The ongoing SARS-CoV-2 pandemic has raised concerns surrounding immunological protection against the virus, particularly for people with inborn errors of immunity (IEI). While COVID-19 vaccination induces robust antibody, memory B-cell, and T-cell responses in healthy individuals, how well vaccination protects people with IEI against infection and severe disease remains unclear – especially in the context of new viral variants and vaccine formulations – leading to anxiety, ongoing self-isolation, and repeated vaccination with limited evidence of increased efficacy. Whilst most people with IEI generate some level of cellular and/or humoral immunity to COVID-19 vaccination, the level of protection and durability of the response are unclear. Alongside vaccination, antibody-based therapeutics are aimed at limiting infection and severe disease in this cohort. Immunoglobulin replacement therapy (IgRT) provides passive immunity in antibody-deficient individuals. However, to successfully prevent SARS-CoV-2 infection, a sufficient number of neutralizing antibodies must be present in product. While antibodies against circulating variants are eventually present in IgRT products (both from natural infection and vaccination of the donors), evidence of their capacity to recognize new variants is limited. Furthermore, while antibody-based pre- and post-exposure prophylaxis can be effective, they are susceptible to decreased efficacy in the context of variant evolution. This review provides an in-depth overview of current knowledge about COVID-19 vaccine efficacy in IEIs, the efficacy of SARS-CoV-2-specific antibody products, and knowledge and technological advances required for continued protection of people with IEI.

Since the outbreak of COVID-19, one of the strategies used to search for new drugs has been to find inhibitors of the main protease (Mpro) of virus SARS-CoV-2. Initially, previously reported inhibitors of related proteases like the main proteases of SARS-CoV and MERS-CoV were tested. Then a huge effort has been done by the scientific community to design, synthesize and test new small molecules acting as inactivators of SARS-CoV-2 Mpro. From the structure view, these compounds can be classified into two main groups: one corresponds to modified peptides displaying an adequate sequence for high affinity and a reactive warhead, and the second one is a diverse group including chemical compounds which do not have a peptide framework. Although a drug including a SARS-CoV-2 main protease has already been commercialized, denoting the importance of this field, more compounds have been demonstrated to be promising potent inhibitors as potential antiviral drugs.

An accurate outbreak prediction of COVID-19 can successfully help to get insight into the spread and consequences of infectious diseases. Recently, machine learning (ML) based prediction models have been successfully employed for the prediction of the disease outbreak. The present study aimed to engage an artificial neural network-integrated by grey wolf optimizer for COVID-19 outbreak predictions by employing the Global dataset. Training and testing processes have been performed by time-series data related to January 22 to September 15, 2020 and validation has been performed by time-series data related to September 16 to October 15, 2020. Results have been evaluated by employing mean absolute percentage error (MAPE) and correlation coefficient (r) values. ANN-GWO provided a MAPE of 6.23, 13.15 and 11.4% for training, testing and validating phases, respectively. According to the results, the developed model could successfully cope with the prediction task.

An outbreak of novel coronavirus(2019-nCoV) that began in Wuhan, China, is rapidly spreading to all over China, and gradually to multiple countries. Regarding to put the epidemic prevention and spread under the control, early identification and diagnosis play a critical role. Patients with initially no or mild symptoms of Novel Coronavirus Pneumonia (2019-nCoV), namely “stealth” infection, often lack of typical clinical evidence to establish the diagnosis. Based on the clinical analysis of 4 cases in stealth infection, the results of this study highlight that early diagnosis requires a combination of epidemiological history, clinical manifestations, early chest CT examination, and 2019-nCoV RNA test (nucleic acid test), with particular emphasis on definite epidemiological history and early chest CT findings when positive nucleic acid tests lag behind.

Background: Coronavirus disease 2019 (COVID-19) has emerged as a global threat to human health and disease risk increases with advancing age. The regulation of the ACE2 gene that codes for COVID-19 host receptor ACE2 has been shown to be under epigenetic regulation. Here, we examined whether intensive DNA methylation profiling of the ACE2 gene differed by human host tissue and cell type, gender, and age. Results: Accessing four public datasets, we observed unique human cell-type-specific ACE2 DNA methylation patterns. In human lung tissues, gender differences in DNA methylation at 2 sites related to the ACE2 gene were identified. Further, in freshly isolated airway epithelial cells, DNA methylation near the transcription start site of the ACE2 gene associated with biological age. Conclusion: Epigenetic profiling of host tissue may permit discovery of age and gender-related potential risk factors for COVID-19. How perturbations in ACE2 methylation relate to clinical severity across the ages and gender needs to be determined to guide screening tools and potential epigenetic modification targeting to alleviate COVID-19 morbidity in the elderly.

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.

CoVID-19 is a multi-symptomatic disease which has made a global impact due to its ability to spread rapidly, and its relatively high mortality rate. Beyond the heroic efforts to develop vaccines, which we will not discuss, the response of scientists and clinicians to this complex problem has reflected the need to detect CoVID-19 rapidly, to diagnose patients likely to show adverse symptoms, and to treat severe and critical CoVID-19. Here we aim to encapsulate these varied and sometimes conflicting approaches and the resulting data in terms of chemistry and biology. In the process we highlight emerging concepts, and potential future applications that may arise out of this immense effort.

The COVID-19 pandemic which have affected every part of the world have been deemed a public health concern and classified as a pandemic. The government imposing travel bans and quarantine measures have been found to be effective in preventing and reducing the spread of COVID-19. A reduction in physical activity and increase in the consumption of unhealthy foods have been observed to be some of the major implications of quarantine. Adequate physical activity and increased access to healthy foods would help in improving the psychological wellbeing of individuals thereby preventing the development of cardiovascular diseases.

The knowledge of COVID-19 impact on the human body has increased rapidly. Although many people recover from COVID-19, some continue to experience persistent symptoms that have been identified as Long COVID. This condition can have a severe impact on quality of life, and it remains a significant concern for medical professionals and researchers. One of the key components of the SARS-CoV-2 virus that enables it to enter human cells is the spike (S) protein. Recent studies have revealed a complex network of interactions between G proteins, spike (S) protein, and the Renin-Angiotensin System (RAS) may be responsible, at least in part, for long COVID. SARS-CoV-2 can also affect the brain, leading to neurological symptoms such as confusion, memory loss, and fatigue. Increasing evidence suggests that COVID-19 is not just a respiratory illness since it is likely that the virus could influence signal transduction pathways such as G-protein-coupled receptor (GPCR), among others, in the brain, either directly or indirectly, affecting neural functions. These interactions with the spike (S) protein and RAS, alongside the brain, are complex and require deep research to understand their implications for Long COVID-19 manifestation fully. While recent research has shed light on the complex interactions between G proteins, spike (S) protein, the brain, and the angiotensin system, this article explores these interconnected pathways and their implications for long COVID-19 manifestations. The present review summarises current research on different molecular mechanisms in Long COVID pathophysiology and may help identify possible targets or new strategies for the diagnosis and treatment.

