated variations shared by different strains of 2019-nCoV, identified reoccurrence of SNV mutations in clusters of patients, an indication of rapid evolution of 2019-nCoV at the transmission from animal host to human. The information collected herein would help to understand the dynamics of current pandemic.
ARTICLE | doi:10.20944/preprints201906.0024.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: adenovirus; pneumonia; fever; response to antipyretic treatment
Online: 3 June 2019 (14:02:51 CEST)
In 2014, the outbreak of adenoviral pneumonia occurred in Korean military training center. However, there is limited data on characteristics of fever and its response to antipyretics therapy in immunocompetent adults with adenoviral positive community-acquired pneumonia (CAP). Medical records of patients who were admitted to Armed Forces Chuncheon Hospital for treatment of CAP between January 2014 and December 2016 were retrospectively analyzed. We evaluated demographics, clinico-laboratory findings and radiologic findings at admission were compared between adenovirus positive (Adv) group and adenovirus negative (non-Adv) group. Out of 251 military personnel with CAP during the study periods, 67 were classified into Adv group while 184 were Non-Adv group. Patients with Adv group had a longer duration of fever after admission and symptom onset. Adv group patients had a higher mean temperature at admission and more observed over 40 and 39 to 40℃. Adv group patients had more commonly observed no response to antipyretic treatment and adverse events after antipyretics use. Length of hospital stay had no significant difference between two groups and no patient died in both groups. In our study, Adv positive CAP in patients with immunocompetent military personnel had distinct characteristics of fever and response to antipyretic treatment.
ARTICLE | doi:10.20944/preprints202004.0243.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: vitamin C; ascorbic acid; ascorbate; pneumonia; community acquired pneumonia; oxidative stress; protein carbonyls; hypovitaminosis C; vitamin C deficiency
Online: 15 April 2020 (10:12:26 CEST)
Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the intensive care unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and haematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, a marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs 56 ± 24 µmol/L, P <0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs 24 ± 14 µmol/L, P = 0.02). The total pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (P < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples form 28% of the cohort (mean 2.7 ± 1.7 days; range 1-7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (P = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Due to the important roles that vitamin C plays in the immune system, low vitamin C status is possibly both a cause and a consequence of the disease. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease oxidative stress and aid in their recovery.
ARTICLE | doi:10.20944/preprints202201.0264.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: pediatric pneumonia; hospital readmission; healthcare quality; hospital costs
Online: 18 January 2022 (16:08:11 CET)
Pneumonia is the leading cause of hospitalization in pediatric patients. Disease severity greatly influences pneumonia progression and adverse health outcomes such as hospital readmission. Hospital readmissions have become a measure of healthcare quality to reduce excess expenditures. The aim of this study was to examine 30-day all-cause readmission rates and evaluate the association between pneumonia severity and readmission among pediatric pneumonia hospitalizations. Using 2018 Nationwide Readmissions Database (NRD), we conducted a cross-sectional study of pediatric hospitalizations for pneumonia. Pneumonia severity was defined by the presence of respiratory failure, sepsis, mechanical ventilation, dependence on long-term supplemental oxygen, and/or respiratory intubation. Outcomes of interest were 30-day all-cause readmission, length of stay, and cost. The rate of 30-day readmission for the total sample was 5.9%, 4.7% for non-severe pneumonia, and 8.7% for severe pneumonia (p<0.01). Among those who were readmitted, hospitalizations for severe pneumonia had a longer length of stay (6.5 vs. 5.4 days, p<0.01) and higher daily cost ($3,246 vs. $2,679, p<0.01) than admissions for non-severe pneumonia. Factors associated with 30-day readmission were pneumonia severity, immunosuppressive conditions, length of stay, and hospital case volume. To reduce potentially preventable readmissions, clinical interventions to improve the disease course and hospital system interventions are necessary.
CASE REPORT | doi:10.20944/preprints202007.0398.v1
Online: 17 July 2020 (16:02:28 CEST)
The pandemic respiratory disease COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan in December 2019 and then spread throughout the world; Italy was the most affected European country. Despite the close pet-human contact, little is known about the predisposition of pets to SARS-CoV-2. Among these, felines are the most susceptible. In this study, a domestic cat with clear symptoms of pneumonia, confirmed by Rx imaging, was found to be infected by SARS-CoV-2 using quantitative RT–qPCR from a nasal swab. This is the first Italian study reporting on the request of the scientific community to focus attention on the possible role of pets as a SARS-CoV-2 reservoir. An important question remains unanswered: did the cat die from SARS-CoV-2 infection?
ARTICLE | doi:10.20944/preprints202005.0483.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: Lung CT; imaging; COVID-19; Pneumonia; Heart Failure
Online: 31 May 2020 (16:49:04 CEST)
Background: Lung CT provides an effective modality to evaluate patients with suspected COVID-19. However, overlapping imaging findings with cardiogenic pulmonary oedema have been reported. Reports comparing lung CT features of these diseases have not been elaborated. Thus, we aimed to investigate these gaps in the knowledge regarding low-dose lung CT features of patients with COVID-19 pneumonia with those with acute heart failure (HF). Methods: This retrospective analysis enrolled hospitalized patients with COVID-19 (n=10) and acute heart failure (n=9) that exclusively underwent low-dose lung CT scans within 24-hours of admission. Clinical and lung CT characteristics were collected and analysed. Results: Ground-glass-opacities (GGO) appearance has been recorded in all subjects in HF and COVID-19 group. There was no significant statistical difference between the two groups for rounded morphology, consolidation, crazy paving pattern, lesion distribution, parenchymal band (P> 0.05). However, diffuse lesions were more frequent in HF cases (55.6% vs. 0%) than in COVID-19 pneumonia, which had predominantly multifocal pattern. Notably, CT images in HF patients were more likely to have signs of interstitial tissue thickening such as the interlobular septums, fissures and peribronchovascular interstitium (55.6% vs 0%, 88.9% vs 20% and 44.4% vs 0%,respectively), as well as cardiomegaly (77.8% vs 0%), increased artery to bronchus ratio (55.6% vs 0%), and pleural effusions (77.8% vs 0%). Conclusions: Major overlaps of lung CT imaging features existed between COVID-19 pneumonia and acute HF cases. However, signs of fluid redistribution are clues that favour HF over COVID-19 pneumonia.
HYPOTHESIS | doi:10.20944/preprints202003.0435.v1
Subject: Medicine & Pharmacology, Other Keywords: coronavirus; fevers; pneumonia; nutrients; sauna baths; physical exercise
Online: 29 March 2020 (11:25:23 CEST)
The recent outbreak and spread of the COVID-19 virus infection across the world has seen a massive global system-wide shutdown of human social and economic activity. Both developed and developing nations have been forced to contain and isolate their citizens as much as possible. However, the continuous rising cases in both categories of nations, especially those with poor or nonexistent testing facilities and healthcare systems pose a hidden danger. The seemingly lack of and access to a truly global concerted research effort in both temporary but effective symptom mitigation may lead to more deaths in infected cases. We propose that a fusion of both technological and home-grown solutions can be utilized effectively to manage symptoms. This would add to the preventive methods of social distancing, isolation, quarantine and frequent handwashing to halt the impact of the disease. We also hope to spur further research in such drug/non-drug combination therapy-based methods with emphasis on effectiveness based on quality of nutrient sources.
ARTICLE | doi:10.20944/preprints202002.0220.v2
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: coronavirus; COVID-19 pneumonia; pathology; SARS-CoV-2
Online: 2 March 2020 (01:34:58 CET)
There is currently a lack of pathologic data on the novel coronavirus (SARS-CoV-2) pneumonia, or COVID-19, from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of surgery. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that, apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Since both patients did not exhibit symptoms of pneumonia at the time of surgery, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.
Subject: Medicine & Pharmacology, Allergology Keywords: Coronavirus; SARS-CoV-2; COVID-19; Thalidomide; pneumonia
Online: 26 February 2020 (12:31:47 CET)
A novel coronavirus strain (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first appeared in December 2019 and can cause acute respiratory distress syndrome and death. However, there are only limited therapy choices and no vaccine for SARS-CoV-2 is currently available. Here we report about a case of a SARS-CoV-2 caused pneumonia successfully treated with thalidomide. Thalidomide is an immunomodulatory and anti-inflammatory agent and was combined with a low-dose glucocorticoid. We suggest, that the effects of thalidomide might be related to regulating immunity, inhibiting the inflammatory cytokine surge, alleviating anxiety to reduce oxygen consumption, relieving vomit and lung exudation.
ARTICLE | doi:10.20944/preprints202207.0149.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: clinical S.aureus; skin carriage; geriatric-MRSA pneumonia; endogenous-S.aureus
Online: 11 July 2022 (04:33:22 CEST)
The changing epidemiology of Staphylococcus aureus has created several gaps in its population structure and emergence of strains. Two global shifts in the aftermath of the past methicil-lin-resistant S. aureus (MRSA) pandemic are: a rise in healthcare-associated infections and evolu-tion of cutaneous and soft tissue infections with high morbidities and mortalities. Furthermore, bitter lessons from COVID-19 showed S. aureus necrotizing-pneumonia and skin conditions ag-gravating Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Monkeypox manifestations. Limited data and paucity of high-quality evidence exist for many key clinical questions. Using clinical microbiology, molecular characterization, hospital data on age and in-fection sites, and antibiograms, we have investigated S. aureus infection patterns. We showed that age-specific distribution in both intensive care unit (ICU) and non-ICU revealed highest infection rates (94.7%) in senior-patients >50 years; most were MRSA (81.99%). However, specific distribu-tions of geriatric MRSA and MSSA rates were 46.5% and 4.6% in ICU and 35.48% and 8.065% in non-ICU, respectively. Intriguingly, age groups 0-20 years showed uniquely similar MRSA pat-terns in ICU and non-ICU patients (13.9%, 9.7%, respectively) and MSSA in ICU (11.6%). In age groups 20-50 years, MRSA were 2-fold in non-ICU (35%) than ICU (18.6%). Interestingly, highly significant association was found between infection-site and age-groups (P-value .000). Skin in-fections remained higher in all ages; pediatrics 32.14%, adults 56%, and seniors 25% while res-piratory infections were lower in pediatrics (14.3%) and adult 17%), and highest in seniors (38%). Blood and “other” sites in pediatrics recorded (28.6%; 25%, respectively), slightly lower in adults (18.6%; 8.6%) and seniors (14%); 22.8%), respectively. Further, significant association existed between infection-site and MRSA (Chi-Square Test, P-value .002). The common cutaneous infec-tions across all age-groups and the significant association of MRSA to geriatric-respiratory infec-tions have a high potential for skin-carriage as reservoir for endogenous infection. The similar frequencies of both lineages in youth in all settings imply MSSA-carriage as potential evolutionary origins for MRSA. These findings have important clinical implications for strategic planning in patient management and S. aureus control particularly in age-specific infections and vigilance for potential viral coinfections.