Vaccines are crucial for controlling the COVID-19 pandemic, and booster doses are becoming increasingly important. This study aimed to assess the efficacy of the ChAdOx1 nCoV-19 vaccine from AstraZeneca as a third dose in healthcare workers at different time intervals (one, three, and six months). Two methods to measure immune response—ELISA (EUROIMMUN Medizinische Labordiagnostika AG, Luebeck, Germany) and ELISpot (Mabtech AB, Macka Strand, Sweden)—were used. A total of 170 participants were included in the study. The results showed that while IgG levels decreased at six months compared to levels at one and three months, they were still significantly higher than the baseline. Furthermore, neutralizing levels at three and six months after the third dose were not significantly different. These findings suggest that the immune response induced by the vaccine is robust and effective for several months. These results have significant implications for public health policymakers, as they provide strong support for booster vaccinations. The ChAdOx1 nCoV-19 vaccine appears to be a reliable option for preventing the spread of COVID-19, and this study provides valuable information for healthcare workers and policymakers in managing the pandemic.

Severe COVID-19 is associated with viraemia and multiple organ disease. Similar clinicopathological features have been previously seen in SARS and MERS. Clinically, the severity of SARS, MERS and COVID-19 has been associated with the presence of SARS-CoV, MERS-CoV or SARS-CoV2 viraemia in affected patients. In vitro work has looked at the pattern of viral entry and release from polarised epithelial cells infected by coronaviruses. This work has demonstrated a correlation between the severity of a coronavirus infection and the ability of the virus to reach and infect the basal surface of host cells. It has been postulated that this ability helps the virus invade the bloodstream of the host, resulting in a systemic infection with multiple organ involvement. Here we propose that basal surface release and entry of COVID-19 into and out of cells at epithelial-endothelial interface plays a key pathogenic role in severe COVID-19 disease.

Background: The question of whether children are less likely to pass on SARS-CoV-2 is important for planning society’s response to the pandemic. A document available on the Charité hospital website has not been formally published but is frequently referred to as supporting the notion that viral loads are similar in children and adults. Methods: The summary data from this document was extracted and used to produce summary statistics for three age groups: younger children (ages up to 11), older children (ages 12 to 19) and adults (ages 20 and above). Viral loads between the two children’s groups and the adult group were compared using Welch’s t test, which only requires group means and standard deviations and which is robust against moderate departures from normality. Findings: Viral loads were significantly lower than in adults for both younger children (p=0.04) and older children (p=0.04). Overall, viral loads were lower in children than adults (p=0.005). Interpretation: For both younger and older children, on average those with detectable SARS-CoV-2 have significantly lower viral loads than adults. Funding: No funding was received for this analysis.

Global differences in changes in the numbers of population-adjusted daily test-positive cases (NPDP) and deaths (NPDD) by COVID-19 were analyzed for 49 countries, including developed and developing countries. The changes as a proportion of national population were compared, adjusting by the beginning of test-positive cases increase (BPI) or deaths increase (BDI). Remarkable regional differences of more than 100 fold in NPDP and NPDD were observed. The trajectories of NPDD after BDI increased exponentially within 20 days in most countries. Machine learning analysis suggested that NPDD on 30 days after BDI was the highest in developed Western countries (1180 persons per hundred million), followed by countries in the Middle East (128), Latin America (97), and Asia (7). Furthermore, in Western countries with positive rates of the PCR test of less than 7.0%, the increase in NPDP was slowing-down two weeks after BPI, and subsequent NPDD was only 15% compared with those with higher positive rates, which suggested that the situation of testing might have affected the velocity of COVID-19 spread. The causes behind remarkable differences between regions possibly include genetic factors of inhabitants because distributions of the race and of the observed infection increasing rates were in good agreement globally.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) continues to wreak havoc threatening the public health services and imposing economic collapse worldwide. Tailoring public health responses to the SARS-CoV-2 pandemic depends on understanding the mechanism of viral replication, disease pathogenesis, and accurately identifying acute infections and mapping the spreading risk of hotspots across the globe. However, effective identification and isolation of persons with asymptomatic and mild SARS-CoV-2 infections remain the major obstacles to efforts in controlling the SARS-CoV-2 spread and hence the pandemic. Understanding the mechanism of persistent viral shedding, reinfection, and the post-acute sequalae of SARS-CoV-2 infection (PASC) is crucial in our efforts to combat the pandemic and provide better care and rehabilitation to survivors. Here we present a living literature review on SARS-CoV-2 viral persistence, reinfection and PASC. We also highlight potential areas of research to uncover putative links between viral persistence, intra-host evolution, host immune status, and protective immunity to guide and direct future basic science and clinical research priorities.

Emerging viruses description have grown at an unprecedented rate since the beginning of the 21^st century. The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its related illness, Coronavirus Disease 2019 (COVID-19) has been reported as the third highly pathogenic coronavirus introducing itself into human population in the current era after the SARS-CoV and Middle East Respiratory Syndrome (MERS-CoV). Molecular and cellular studies considering the pathogenesis of this novel coronavirus are still in the early stages of research, however, regarding the similarity of SARS-CoV-2 and other coronaviruses, it could be hypothesized that the NF-κB, Cytokine regulation, ERK, and TNF-α signaling pathways are the more likely causes of inflammation upon onset of COVID-19. There are several drugs prescribed and used to alleviate the activity of these inflammatory cellular signaling pathways which might be beneficial for developing novel therapeutic modalities against COVID-19. In this review, we briefly summarized the alteration of cellular signaling pathways affected by coronavirus infection, particularly SARS-CoV and MERS-CoV and tabulated the current therapeutic agents approved for previous human diseases.

We provide a summary of various epidemiological parameters related to COVID-19 such as incubation period, serial interval and other parameters. Understanding these parameters is important for developing prevention strategies. SARS-CoV-2 can be transmitted by droplets and close contact, but there is evidence of airborne transmission. Aerosol-generating procedures have been identified as one of the specific risk factors for healthcare workers. Super-spreading events refer to situations where a small number of individuals cause the majority of infections. The basic reproductive number (R0) and the spread parameter (k) are used to characterise the transmissibility of the disease. Estimated values for R0 range from 2 to 3 and the estimated value for k is 0.1.The duration of infectiousness depends on viral load and shedding. Viral load varies according to factors such as clinical spectrum, type of variant and vaccination status. The relationship between viral load and infectivity is not fully understood.With regard to the frequency of symptoms and signs of COVID-19, fever, cough, fatigue and dyspnoea are common. The prevalence of olfactory and gustatory dysfunction (OGD) varies between studies and countries. Age and comorbidities are factors associated with olfactory dysfunction.Estimates of the proportion of asymptomatic patients range from 6% to 96%. Asymptomatic transmission is considered likely and is important for control measures.We reviewed the quantitative semiology of COVID-19 is reported on sensitivity, specificity and likelihood ratios of signs.Finally, we also review risk factors for COVID-19 (including health care workers), co-infections, and epidemiology of variants..