BRIEF REPORT | doi:10.20944/preprints202009.0229.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; pneumonia; low-dose whole-lung irradiation; SpO2
Online: 10 September 2020 (08:36:57 CEST)
Purpose: Novel coronavirus disease (COVID-19) is the current global concern. Radiotherapy (RT), commonly employed in cancer management, has been considered one of the potential treatments for COVID-19 pneumonia. Here, we present the final report of the pilot trial evaluating the efficacy and safety of low-dose whole-lung irradiation (LD-WLI) in patients with COVID-19 pneumonia. Methods and Materials: We enrolled patients with moderate COVID-19 pneumonia who were older than 60 years. Participants were treated with LD-WLI in a single fraction of 0.5 or 1.0Gy along with the national protocol of COVID-19. The primary endpoints were improvement of SpO2, the number of hospital/ICU stay days, and the number of intubations after RT and the secondary endpoints were alterations of the c-reactive peptide, interleukin-6, ferritin, procalcitonin, and D-dimer. The response rate (RR) was defined as a rise in SpO2 upon RT with rising or constant trend in the next two days, and clinical recovery (CR) included patients who were discharged from the hospital or acquired SpO2 ≥93% on room air. Results: Between 21 May 2020 and 2 July 2020, ten patients were enrolled. The median age was 75 years, 80% were male, and 80% had comorbidities. The first five patients received a single 0.5Gy-WLI, and others received 1.0Gy. Patients were followed for 2-14 days (median 5.5 days). Following one day, nine patients experienced an improvement in SpO2. Five patients were discharged (median 6th day, range 2nd-14th day), and four patients died (median 7th day, range 3rd-10th day). Overall, the RR and CR were 60.0% and 55.5%, respectively. The RR and CR rates of 0.5- and 1.0Gy group were 80% vs 40% and 75% vs 40%, respectively. No acute radiation-induced toxicity was recorded. Conclusions: LD-WLI with a single 0.5Gy fraction seems to be a more appropriate dose to warrant further evaluation in a large-scale, randomized trial.
ARTICLE | doi:10.20944/preprints202007.0749.v1
Subject: Life Sciences, Virology Keywords: Bovine coronavirus; intersititial pneumonia; phylogenetic analysis; Real time PCR
Online: 31 July 2020 (13:46:21 CEST)
An outbreak of winter disease, complicated by severe respiratory syndrome, occurred in January 2020 in a high production dairy cow herd located in a hilly area of the Calabria region. Of the 52 animals belonging to the farm, 5 (9.6%) died with severe respiratory distress, death occurring 3-4 days after the appearance of the respiratory signs (caught and gasping breath). Microbiological analysis revealed absence of pathogenic bacteria whilst Real-time PCR identified the presence of RNA from Bovine Coronavirus (BCoV) in several organs: lungs, small intestine (jejunum), mediastinal lymph nodes, liver and placenta. Since being the only pathogen identified, BCoV was hypothesized to be the cause of the lethal pulmonary infection. Like the other CoVs, BCoV is able to cause different syndromes. Its role in calfhood diarrhoea and in mild respiratory disease is well known: we report instead the involvement of this virus in a severe and fatal respiratory disorder, with symptoms and disease evolution resembling that of Severe Acute Respiratory Syndromes (SARS).
REVIEW | doi:10.20944/preprints202004.0091.v1
Subject: Life Sciences, Virology Keywords: Coronavirus; Pneumonia; COVID-19; Virus; Flu; Vaccine; Epidemic; Pandemic
Online: 7 April 2020 (11:15:55 CEST)
The SARS-CoV-2 is a recently identified positive sense single stranded RNA virus and member of the coronavirus family of viruses. It is thought to be the etiological factor for the ongoing COVID-19 pandemic. This virus is thought to have originated from bats and acquired ability of human-to-human transmission. While SARS-CoV-2 is relatively benign, it has infected more than half a million people (as of March 29th 2020) worldwide and the number of infected people continues to rise. More than 170 countries have reported COVID-19 positive cases. With a mortality rate of less than both the previous coronavirus outbreaks, COVID-19 has (conversely) caused the death of over 33,980 (as of 29th March, 2020 at 22.00 hours EDT) people worldwide and the number is increasing. Given the enormous impact of this virus on human health and wellbeing and consequent devastating impacts on world trade, economics and quality of life, it is important to understand this virus better and get insight into its pathogenic mechanisms which will aid in devising effective measure to curb its spread and predict future pattern of its interaction with humans. Though very little is known about this SARS-CoV-2 but its mechanisms and patterns of spread can be speculated (with caution, nevertheless) from what we know about its closest relatives SARS-CoV-1 (responsible for SARS-2002 epidemic) and MERS-CoV (responsible for MERS-2012 epidemic). In the present review, we aim at bringing together the coherent and peer reviewed literature about the SARS-CoV-2 and its close relatives and try to understand its infection patterns and reconstruct its pathogenic mechanisms with anecdotes on diagnosis and future directions. We hope that this paper will serve the purpose of being a reliable source of information to scientists, clinicians and general public.
REVIEW | doi:10.20944/preprints202006.0157.v1
Subject: Keywords: novel coronavirus; SARS-CoV-2; COVID-19; pneumonia; Betacoronavirus; transmission
Online: 14 June 2020 (03:06:15 CEST)
The emergence of novel coronavirus (SARS-CoV-2) in marked as the highest pathogenic coronavirus that has crossed from the hosts to the human population in the twenty-first century. The spreading of COVID-19 in different chinese cities and around the world is travel-related viral spread with the unprecedented nosocomial outbreaks. It has also shown with high case-fatality rates, indeed to urgent prophylactic and therapeutic settings. Scientific advancements of the SARS-CoV-2 pandemic allowed for rapid progress to understand the epidemiology and pathogenesis of SARS-CoV-2. This review highlights the the genomic structure of SARS-CoV-2 with the proposed roles of genotype and phenotype of SARS-CoV-2 in pathogenesis and discuss recent results supporting treatment strategies of COVID-19 with a special focus on how these new insights may facilitate rational development of SARS-CoV-2 for targeted therapies in the future.
HYPOTHESIS | doi:10.20944/preprints202002.0254.v2
Subject: Medicine & Pharmacology, Other Keywords: 2019-nCoV; novel coronavirus pneumonia; docking; ACE2; viral main protease
Online: 23 February 2020 (02:09:52 CET)
The 2019 novel coronavirus (2019-nCoV) causes novel coronavirus pneumonia (NCP). Given that approved drug repurposing becomes a common strategy to quickly find antiviral treatments, a collection of FDA-approved drugs can be powerful resources for new anti-NCP indication discoveries. In addition to synthetic compounds, Chinese Patent Drugs (CPD), also play a key role in the treatment of virus related infections diseases in China. Here we compiled major components from 38 CPDs that are commonly used in the respiratory diseases and docked them against two drug targets, ACE2 receptor and viral main protease. According to our docking screening, 10 antiviral components, including hesperidin, saikosaponin A, rutin, corosolic acid, verbascoside, baicalin, glycyrrhizin, mulberroside A, cynaroside, and bilirubin, can directly bind to both host cell target ACE2 receptor and viral target main protease. In combination of the docking results, the natural abundance of the substances, and botanical knowledge, we proposed that artemisinin, rutin, glycyrrhizin, cholic acid, hyodeoxycholic acid, puerarin, oleanic acid, andrographolide, matrine, codeine, morphine, chlorogenic acid, and baicalin (or Yinhuang Injection containing chlorogenic acid and baicalin) might be of value for clinical trials during a 2019-nCov outbreak.
ARTICLE | doi:10.20944/preprints202203.0272.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Ozone; Ozone therapy; pneumonia; COVID-19; SARS-CoV-2; rectal insufflation
Online: 19 March 2022 (03:35:45 CET)
Objective: To evaluate the effect of rectal Ozone (O3) in severe COVID-19 pneumonia in two different cohorts differing in location (Madrid vs Zilina), ethnicity (Slovakian vs Spanish cohorts) and age. Material and Methods: In a multicenter-study, 32 severe bilateral-COVID-19-pneumonia patients and (+) RT-PCR (reverse transcriptase polymerase chain reaction) SARS-CoV-2 were evaluated (16 from each cohort). Primary outcomes: a) clinical (O2-saturation); b) biochemical (Lymphocyte-count, Fibrinogen, D-Dimer, Urea, Ferritin, LDH [lactate dehydrigenase], IL-6 and CRP [c-reactive protein]); and c) radiological improvement. Secondary outcomes: a) days-of-hospitalization, b) mortality-rate before discharge. The Ozone-protocol consisted of 10 sessions of intra-rectal Ozone, total dose 5.25 mg (150 mL volume, 35 g/ml concentration). The Standard-of-care protocol included O2 supply, antivirals (Remdesivir / Isoprinosine), corticosteroids (Dexamethasone / Metilprednisolone), monoclonal antibodies (Anakinra / Tocilizumab), antibiotics (Azytromicine), anticoagulants (Enoxaparine / Fraxiparine). Protocol was approved by Health Care Ethics Committee (Report 15/4/2020) of our Hospital and by Ethics Committee for Medical Investigation of La Princesa’s Hospital (ACTA CEIm 12/20, 28/5/20, Registry 4146). Results: Patients in Slovakian cohort were younger (53.38 vs 84.69 years). Grade of severity was worse in Spanish-cohort (4.78 vs 3.30 points). Length of stay was superior in Spanish-cohort (27.38 vs 10.07 days). Both cohorts improved O2-saturation and Lymphocyte-count. Inflammation biomarkers (Fibrinogen, D-Dimer, Urea, Ferritin, LDH, CRP and IL-6) decreased in both cohorts. In Spanish-cohort, Urea and Ferritin improvement was not significant (p>0.05), while in Slovakian-cohort, Urea, Fibrinogen and LDH were not significant (p>0.05) Radiological signs of bilateral pneumonitis decreased on both cohorts. Mortality was similar (12.5%). Conclusion: After Standard of care protocol, Rectal Ozone improved O2-saturation, decreased inflammation biomarkers and improved Taylor’s radiological scale in both cohorts. Although age, grade of severity and days of hospitalization were inferior in Slovakian cohort, mortality was similar in both cohorts, but inferior if compared to an external control cohort.
CASE REPORT | doi:10.20944/preprints202009.0544.v2
Subject: Medicine & Pharmacology, Allergology Keywords: Systemic lupus erythematosus (SLE); Intravenous immunoglobulins (IVIG); Autoantibody; Autoimmune disease; Pneumonia
Online: 23 April 2021 (09:48:40 CEST)
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a broad array of clinical signs. In this study, we aimed to use intravenous immunoglobulins (IVIG), called intacglobin, as a monotherapy to manage SLE in three patients. Laboratory investigations for SLE diagnosis were performed, including the detection of anti-nuclear antibodies (ANA) and SLE confirmation by detecting high titers of anti-dsDNA antibodies. C3 and C4 serum levels were assessed, as well as the determination of immunoglobulins. The SLEDAI score was measured to determine whether a significant degree of disease activity existed and as a prognostic value. The evaluation of any chest infection was performed by chest-X-ray. The patients were treated with five–ten g/day of IVIG for six consecutive days, followed by five–ten g/month. Immunological evaluation demonstrated that patients presented with a flare of SLE with high titers of ANA and anti-dsDNA antibodies, low C3 and C4, and elevated immunoglobulin levels. The SLEDAI score falls from 10 to below 3, and chest infections in some patients are cleared up. The postulated mechanisms of action of IVIG demonstrated that it could be used as an immunosuppressor, immunomodulator, and antimicrobial agent in patients with SLE.