Abstract: The emergence of the COVID-19 pandemic has led to the rapid and worldwide devel-opment and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aims to explore the current knowledge on potential endocrine adverse effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pi-tuitary, adrenal, diabetes, and gonadal events will also be reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. A PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar research were performed. Case reports case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines is accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of endocrine disorders linked to COVID-19 vac-cines.

Number of confirmed cases of COVID-19 caused by SARS-CoV-2 exceeded 5 million as of May 21, 2020. Global average of the case fatality rate of COVID-19 is about 7% so far. There exist variations in case fatality rates among countries. Particularly, Singapore and Qatar have exceptionally low case fatality rates with 0.1% while France’s rate is almost 20%. Since no magic bullet treatment for COVID-19 exists, we investigated SARS-CoV-2 strains specific to Singapore in this study to identify a clade with low pathogenicity. Variant analysis revealed that a clade with variants ORF1ab L3606F, A4489V, S2015R, T2016K, and N P13L is common in Singapore. Based on our analysis of variants and historical case statistics, the clade is dominant in a recent surge. Therefore, we suggest that low case fatality rate of Singapore possibly is attributed to the clade. Although contribution of each variant to the low pathogenicity is not clear, L3606F alone does not accomplish such low pathogenicity from the comparison with case fatality data from Japan, where L3606F is dominant. Further investigation is necessary to conclude to validate this finding.

Phylogenetic trees of coronaviruses are difficult to interpret because they undergo frequent ge-nomic recombination. Here, we propose a new method, named coloured genomic bootstrap (CGB) barcodes, to highlight the polyphyletic origins of human sarbecoviruses and understand their host and geographic ori-gins. The results indicate that SARS-CoV and SARS-CoV-2 contain genomic regions of mixed an-cestry originating from horseshoe bat (Rhinolophus) viruses. First, different regions of SARS-CoV share exclusive ancestry with five Rhinolophus viruses from Southwest China (RfYNLF/31C: 17.9%; RpF46: 3.3%; RspSC2018: 2.0%; Rpe3: 1.3%; RaLYRa11: 1.0%) and 97% of its genome can be related to bat viruses from Yunnan (China), supporting its emergence in Rhinolophus species of this province. Second, different regions of SARS-Cov-2 share exclusive ancestry with eight Rhi-nolophus viruses from Yunnan (RpYN06: 5.8%; RaTG13: 4.8%; RmYN02: 3.8%), Laos (RpBA-NAL103: 3.3%; RmarBANAL236: 1.7%; RmBANAL52: 1.0%; RmBANAL247: 0.7%), and Cam-bodia (RshSTT200: 2.3%), and 98% of its genome can be related to bat viruses from northern Laos and Yunnan, supporting its emergence in Rhinolophus species of this region. Although CGB barcodes are very useful to retrace the origins of human sarbecoviruses, further investigations are needed to better apprehend the diversity of coronaviruses in bats from Cambo-dia, Laos, Myanmar, Thailand and Vietnam.

Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has high infectivity in humans, attributed to the strong affinity of its spike (S) protein to human angiotensin-converting enzyme 2 (ACE2). Here, we analyzed the structural similarity of the S protein between SARS-CoV-2 and other SARS-related coronaviruses (CoVs). Methods We performed multiple alignment analysis of nine amino acid sequences of CoV S proteins from NCBI with MAFFT web-based software, followed by phylogeny analysis. Three-dimensional structure modeling was performed by SWISS-MODEL. We calculated the template modeling score between the S protein of SARS-CoV-2 and that of other SARS-related CoVs. Results The S1 domain of the unclassified CoV RaTG13 (the host of which is the intermediate horseshoe bat) was structurally very similar to that of SARS-CoV-2, implying that RaTG13 could be the origin of SARS-CoV-2. In addition, the folding property of the entire S protein was nearly the same between SARS-CoV-2 and RaTG13 after the PRRA amino acid insertion was removed from SARS-CoV-2. Conclusions RaTG13 could have a high binding affinity to ACE2, similar to SARS-CoV-2, and it is therefore highly likely to infect other animals. Therefore, massive research and monitoring of CoVs in animals is necessary to prevent future COVID-19-like disasters.

The COVID-19 pandemic has posed an unprecedented challenge to healthcare and the available solutions are unsatisfactory. Classical homeopathy may have a role to play in alleviating this burden. Covid cases treated with homeopathy was curated with the intention to provide basic information for further studies. The results are promising although far from being definitive. 367 patients considered were for statistical analysis, the mean age of the participants was 42.75 years, and males and females were 166 and 201 respectively. The mean follow-up period was 6.5 (SD 5.3) days, with a median of 1 homeopathic remedy used per case. 192 patients were diagnosed by RT–PCR, 111 by the WHO clinical criteria and 64 via retrospective antibodies. According to the WHO criteria, 255 were confirmed cases, 61 were probable cases, and 51 were suspected cases. It was seen that 73.8% of covid patients improved under homeopathic treatment, even those among severe disease 78.6%. Correlational analyses showed that presence of fever was associated with more likelihood of improvement and increasing age and a greater number of homeopathic remedies required in a case were associated negatively with improvement. However, it was seen that severe cases were more likely to improve under homeopathic treatment.

Coronavirus Disease-19 (COVID-19) is presently wreaking havoc on public health and socio-economic development. Besides the upper and lower respiratory tract involvement, gastrointestinal symptoms are also reported in COVID-19 patients through gut-lung axis. Finding its way through the feces of infected individuals and other sources, the genetic material of SARS-CoV-2 (ssRNA) is reported widely in wastewater and is being used as a fingerprint for its detection. With millions of cases arriving every day, there is a need to level up the testing speed efficiency. Due to the restricted sampling potential of testing laboratories, clinical testing is unable to track all the symptomatic and asymptomatic cases. Wastewater-based epidemiology (WBE) bestows an auxiliary monitoring tool that will contribute in community level screening. Sample collection, concentration, RNA extraction, quantification and data analysis are the main steps involved in implementation of WBE that can be relied upon as an alarm call for an upcoming wave, emergence of a new variant or any future pandemic. WBE can be a cheaper and more practical alternative to high end and sophisticated clinical testing for community transmission detection. Worldwide, there are more than 300 reports entailing the occurrence of SARS-CoV-2 in wastewater exhibiting unique temporal trends with five of them in India. This review aims to address the present knowledge on surveillance of SARS-CoV-2 in wastewater and its implications.