REVIEW | doi:10.20944/preprints202101.0297.v1
Subject: Materials Science, Biomaterials Keywords: COVID-19; SARS-CoV-2; carbon-based nanomaterials; antiviral properties; pneumonia
Online: 15 January 2021 (13:30:21 CET)
Therapeutic options for the highly pathogenic human Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) causing the current pandemic Coronavirus disease (COVID-19) are urgently needed. COVID-19 is associated with viral pneumonia and acute respiratory distress syndrome causing significant morbidity and mortality. The proposed treatments for COVID-19, such as hydroxychloroquine, remdesivir and lopinavir/ritonavir, have shown little or no effect in the clinic. Additionally, bacterial and fungal pathogens contribute to the SARS-CoV-2 mediated pneumonia disease complex. The antibiotic resistance in pneumonia treatment is increasing at an alarming rate. Therefore, carbon-based nanomaterials (CBNs), such as fullerene, carbon dots, graphene, and their derivatives constitute a promising alternative due to their wide-spectrum antimicrobial activity, biocompatibility, biodegradability and capacity to induce tissue regeneration. Furthermore, the antimicrobial mode of action is mainly physical (e.g. membrane distortion), which is characterized by a low risk of antimicrobial resistance. In this review, we evaluated the literature on the antiviral activity and broad-spectrum antimicrobial properties of CBNs. CBNs had antiviral activity against 12 enveloped positive-sense single-stranded RNA viruses similar to SARS-CoV-2. CBNs with low or no toxicity to the humans are promising therapeutics against COVID-19 pneumonia complex with other viruses, bacteria and fungi, including those that are multidrug-resistant.
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.
ARTICLE | doi:10.20944/preprints202007.0342.v1
Subject: Keywords: Propolis; Soxhlet; Anthraquinone; antibacterial activity; Proteus Mirabilis; Klebsiella Pneumonia; Staphylococcus Qureus
Online: 16 July 2020 (06:19:30 CEST)
Different products from a unique Propolis extract, Propolis (bee glue), an of resinous consistency produced by bees, has been used as indigenous medicine for the treatment of several diseases in some contrary. Safety assessment of propoils extracts with respect to antimicrobial activity against three bacterial isolates, Proteus Mirabilis , Klebsiella Pneumonia and Staphylococcus Qureus.The result showed that the main composition of the extract was Anthraquinone, the last one was responsible for the biological activity of the extract. FT-IR, UV results showed more than eight peaks for represent the main fine composition of the extract. The present study also showed that the extract has antibacterial activity against three bacterial isolates
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: ozone therapy; ozonized saline solution; SARS-CoV-2; COVID-19; pneumonia
Online: 12 July 2020 (16:30:51 CEST)
Currently, there is no effective antiviral therapy recommended for the new coronavirus disease 2019 pneumonia (COVID-19). The purpose of this pilot study was to evaluate the safety of Ozonized Saline Solution (O3SS) used as a complementary therapy in adult patients COVID-19. Twenty-five adult patients who were hospitalized with mild to severe COVID-19 symptoms, who met the inclusion criteria and were being treated from April 18rd to April 26th, 2020, at the Viamed Virgen De La Paloma Hospital, Madrid, Spain were included in this study. Patients were allocated to receive standard care (SC) that included 200-400 mg hydroxychloroquine twice daily for 5-7 days plus Tocilizumab 400 mg twice daily for 5 days, low molecular weight heparin (LMWH) and 40 mg-60 mg metil-prednisone plus O3SS, 200 mL, 3-5 µg/mL daily for 10 days. No control group was included, data were compared to clinical trials in this subject. Primary outcomes of treatment with O3SS were an improvement of clinical symptoms and a reduction in mortality. Secondary end points evaluated included participant clinical status, laboratory examinations, and duration of viral shedding. None of the patients treated with SC + O3SS died. Improvements in symptoms such as dyspnea, weakness, and reduction in body temperature were observed and corresponded with an improvement of laboratory finding including D-dimer, fibrinogen, LDH, and CRP. No side effects from the O3SS treatment were observed. Conclusions: COVID-19 patients with mild to severe symptoms who received intravenous O3SS as a complementary therapy demonstrated no side effects. This preliminary data will be served as base for a future study of the efficacy of this therapy.
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: Novel coronavirus pneumonia; COVID-19; SARS-CoV-2; Pathology; Critical patient
Online: 9 March 2020 (10:31:10 CET)
Background Critical patients with novel coronavirus pneumonia ( COVID-19) have worse outcome and high mortality. However, the histopathology of critical patient with COVID-19 remains undisclosed. Methods We performed the whole lung biopsy, and described the pathological changes of critical COVID-19 patient done with transplant by HE staining, immunohistochemistry and special staining observed under the microscopy. Findings The whole lungs displayed diffuse congestive appearance and partly haemorrhagic necrosis on gross examination. The haemorrhagic necrosis was prominently present in outer edge of the right lower lung. The cut surfaces of the lung displayed severe congestive and haemorrhagic changes. The main pathological changes showed massive pulmonary interstitial fibrosis, and partly hyaline degeneration, variable degrees of hemorrhagic pulmonary infarction. Small vessels hyperplasia, vessel wall thickening, lumen stenosis, occlusion and microthrombosis formation. Focal monocytes, lymphocytes and plasma cells infiltrating into pulmonary interstitium. Bronchiolitis and alveolitis with proliferation, atrophy, desquamation and squamous metaplasia of epithelial cells. Atrophy, vacuolar degeneration, proliferation, desquamation and squamous metaplasia in alveolar epithelial cells. Alveolar cavity congestion was prominent, and contained mucus, edema fluid, desquamated epithelial cells, and inflammatory cells. We also found several multinucleate giant cells and intracytoplasmic viral inclusion bodies. Special stains including Masson stain, sirius red staining, reticular fibers staining indicated massive pulmonary interstitial fibrosis. Immunohistochemistry showed positive for immunity cells including CD3, CD4, CD8, CD20, CD79a, CD5, CD38 and CD68. Interpretation We demonstrate the pathological findings of critical patient with COVID-19, which might provide a deep insight of the pathogenesis and severity of this disease.