The novel coronavirus SARS-CoV-2 likely emerged from a wildlife source with transmission to humans followed by rapid geographic spread throughout the globe and severe impacts on both human health and the global economy. Since the onset of the pandemic, there have been many instances of human-to-animal transmission involving companion, farmed and zoo animals, and limited evidence for spread into free-living wildlife. The establishment of reservoirs of infection in wild animals would create significant challenges to infection control in humans and could pose a threat to the welfare and conservation status of wildlife. We discuss the potential for exposure, onward transmission and persistence of SARS-CoV-2 in an initial selection of wild mammals (bats, canids, felids, mustelids, great apes, rodents and cervids). Dynamic risk assessment and targeted surveillance are important tools for the early detection of infection in wildlife, and here we describe a framework for collating and synthesising emerging information to inform targeted surveillance for SARS-CoV-2 in wildlife. Surveillance efforts should be integrated with information from public and veterinary health initiatives to provide insights into the potential role of wild mammals in the epidemiology of SARS-CoV-2.

Today, we are all threatened by an unprecedented pandemic: COVID-19. How different is it from other coronaviruses? Will it be attenuated or become more virulent? Which animals may be its original host? In this study, we analyzed 377 publicly available complete genome sequences for the COVID-19 virus, the previously known flu-causing coronaviruses (HCov-229E, HCov-OC43, HCov-NL63 and HCov-HKU1) and the lethal, pathogenic P3/P4 viruses, SARS, MERS, Victoria, Lassa, Yamagata, Ebola, and Dengue. We found strong similarities between the current circulating COVID-19 and SARS and MERS, as well as COVID-19 in rhinolophines and pangolins. On the contrary, COVID-19 shares little similarity with the flu-causing coronaviruses and the other P3/P4 viruses. Strikingly, we observed divergence of COVID-19 strains isolated from human hosts has steadily increased from December 2019 to March 2020, suggesting COVID-19 is actively evolving in human hosts. From all existing human COVID-19 genome sequences, we calculated the first common model that represents the shared sequences of the human COVID-19 strains, which provides important information for vaccine and antibody development. Geographic and time-course analysis of the evolutionary trees of the human COVID-19 reveals possibly heterogeneous evolutional paths among strains from 21 countries. This finding has important implications to the management of COVID-19 and the development of vaccines.

In December 2019, pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China. Early in 2020, the World Health Organization (WHO) announced a new name for the 2019-nCoV-caused epidemic disease: coronavirus disease 2019 (COVID-19) and declared COVID-19 to be the sixth international public health emergency. Cellular co-infection is a critical determinant of both viral fitness and infection outcome and plays a crucial role in shaping the host immune response to infections. In this study, sixty-eight public next-generation sequencing libraries from SARS-CoV-2 infected patients were retrieved from the NCBI Sequence Read Archive database using SRA-Toolkit. Using an alignment-free method based on K-mer mapping and extension, SARS-CoV-2 was identified in all except three patients. Influenza A H7N9 (3/68), Human immunodeficiency virus 1 (1/68), rhabdovirus isolate (3/68), Human metapneumovirus (1/68), coronaviruses NL63 (1/68), Parvovirus (1/68), Simian virus 40 (1/68), and hepatitis virus (1/68) genome sequences were detected in SARS-CoV-2 infected patients.

Cross-sectional survey was conducted to capture the true extent of COVID-19 exposure among students and staff of Polytechnic High School (PHS). Random cluster sampling was carried out between May 19 and August 18, 2022, after the fourth wave of COVID-19 transmission. IgM and IgG SARS-CoV-2 antibodies were screened using WANTAI SARS-CoV-2 ELISA assays. Seroprevalence and descriptive statistics were calculated. Moreo-ver, the association between seropositivity and different factors (age, gender, preventive measures comorbidity, and symptoms, etc.) was determined using Logistic Regression. The overall IgG and IgM seroprevalence were 92% and 6.91% respectively. We found a higher IgM seroprevalence in men than women (9.4% vs. 5.6%) and a lower IgM seroprevalence in (18-25) age group compared to (55-65) years. Low compliance with preventive measures was found with a significant IgM seroprevalence depending on non-respect of social distancing (p = 0.008). A total of 70% of participants presented symptoms linked to COVID-19 at the moment of the survey. Results revealed a significant difference according to IgG seroprevalence among participants who declared fa-tigue symptoms 92.06% compared to those who did not 80.39% (p = 0.0027). IgM seropositivity was associated with Body Mass Indice (BMI) categorized (O.R. 0.238, p = 0.043), ethnic group (O.R. 0.723, p = 0.046) and marital status (O.R. 2.399, p = 0.021). Moreover, IgG seropositivity was associated with Chronic sinusitis comorbidity (O.R. 0.238, p = 0.043) and vaccination status (O.R. 4.741, p < 0.001). The majority of students and staff have al-ready been exposed to SARS-CoV-2 and confirm the circulation of SARS-CoV-2 in PHS at the time of the survey. Our results underline the importance of sero-epidemiological surveys to estimate the real impact of the COVID-19 pandemic in a community and to monitor disparities in antibody response in the population.

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.

The reverse transcription quantitative polymerase chain reaction (RT-qPCR) is an established tool for the diagnosis of RNA pathogens. Its potential for automation has caused it to be used as a presence/absence diagnostic tool even when RNA quantification is not required. This technology has been pushed to the forefront of public awareness by the COVID-19 pandemic, as its global application has enabled rapid and analytically sensitive mass testing, with the first test targeting three viral genes published within days of the publication of the SARS-CoV-2 genomic sequence. One of those, targeting the RNA-dependent RNA polymerase gene, has been heavily criticised for supposed scientific flaws at the molecular and methodological level and this criticism has been extrapolated to doubts about the validity of RT-qPCR for COVID-19 testing in general. We have analysed this assay in detail and our findings reveal some limitations, but also highlight the robustness of the RT-qPCR methodology for SARS-CoV-2 detection. Whilst our data show that some errors can be tolerated, it is always prudent to confirm that primer and probe sequences complement their intended target, since when errors do occur, they may result in a reduction in the analytical sensitivity. However, in this case it is unlikely that a mismatch will result in poor specificity or significant number of false positive SARS-CoV-2 diagnoses, especially as this is routinely checked by diagnostic laboratories as part of their quality assurance.