ARTICLE | doi:10.20944/preprints201904.0070.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: mycoplasma pneumoniae pneumonia; macrolide antibiotics; antibiotic resistance; corticosteroids; prednisolone; methylprednisolone; children
Online: 7 April 2019 (12:35:26 CEST)
Antibiotics’ effect on Mycoplasma pneumoniae (MP) infection still remains controversial. A prospective study of 257 children with MP pneumonia during a recent epidemic (2015-2016) was conducted. All MP pneumonia patients were treated with corticosteroids within 24-36 h after admission. Initially, oral prednisolone (1 mg/kg) or intravenous methylprednisolone (IVMP) (1-2 mg/kg) was administered for mild pneumonia patients, and IVMP (5 -10 mg/kg/day) for severe pneumonia patients. If patients showed persistent fever for 36-48 hours or disease progression, additive IVMP (5 mg/kg or 10 mg/kg) was given. Eighty-five patients received only a broad-spectrum antibiotic without macrolide. The mean age and the male:female ratio were 5.6 ± 3.1 years, respectively. Seventy-four percent of patients (190/257) showed immediate defervescence within 24 h, and 95.7% (246/257) of patients showed defervescence within 72 h with improvements in clinical symptoms. Eight patients who received additive IVMP also showed clinical improvement within 48 h without adverse reactions. There were no clinical or laboratory differences between patients treated with a macrolide (n = 172) and without (n = 85). Early corticosteroid therapy might reduce disease morbidity and prevent disease progression in MP pneumonia patients without side effects, and antibiotics may have limited effects on MP infection.
Subject: Biology, Other Keywords: SARS-CoV-2; RATG13; BtCoV/4991; SARS-like (SL-) corona virus; pneumonia
Online: 24 May 2020 (20:02:22 CEST)
Genomic analysis indicates that SARS-CoV-2 is most related to RaTG13, a beta corona virus derived from bats by 96% 1. At present, RaTG13 is only available on the public database in the form of a genome sequence. The genome of RaTG13 (MN996532.1) was sequenced from the RNA of a bat faecal swab collected in 2013 from Yunnan, China, however the exact location is not mentioned. Since RaTG13 is one of the main supports for SARS-CoV-2 to have a natural origin, it is of utmost importance to understand the sample location. RNA dependent RNA polymerase (RdRp) sequence of RaTG13 shows that it is 100% similar to that of bat corona virus BtCoV/4991 and 98.7-98.9% similar to SARS-CoV-2 RdRp 2. BtCoV/4991 was described to be a SARS-like (SL-) corona virus from bat faeces sampled in an abandoned mine from Mojiang 2. Both the publications 1,2 are authored by Dr. Zheng-li Shi (Z-L Shi), who is described as the bat woman of China 3. However, BtCoV/4991 has not been mentioned by Zhou et al 2020 1 where novel corona virus was first described. Based on the RdRp sequence similarities, similarities in sample collection dates, sample locations, and the fact that RaTG13 is mentioned synonymous to BtCoV/4991 on the Chinese bat database, it is predicted that RaTG13 and BtCoV/4991 originate from the same sample. The sample, bat faecal swab was collected in 2013 from an abandoned mineshaft in Mojiang by Dr. Shi and her work group. In 2012, in a Mojiang mineshaft, six mine workers suffered from atypical pneumonia and three of them died. These workers were engaged in the work of clearing debris from a mineshaft which had a lot of bats and bat faeces 3,4. A detailed health investigation indicated that the miners suffered from atypical pneumonia mostly of the viral origin 4. Therefore, in the light of the present Covid-19 caused by SARS-CoV-2, the fact that its phylogenetic neighbour RaTG13 originated from bat faeces collected from a mineshaft, which was also the origin of pneumonia-like disease in miners in 2012, should be noted.
Subject: Medicine & Pharmacology, Allergology Keywords: antibodies; COVID-19; glycans; immunoglobulin M; SARS-CoV-2; pneumonia; prediction; protection
Online: 24 April 2020 (10:25:27 CEST)
The natural history of COVID-19 caused by SARS-CoV-2 is extremely variable, ranging from asymptomatic infection, to pneumonia, and to complications eventually fatal. We propose here the first model, explaining how the outcome of first, crucial 10-15 days after infection, hangs on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, MBL). If SARS-CoV-2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm) leading to complications often requiring intensive therapy and being, in some patients, fatal. Strenuous exercise and high flow air in the incubation days and early stages of COVID-19, facilitates direct penetration of the virus to the lower airways and the alveoli, without impacting on the airway’s mucosae covered by neutralizing antibodies. This allows the virus to bypass the efficient immune barrier of the upper airways mucosa in young and healthy athletes. In conclusion, whether the virus or the adaptative immune response reach the lungs first, is a crucial factor deciding the fate of the patient. This “quantitative and time-sequence dependent” model has several implications for prevention, diagnosis, and therapy of COVID-19.
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.
ARTICLE | doi:10.20944/preprints202007.0591.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: Bacterial -Viral Pneumonia; COVID-19; X-ray Image; Deep Learning; Convolution Neural Network
Online: 24 July 2020 (14:02:07 CEST)
The paper demonstrates the analysis of Corona Virus Disease based on a CNN probabilistic model. It involves a technique for classification and prediction by recognizing typical and diagnostically most important CT images features relating to Corona Virus. The main contributions of the research include predicting the probability of recurrences in no recurrence (first time detection) cases at applying our proposed Convolution neural network structure. The Study is validated on 2002 chest X-ray images with 60 confirmed positive covid19 cases and (650 bacterial – 412 viral -880 normal) x-ray images. The proposed CNN compared with traditional classifiers with proposed CHFS feature extraction model. The experimental study has done with real data demonstrates the feasibility and potential of the proposed approach for the said cause. The result of proposed CNN structure has been successfully done to achieve 98.20% accuracy of covid19 potential cases with comparable of traditional classifiers.
CASE REPORT | doi:10.20944/preprints202007.0219.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: Preterm infant; Necrotizing pneumonia; Methicillin-Resistant Staphylococcus Aureus (MRSA); Pneumatoceles; Linezolid; Vancomycin; Rifampicin
Online: 11 July 2020 (02:10:45 CEST)
Necrotizing pneumonia due to Methicillin-Resistant Staphylococcus Aureus (MRSA) is devastating and difficult to treat in preterm infants. We report a case of severe MRSA necrotizing pneumonia in a preterm infant. As an add-on rescue therapy to vancomycin, linezolid rapidly cured this case after the failure of vancomycin plus rifampicin. This rapid cure suggests that adjunctive rather than rescue linezolid may be considered in such cases.