The detection of SARS-Cov-2 in the sewage and water resources has increased the awareness among the people about the possibility survival of SARS-Cov-2 in the environment and the potential to transmit into the human through food chain or water resources. Moreover, the surface contaminated by the virus need to be disinfected frequently by using an effective disinfectant, the current chapter discussed the efficiency of the most traditional treatment process of the sewage and wastewater, and their role in the elimination of the virus as well as the sterility assurance level concept. Moreover, the chemical disinfectant used currently and their temporary efficiency has been reviewed.

Covid-19 has now become a public health concern worldwide. The infection primarily involves the respiratory tract. Hitherto, some Covid-19 pneumonia patients carry the viral nucleic acids, and the active virus was detected in stool specimens. The virus discharged with feces is a potential contagious source. In the present study, three Covid-19 respiratory tract infection patients showed no gastrointestinal symptoms, and two were positive for viral nucleic acids in anal swab specimens remained positive 6 and at least 14 days after virus turned negative in the respiratory tract, respectively (details of the patients were listed in Fig 1). Thus, for Covid-19-infected patients with or without gastrointestinal symptoms, viral nucleic acids in stool specimens or anal swab specimens should be focused on for testing in order to decide the isolation duration of the patient.

Understanding the dynamics of humoral immune responses throughout the COVID-19 pandemic is crucial for optimizing vaccine strategies. This study aimed to investigate the impact of infection and vaccine-induced immunity on the Albanian population from August 2021 to August 2022. Two independent samples from the Albanian general population were analyzed using an ELISA method to assess IgG class anti-Spike (S1) and anti-Nucleocapsid (N) SARS-CoV-2 antibodies. The results revealed a robust immune response among vaccinated individuals with prior COVID-19 infection who received only one vaccine dose. In the 2022 cohort, most individuals who received one vaccine dose achieved comparable seropositivity and antibody levels to those who received two doses. However, individuals aged 61 and over required two or three vaccine doses to reach the same level of immune response as the younger population. Notably, the time elapsed since infection or vaccination did not significantly impact the immune response. These findings highlight the importance of hybrid immunity and suggest that one vaccine dose may be sufficient for most individuals with prior COVID-19 infection. However, additional doses are necessary for optimal protection in older individuals. This study provides unique insights into humoral immune response dynamics that can be used to refine ongoing COVID-19 population vaccination strategies for middle-income countries with low vaccination coverage.

Severe Covid-19 disease is associated with endothelial infection, viraemia, and multi-organ dysfunction. The process through which SARS-CoV2 causes severe disease is yet to be determined. Here, we propose that in severe Covid-19 infection, SARS-CoV2 reaches the host bloodstream by infecting endothelial cells through their basal surface. This occurs, independently of ACE2, through CD147, a putative SARS-CoV2 receptor. The pathway proposed here encourages research on the mechanisms mediating endothelial cell infection in Covid-19.

SARS-CoV 2 also known as COVID-19 is a fast spreading coronavirus related disease that emerged from China in December 2019 and is currently attained the status of a pandemic. There are currently no drugs/ vaccines against the same and moreover limited diagnostic tests to identify the infection. Additionally, these tests are expensive and hence are exclusive for very highly suspected cases of the disease especially in developing countries. This is causing an under-diagnosis which is an alarming state of affairs, as even a single missed SARS-CoV 2 case would spread the disease exponentially and keep it in the community. Through this entirely in silico study, we have developed a cheaper and faster diagnostic method based on simple PCR and restriction enzyme digestion, commonly used in restriction fragment length polymorphism (RFLP) tests. Through comparative genomics, we found the closest neighbours of SARS-CoV 2 then found the highly conserved regions of the genome which were absent in SARS-CoV 1, its closest neighbour. Then we found restriction sites for various enzymes followed by designing of PCR primers flanking those sites. We have found the primer pair to produce a 401 bp amplicon and when digested by SwaI enzyme, it produces two fragments of lengths 216 bp and 185 bp. As an internal control, GAPDH primers are pooled with the SARS-CoV 2 primers as the patient sample will also include human RNA mixed with the viral RNA. This primer pair gives an amplicon of 131 bp and hence a negative sample should show a single band of 131 bp while a positive digested sample will give three bands of 401 bp, 216 bp and 131 bp. The primers are specific to SARS-CoV 2 only and can additionally be used for SYBR green based real time quantification of viral load. The developed tests have not yet been tested in vitro due to stressed out working hours in the only pathogenic virus handling laboratory in our institute. Nonetheless, this study works as a head start for other laboratories to rapidly test the suggested protocols in vitro and make available a cheaper alternative test for SARS-CoV 2 which would especially be beneficial for the lower to middle income countries.

Evidence for the potential for airborne transmission of SARS-CoV-19 continues to accumulate, with important implications for healthcare workers, as well as the general public. Three lines of evidence support this conclusion.

Since the first description of SARS-CoV-2 in China in 2019, thousands of variants have emerged worldwide. For some of them, the constellation of mutations caused changes in virus biology, pathogenicity, infectivityity and transmissibility resulting in dissemination throughout the world. Gamma variant (P.1) differs from SARS-CoV-2 Wuhan strain (B.1) by 12 amino acids in the Spike (S) protein, and presented mutations related to greater affinity for the receptor angioten-sin-converting enzyme 2 (ACE-2) and/or immune escape. The Gamma variant and subvariants were responsible for the second wave of COVID-19 in the Brazilian city of Manaus, characterized by high mortality and rapid transmission. The ability of variants to induce cytokine production may be closely related to their pathogenicity. Herein we observed that there was no significant difference in the quantity of cytokines among macrophages or neutrophils infected with P.1 and B.1 strains. Also, no significant difference was observed in the absolute number of macrophages and neutrophils infected with these variants. Furthermore, no evidence of SARS-CoV-2 replication was observed in macrophages when infected by the two analyzed variants. Our findings suggest that the difference in the epidemiological outcome observed during the P.1 variant spread when compared to B.1, it is not explained by differences in the quantity of cytokines and absolute number of macrophages or neutrophils. Through bioinformatics analysis of the S protein, we observed that the physicochemical differences between the variants and subvariants of P.1, probably refer to the degree of infectivity, due to the impact caused in the recognition of antibodies and receptor af-finity

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly to most parts of the world, causing high numbers of deaths and significant social and economic impacts. SARS-CoV-2 is a novel coronavirus with a suggested zoonotic origin and with the potential for cross-species transmission among animals. Antarctica can be considered the only continent free of SARS-CoV-2 although at the end of the 2019-2020 tourist season, at least one SARS-CoV-2 positive tourist visited the Antarctic Peninsula. Therefore, concerns have been expressed regarding the potential human introduction of this virus to the continent through the activities of research or tourism with potential effects including those related to human health, but also the potential for virus transmission to Antarctic wildlife. This reverse-zoonotic transmission risk to Antarctic wildlife is assessed considering the available information on host susceptibility, dynamics of the infection in humans, and contact interactions between humans and Antarctic wildlife. Measures to reduce the risk are proposed as well as the identification of knowledge gaps related to this issue.

Background: the devastating outbreak of COVID-19 poses serious challenges for the diagnostics laboratories, which are often facing global shortage of reagents and equipment. With the aim of increasing the diagnostic throughput for SARS-CoV-2 molecular test, the purpose of this study was to validate an additional RNA extraction method respect to those already recommended by WHO and the US Centers for Disease Control and Prevention (CDC). Methods: a new protocol for RNA extraction from nasopharyngeal swab was set up, adapting the Qiagen RNeasy 96 plate and validated on a set of 100 clinical samples analyzed in parallel by Roche-Magnapure method (already recommended by CDC guidelines). Results: the internal control and target genes analysis showed a good agreement between the two extraction methods indicating that the two methods can be considered equivalent and that the RNeasy-adapted method can be applied for the SARS-CoV-2 diagnostics. The addition of this new extraction method resulted in a throughput increase for SARS-CoV-2 molecular test of about 2000 samples/month during the initial months of the pandemic emergency in which the lack of reagents for the extraction led to an insufficient sample processing throughput of the analysis of the swabs.

It has been a long time since the world has experienced a pandemic with such a rapid devastating impact as the current COVID-19 pandemic. The causative agent, the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is further unusual in that it appears capable of infecting many different mammal species. As a significant proportion of people worldwide are infected with SARS-CoV-2 and may spread the infection unknowingly before symptoms occur or without any symptoms ever occurring, there is a non-negligible risk of humans spreading SARS-CoV-2 to wildlife, in particular mammals. Because of SARS-CoV-2’s evolutionary origins in bats and reports of humans transmitting the virus to pets and zoo animals, regulations for prevention of human-to-animal transmission have so far focused mostly on these animal groups. Here, we summarize recent studies and reports that show that a wide range of distantly related mammals are likely susceptible to SARS-CoV-2 and that susceptibility or resistance to the virus is in general not predictable, or only to some extent, by phylogenetic proximity to known susceptible or resistant hosts. In the absence of solid evidence on the SARS-CoV-2 susceptibility/resistance for each of the >5,500 mammal species, we argue that sanitary precautions should be taken when interacting with any mammal species in the wild. Preventing human-to-wildlife SARS-CoV-2 transmission is important for protecting these (sometimes endangered) animals from disease, but also to avoid establishment of novel SARS-CoV-2 reservoirs in wild animals. The risk of repeated re-infection of humans from such a wildlife reservoir could severely hamper SARS-CoV-2 control efforts. For wildlife fieldworkers interacting directly or indirectly with mammals, we recommend sanitary precautions such as physical distancing, wearing face masks and gloves, and frequent decontamination, which are very similar to regulations currently imposed to prevent transmission among humans.

The disease COVID-19 is highly infectious, and infectious in asymptomatic incubation period. The national epidemic development has been effectively controlled and continues improving, especially in areas outside Hubei province. Such periodical results were achieved by the joint efforts of the whole society, including not only the hard work and dedication of the front-line medical workers but also the active cooperation of the general public. The strict epidemic prevention and control measurements have brought remarkable control results. In the present study, the basic infection number of the coronavirus R0 (basic replication number of the infection) before and after prevention and control measurements was simulated to elaborate the measurements of the Chinese government on epidemic prevention and control, providing reference for the people around the world.

Background: Early-stage interventions in a potential pandemic are important tounderstand as they can make the difference between runaway exponential growththat is hard to turn back and stopping the spread before it gets that far. COVID-19 is an interesting case study because there have been very different outcomesin different localities. These variations are best studied after the fact if precisionis the goal; while a pandemic is still unfolding less precise analysis is of value inattempting to guide localities in the early stages to learn lessons of those that pre-ceded them. Methods: I examine three factors that could differentiate strategy: asymptomaticspread, differences in use of the Bacillus Calmette-Guerin (BCG) tuberculosis vac-cine and cloth face masks.Results:Differences in disease progression as well as the possibility of alternativestrategies to prevent COVID-19 from entering the runaway phase or damping itdown later can be elucidated by a study of asymptomatic infection. A study todemonstrate not only what fraction are asymptomatic but how contagious they arewill also inform policy on universal mask wearing. Conclusions: While a COVID-19 outbreak is at a level that makes accurate trace-and test possible, investigation of asymptomatic transmission is viable and shouldbe attempted to enhance understanding of spread and variability in the disease aswell as policy options for slowing the spread.

The most severe threat that the Covid-19 pandemic poses to the global economy is the need to choose between human lives and livelihoods. Bangladesh must assess the implications of such impacts on Bangladesh's macro-financial scenario to maintain the economy's current high growth trajectory. The paper outlines the major Covid-19 shock wave transmission channels to the four major sectors of the Bangladesh economy. Authorities around the world have taken every precaution possible to halt the spread of the pandemic. An aggregate transmission framework that includes these four sectors is required to contain the impact of Covid-19 can propagate through these sectors and eventually impact macro-financial stability.

The outbreak of recently identified 2019 novel coronavirus (2019-nCOV) infection has become a world-wide health threat. Currently, more information is needed for further understanding the transmission, clinical characteristics, and infection control procedures of 2019-nCOV. Recently, the role of the eye in transmitting 2019-nCOV has been intensively discussed. Previous investigations about other high infectious human COVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide helpful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, mechanisms of human CoVs infection, and infection control procedures. The role of the eye in the transmission of SARS-CoV and 2019-nCOV is discussed. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of ocular surface and upper respiratory tract is connected by nasolacrimal duct and share same entry receptors for some respiratory viruses. The eye is rarely involved in human CoVs infection, conjunctivitis is quite rare in patients with SARS-CoV and 2019-nCoV infection, and COV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with SARS-CoV and 2019-nCoV infection is also very low, which imply that the eye is neither a preferred organ of human COVs infection, nor is a preferred gateway of entry for human COVs to infect respiratory tract. However, pathogens exposed to the ocular surface might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through lacrimal duct, and then cause respiratory tract infection. Considering close doctor-patient contact is quite common in ophthalmic practice which are apt to transmit human COVs by droplets and fomites, hand hygiene and personal protection are still highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide since its emergence and is causing the disease COVID-19. According to WHO, this is a zoonotic disease. Several cases have already been discovered where companion animals were affected due to virus spillover from humans, however, the symptoms are mild in most cases. We report the first documented case of SARS-CoV-2 infection and death of a domestic cat (Felis silvestris catus) in Hungary, where no other disease could be detected.