ARTICLE | doi:10.20944/preprints202002.0171.v1
Subject: Life Sciences, Microbiology Keywords: Lysophosphatidylcholine; combined antimicrobial treatment; immune response; peritoneal sepsis model; pneumonia model; Pseudomonas aeruginosa
Online: 13 February 2020 (12:48:49 CET)
Immune response stimulation may be an adjuvant to antimicrobial treatment. Here, we evaluated the impact of immune response modification by lysophosphatidylcholine (LPC) combined with imipenem or ceftazidime in murine models of peritoneal sepsis (PS) and pneumonia by Pseudomonas aeruginosa. Imipenem and ceftazidime-susceptible strain (Pa39), and imipenem and ceftazidime-resistant strain (Pa238) were used. Ceftazidime pharmacokinetic and pharmacodynamic parameters were determined. Therapeutic efficacy, and TNF-α and IL-10 levels were determined in murine models of PS and pneumonia by Pa39 and Pa238 treated with LPC, imipenem or ceftazidime, alone or in combination. In PS model, LPC+ceftazidime reduced spleen and lungs Pa238 concentrations (-3.45 and -3.56 log10 CFU/g; P<0.05) than ceftazidime monotherapy, while LPC+imipenem maintained the imipenem efficacy (-1.66 and -1.45 log10 CFU/g; P>0.05). In pneumonia model, LPC+ceftazidime or LPC+imipenem reduced lungs Pa238 concentrations (-2.37 log10 CFU/g, P=0.1, or -1.35 log10 CFU/g, P=0.75). For Pa39 no statistically significant difference has been observed in PS and pneumonia models between combined therapy and monotherapy. Moreover, LPC+imipenem and LPC+ceftazidime decreased and increased significantly TNF-α and IL-10 levels, respectively, in comparison with untreated controls and monotherapies. These results demonstrate the impact of immune response modification by LPC plus antibiotics on the prognosis of infections by ceftazidime-resistant P. aeruginosa.
REVIEW | doi:10.20944/preprints202010.0407.v2
Subject: Medicine & Pharmacology, Allergology Keywords: COVID-19; SARS-CoV-2; coronavirus; vitamin C; ascorbate; colds; pneumonia; sepsis; immunonutrition; supplementation
Online: 30 November 2020 (15:23:16 CET)
There are limited proven therapies for the treatment of COVID-19. Vitamin C’s antioxidant, anti-inflammatory and immunomodulating effects, make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19, supporting anti-inflammatory treatment. This literature review focuses on vitamin C deficiency in respiratory infections including COVID-19; the mechanism of action in infectious disease and adrenal function supporting the anti-inflammatory actions of glucocorticosteroids: its role in preventing and treating colds and pneumonia and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8g/d) may reduce incidence and duration of respiratory infections and intravenous vitamin C (2-24g/d) has been shown to reduce mortality, Intensive Care Unit and hospital stays, time on mechanical ventilation in severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and frequency of vitamin C deficiency in respiratory infections it may be worthwhile testing patients’ vitamin C status and treating accordingly with intravenous use within ICUs and orally with doses between 2 and 8g/day in hospitalised and infected persons.
REVIEW | doi:10.20944/preprints202008.0366.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: vaccine; age; pneumonia; influenza virus; seasonal influenza; influenza imprinting; infant; infant immunity; immune response
Online: 17 August 2020 (12:04:58 CEST)
Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system is thought to synergistically play a role in the increased disease severity in younger age groups. Although vaccines remain the best solution for protecting this vulnerable population, no vaccines are available for those under 6 months, and for infants aged 6 months to 2 years, the vaccine elicits a dampened immune response. Dampened immune responses may be due to unique features of the infant immune system and a lack of pre-existing immunity. Unlike older children and adults, the infant immune system is Th2 skewed and has less antigen presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. To provide better protection against influenza virus infection and disease in infants, more research must be conducted to understand the imprinting event. We contend that by understanding influenza imprinting in the context of the infant immune system and the infant’s immature respiratory tract, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets, which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune development, current vaccine strategies, respiratory development, and the importance of researching the imprinting event in infant animal models to develop more effective and protective vaccines for young children.
REVIEW | doi:10.20944/preprints201709.0163.v1
Subject: Medicine & Pharmacology, Other Keywords: next-generation sequencing; whole-genome sequencing; hospital-acquired pneumonia; antibiotic resistance; prediction; clinical metagenomics
Online: 30 September 2017 (04:49:23 CEST)
Clinical metagenomics (CMg), referred to as the application of next-generation sequencing (NGS) to clinical samples, is a promising tool for the diagnosis of hospital-acquired pneumonia (HAP). Indeed, CMg allows identifying pathogens and antibiotic resistance genes (ARGs), thereby providing the information required for the optimization of the antibiotic regimen. Hence, provided that CMg would be faster than conventional culture, the probabilistic regimen used in HAP could be tailored faster, which should lead to an expected decrease of mortality and morbidity. While the inference of the antibiotic susceptibility testing from metagenomic or even genomic data is challenging, a limited number of antibiotics are used in the probabilistic regimen of HAP (namely beta-lactams, aminoglycosides, fluoroquinolones, glycopeptides and oxazolidinones). Accordingly in the perspective of applying CMg to the early diagnostic of HAP, we aimed at reviewing the performances of whole genomic sequencing (WGS) of the main HAP-causing bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus) for the prediction of susceptibility to the antibiotic families advocated in the probabilistic regimen of HAP.
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.