(1) Background: It is unclear whether the reported presenting clinical features of coronavirus disease 2019 (COVID-19) are useful in identifying high-risk patients for early testing and isolation in the emergency department (ED). We aimed to compare the exposure history, clinical, laboratory, and radiographic features of ED patients who tested positive and negative for COVID-19; (2) Methods: We conducted a case-control study in seven EDs during the first five weeks of the COVID-19 outbreak in Hong Kong. Thirty-seven laboratory-confirmed COVID-19 patients were compared with 111 age- and gender-matched controls; (3) Results: There were no significant differences in patient characteristics and reported symptoms between the groups, except patient-reported fever. A positive travel history or contact history was the most significant predictor for COVID-19 infection. After adjustment for age and presumed location of acquiring the infection in Wuhan/Hubei, patient-reported fever (OR 2.6, 95% CI 1.1 to 6.3), delayed presentation (OR 5.0, 95% CI 2.0 to 12.5), having medical consultation before ED presentation (OR 7.4, 95% 2.9 to19.1), thrombocytopenia (OR 4.0, 95% CI 1.6 to 9.7), raised lactate dehydrogenase (OR 5.9, 95% CI 1.9 to 18.5), haziness, consolidation or ground-glass opacity on chest radiography (OR 5.6, 95% CI 2.0 to 16.0), and bilateral changes on chest radiography (OR 13.2, 95% CI 4.7 to 37.4) were associated with a higher odds of COVID-19 separately while neutrophilia was associated with a lower odds (OR 0.3, 95% CI 0.1-0.8); and (4) Conclusions: This study highlights several features that may be useful in identifying high-risk patients for early testing and isolation while waiting for test result. Further studies are warranted to verify the findings.

The novel coronavirus SARS-CoV2 (CoV2) emerged in December 2019. This virus has 88% genomic similarity with SARS-CoV (CoV), and both viruses largely depend on their main protease (M^pro) to regulate infection. M^pro thus represents an attractive target for anti-SARS drug design. The CoV and CoV2 M^pro are 97% identical at the sequence level, with 12 variable residues, and their X-ray structures appear similar. We thus structurally analysed how these variable residues affect the intra-molecular interactions between key residues in the CoV2 M^pro active-site. Compared to CoV M^pro, the 12 divergent residues in CoV2 M^pro exhibit modified intra-molecular interaction networks that ultimately restructure the molecular micro-environment. These altered networks also indirectly affect the networks of other active-site residues at the entrance (T26, M49 and Q192) and near the catalytic region (F140, H163, H164, M165 and H172) of the M^pro. This suggest CoV2 indirectly (via neighbours) reshape key molecular networks around the M^pro active-site. It seems that the CoV2 M^pro deceives us with its apparent structurally identical to the CoV M^pro while this viral system accumulates mass mutations (12 variable residues) at key positions. Some of these identified CoV2 M^pro networks at the active-site might guide design of efficient CoV2 M^pro inhibitors.

Background: The rise of new SARS-CoV-2 mutations brought challenges and progress in the global fight against COVID-19. Mutations in spike and accessory genes affect transmission, vaccine efficacy, treatments, testing, and public health strategies. Monitoring emerging variants is crucial to halt virus spread. Methods: 44 nasopharyngeal/oropharyngeal swabs from Kenyan patients were sequenced with the Illumina platform. Galaxy's bioinformatic tools were used for genomic analysis. SARS-CoV-2 genome classification was done using PANGOLIN and mutation annotation with the COVID-19 Annotator tool. Results: The study showed 5 clades to be circulating in the region. 38(86%) were BA.1.1; 2(5%) were BA.1.1.1; 1(2%) was BA.1; 1(2%) was BA.1.14 and 2(5%) were AY.46. These clades had a cumulative of 173 mutations among them with 50 novel mutations. Forty-eight of these novel mutations occurred in a low frequency of 2.3% of the sequences tested while the other two, S:R214R, and NSP2:A555A, were for 43.2% and 18.2% of the cases respectively. Conclusions: The high-frequency novel mutations were synonymous mutations, a phenomenon that was previously viewed as phenotypically silent but recent studies indicate they can affect viral fitness with potential functional associations. These findings add to the understanding of the SARS-CoV-2 virus future evolutionary and immunological dynamics in the region

The possible future emergence of new SARS-CoV-2 virus variants pushes the development of new chemoprophylaxis protocols complementary to the unspecific and specific immune-prophylaxis measures currently used. The SARS-CoV-2 virus is particularly sensitive to oxidation due to the relevant positive electrical charge of its spike protein used as a ligand for target cells. The present study evaluated the safety and efficacy of a new oxidant preparation, liquid hyperoxygen (IOL), to neutralize the SARS-CoV-2 virus. IOL was incubated with throat swabs containing a human wild-type virus. The samples were then incubated with cells expressing the ACE2 receptor and therefore very sensitive to SARS-CoV-2 infection. The ability to neutralize SARS-CoV-2 was determined by assessing the amount of viral nucleic acid inside cells by PCR. The results obtained indicate that IOL, even at considerable dilutions, is capable, after incubation times of less than 30 min and even equal to 5 min, to completely inhibit SARS-CoV-2 infection. This inhibitory effect has been shown to be due to the oxidizing capacity of the IOL. This oxidizing capacity is exerted towards the virus but does not damage eukaryotic cells either in the in vitro or in the in vivo skin model. Obtained results indicate that the use of IOL, a hydrophilic liquid mixture saturated with highly reactive oxygen and nitrogen species, is a new powerful, safe, and effective tool for preventing possible future outbreaks of COVID-19 disease.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral genome is an RNA virus consisting of approximately 30,000 bases. As part of testing efforts, whole genome sequencing of human isolates has resulted in over 1,600 complete genomes publicly available from GenBank. We have performed a comparative phylogenetic analysis of the sequences, in order to detect common mutations within the population. Analysis of variants occurring within the assembled genomes yields 417 variants occurring in at least 1% of the completed genomes, including 229 within the 5’ untranslated region (UTR), 152 within the 3’UTR, 2 within intergenic regions and 34 within coding sequences.

We applied a generalized SEIR epidemiological model to the recent SARS-CoV-2 outbreak in the world, with a focus on Italy and its Lombardia, Piemonte, and Veneto regions. We focus on the application of a stochastic approach in fitting the model numerous parameters using a Particle Swarm Optimization (PSO) solver, to improve the reliability of predictions in the medium term (30 days). We analyze the official data and the predicted evolution of the epidemic in the Italian regions, and we compare the results with data and predictions of Spain and South Korea. We link the model equations to the changes in people’s mobility, with reference to Google’s COVID-19 Community Mobility Reports. We discuss the effectiveness of policies taken by different regions and countries and how they have an impact on past and future infection scenarios.