ARTICLE | doi:10.20944/preprints202105.0605.v1
Subject: Mathematics & Computer Science, Algebra & Number Theory Keywords: deep learning; computed tomography; image classification; COVID-19; medical image analysis; pneumonia; CNN, LSTM, medical diagnosis
Online: 25 May 2021 (10:32:29 CEST)
Advancements in deep learning and availability of medical imaging data have led to use of CNN based architectures in disease diagnostic assisted systems. In spite of the abundant use of reverse transcription-polymerase chain reaction (RT-PCR) based tests in COVID-19 diagnosis, CT images offer an applicable supplement with its high sensitivity rates. Here, we study classification of COVID-19 pneumonia (CP) and non-COVID-19 pneumonia (NCP) in chest CT scans using efficient deep learning methods to be readily implemented by any hospital. We report our deep network framework design that encompasses Convolutional Neural Networks (CNNs) and bidirectional Long Short Term Memory (biLSTM) architectures. Our study achieved high specificity (CP: 98.3%, NCP: 96.2% Healthy: 89.3%) and high sensitivity (CP: 84.0%, NCP: 93.9% Healthy: 94.9%) in classifying COVID-19 pneumonia, non-COVID-19 pneumonia and healthy patients. Next, we provide visual explanations for the CNN predictions with gradient-weighted class activation mapping (Grad-CAM). The results provided a model explainability by showing that Ground Glass Opacities (GGO), indicators of COVID-19 pneumonia disease, were captured by our CNN network. Finally, we have implemented our approach in three hospitals proving its compatibility and efficiency.
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: automatic detection; chest X-ray; convolutional neural network; COVID-19; deep learning; feature extraction; image classification; pneumonia
Online: 27 April 2021 (14:08:53 CEST)
One of the critical tools for early detection and subsequent evaluation of the incidence of lung diseases is chest radiography. At a time when the speed and reliability of results, especially for COVID-19 positive patients, is important, the development of applications that would facilitate the work of untrained staff involved in the evaluation is also crucial. Our model takes the form of a simple and intuitive application, into which you only need to upload X-rays: tens or hundreds at once. In just a few seconds, the physician will determine the patient's diagnosis, including the percentage accuracy of the estimate. While the original idea was a mere binary classifier that could tell if a patient was suffering from pneumonia or not, in this paper we present a model that distinguishes between a bacterial disease, a viral infection, or a finding caused by COVID-19. The aim of this research is to demonstrate whether pneumonia can be detected or even spatially localized using a uniform, supervised classification.
REVIEW | doi:10.20944/preprints202005.0085.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: COVID-19; HAPE; high-altitude; tolerance to hypoxia; oxygen transport triad; Cov-2; SARS; pneumonia; ventilators; EPO
Online: 5 May 2020 (15:26:05 CEST)
The critical hypoxia in COVID-19 patients during this pandemic, has taken away many lives all around the globe. The mechanism has been poorly understood and initially, word got around that it was a SARS (Severe Acute Respiratory Syndrome) pneumonia. The atypical images in lung computerized axial tomography (CAT) scans were alarming. This immediately alerted everyone including poor countries to purchase lacking sophisticated ventilator equipment. However, in some countries, even 88% of the patients on ventilators lost their lives. New observations and pathological findings are gradually clarifying the disease. What seems evident is that it is not only one disease but several, with different responses in different countries and different altitudes. The critical hypoxia and «gasping» present in some patients are not totally understood. It was mentioned that it could be like a High-Altitude Pulmonary Edema (HAPE). Hereby, as high-altitude medicine and hypoxia physiology specialists, we compare the pathophysiology with that of high-altitude exposure in order to understand the mechanisms involved. Some differences in lung radiological images along with transmission and viral attack mechanisms are discussed. The oxygen transport triad used at high-altitude can be applied on this pathology in order to propose even the use of erythropoietin (EPO) early in the treatment. The immune system is the most important long-term survival tool, so we suggest a short-term strategy: the use of special Earth open-circuit astronaut-resembling suits with effective outside air filtering re-breathing mechanisms in order to return to work and daily activities, without contamination risk. Thereby, the curve can be flattened without quarantine and the economy could recover.
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.
ARTICLE | doi:10.20944/preprints202009.0647.v1
Subject: Mathematics & Computer Science, Algebra & Number Theory Keywords: Lung condition; COVID-19; Machine learning; Custom Vision; Core ML; Auto ML; AI; Pneumonia; Smartphone application; Real-time diagnosis
Online: 26 September 2020 (16:14:39 CEST)
AI is leveraging all aspects of life. Medical services are not untouched. Especially in the field of medical image processing and diagnosis. Big IT and Biotechnology companies are investing millions of dollars in medical and AI research. The recent outbreak of SARS COV-2 gave us a unique opportunity to study for a non interventional and sustainable AI solution. Lung disease remains a major healthcare challenge with high morbidity and mortality worldwide. The predominant lung disease was lung cancer. Until recently, the world has witnessed the global pandemic of COVID19, the Novel coronavirus outbreak. We have experienced how viral infection of lung and heart claimed thousands of lives worldwide. With the unprecedented advancement of Artificial Intelligence in recent years, Machine learning can be used to easily detect and classify medical imagery. It is much faster and most of the time more accurate than human radiologists. Once implemented, it is more cost-effective and time-saving. In our study, we evaluated the efficacy of Microsoft Cognitive Service to detect and classify COVID19 induced pneumonia from other Viral/Bacterial pneumonia based on X-Ray and CT images. We wanted to assess the implication and accuracy of the Automated ML-based Rapid Application Development (RAD) environment in the field of Medical Image diagnosis. This study will better equip us to respond with an ML-based diagnostic Decision Support System(DSS) for a Pandemic situation like COVID19. After optimization, the trained network achieved 96.8% Average Precision which was implemented as a Web Application for consumption. However, the same trained network did not perform like Web Application when ported to Smartphone for Real-time inference, which was our main interest of study. The authors believe, there is scope for further study on this issue. One of the main goals of this study was to develop and evaluate the performance of AI-powered Smartphone-based Real-time Applications. Facilitating primary diagnostic services in less equipped and understaffed rural healthcare centers of the world with unreliable internet service.
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.