The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. Previous studies have demonstrated the efficacy of functional inhibitors of acid sphingomyelinase (FIASMA) against infections with various viruses, including early variants of SARS-CoV-2. This work investigated whether the acid sphingomyelinase inhibitors fluoxetine and sertraline, usually used as antidepressant molecules in clinical practice, can inhibit the replication of the former and recently emerged SARS-CoV-2 variants in vitro. Fluoxetine and sertraline potently inhibited the infection with pseudotyped virus like particles and SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1 and omicron BA.5. These results highlight fluoxetine and sertraline as priority candidates for large-scale phase 3 clinical trials at different stages of SARS-CoV-2 infections, either alone or in combination with other medications.

Background: The use of animal models for biomedical research provides us with a convenient and feasible route to establish causal relationships by recapitulating the temporal sequence of events in a controlled environment with a potential to manipulate the variables at multiple levels including genetic, protein, physiological or environmental. Objectives: The current review was conducted to gain insights into various animal models for the SARS-CoV-2 virus. Material and Methods: A literature review (PUBMED, PUBMED Central, PMC, Google Scholar, Google search engine) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines performed in early April 2020 revealed 9 articles of interest. Search terms included covid 19, covid-19, novel corona virus, SARS-CoV-2, animal models, experimental models, laboratory models & covid 19 animal models. Two independent reviewers extracted the data; the third reviewer was involved in case of discrepancy. Results: SARS-CoV-2 shares an identical receptor binding domain with the SARS-CoV virus and has a superior binding affinity to the host ACE2. Based on this, the role of rhesus macaques, golden Syrian hamsters, transgenic hACE2 mice and ferrets as animal models have been studied. All four animals are susceptible to infection with SARS-CoV-2 with variable clinical presentation but universal recovery. The respiratory tract is primarily involved in all four models. Involvement of intestines was also seen in at least one study in each animal. Transfer to naïve animals in close contact has been documented in case of hamsters and ferrets. Seroconversion was documented in all although the role of convalescent sera was tested in hamsters only, with positive results though. Air-borne transmission was documented in ferrets and the possibility of feco-oral transmission was suggested for hamsters. The possibilities of recurrence and re-infection were ruled out by experiments upon the rhesus macaques. The fulfilment of Koch’s postulates has been highlighted. Discussion: The various studies available on animal models have been able to establish models of infection and transmission that recapitulate different aspects of disease in humans. However, the response between different animals and the same animal in different experiments is not completely coherent. Some of them do not manifest the disease clinically while others behave differently at molecular and immunological levels. Moreover, the physiology of these animals is not identical to human beings and the findings may not be extrapolated to human beings in an ‘as-is’ manner. Conclusions: The review acknowledges the achievements made by these experiments in a short span of time and highlighted the urgent need for a deeper dive in search of a quintessential animal model which can be studied for efficacy and safety of newer drugs and vaccines before a make-shift from the petri-dish to the human body can be contemplated.

Acute respiratory viruses (ARVs) are leading cause of diseases in human worldwide. High risk individuals including children and elderly could potentially develop severe illness that could result in hospitalization or death in the worst case. Most common ARVs are Human respiratory syncytial virus, Human Metapneumovirus, Human Parainfluenza Virus, rhinovirus, coronaviruses (including SARS and MERS CoV), adenoviruses, Human Bocavirus, enterovirus (-D68 and 71), and influenza viruses. The olfactory deficits due to ARVs infection is a common symptom among patients. This mini review provides an overview of the role of SARS-CoV-2 and other common ARVs in the development of human olfactory pathophysiology. We highlight the critical need for understanding the signaling underlying the olfactory dysfunction and the development of therapeutics for this wide-ranging category of AVRs to restore the altered or loss of smell in affected patients.

With the arrival of SARS-CoV-2 vaccines, a new stage of the pandemic commenced, with new challenges ahead. During the coming months, countries will be implementing their COVID-19 vaccination programs depending on their implementation of vaccine availability and its prescription on risk stratification. Although children will not benefit from active immunization programs, now, with the beginning of the era of the anti-COVID19 vaccines, the suffering of children can no longer be ethically tolerated or neglected. The time has come to provide specific lasting strategies for children living in the COVID-19 era. Here we propose a child-focused indirect COVID-19 vaccination strategy.For better or worse, children depend on their natural caregivers (adults) and the rest of society for their well-being and achieving their full potential. We believe that including in the priority categories also those adults in close contact with children could ensure a safety net of child protection.A child-focused vaccination strategy would allow the faster return to "normality" for children and their families. Such an approach would not only enable the reopening and continuity of essential services for children but also would allow adults to return to their routine economic/productive activities.

Spike (S) protein of Coronaviruses help in receptor attachment and virus entry into the host cells. While S protein is required for virus entry, it is also important as an immunogen as it is the most accessible part of the virus architecture. S protein form knob like structures (viral spikes) protruding outwards in the form of homotrimers containing an S1 and S2 as monomers. Mutations in structural proteins of virus play crucial role in determining virulence and also in many instances influencing emergence of antibody escape variants and cellular tropism. In this paper we have performed in depth analyses of spike protein sequences from various parts of the world and tried to correlate the data with possible functional relevance of such mutations.

The effect of the COVID-19 pandemic in a developing country like Bangladesh is enormous. A research conducted by South Asian network of Economic Modelling predicted that the pandemic could double the poverty. But it is not that only the socioeconomic condition is dropping in Bangladesh, the impact of COVID-19 pandemic is manifold. The poor condition of Bangladesh's health sector has also been exposed due to the pandemic. People are not getting proper treatment due to lack of isolation beds, oxygen, ICU etc. The health sector of Bangladesh is not much developed and now with this pandemic it has become impossible to provide treatment facility for all the patients. Education sector, which is the backbone of a country,has also been greatly affected by the pandemic. We know that different types of cultural occasions are an inherited tradition of Bangladesh, COVID-19 have not even spared these traditions, all the cultural programes and festivals have been cancelled due to this pandemic.In this paper, our aim is to present the present status of all these sectors.

An outbreak caused by coronavirus disease 2019 (COVID-19) occurred in Wuhan City, Hubei Province, China, in December 2019. Up to March 2, 2020, at least 80180 cases have been reported. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province, or exposed to symptoms. Some patients got infected only from asymptomatic contacts. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection only from asymptomatic contact.

Covid-19 is often related to hyperinflammation that drives lung or multi-organ injury. The immunopathological mechanisms that cause excessive inflammation following SARS-Cov-2 infection are under investigation while different approaches to limit hyperinflammation in affected patients are being proposed. Here, a computational protein-protein interaction network approach was used on recently available data to identify possible Covid-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-Cov-2 cellular receptors and their directly associated proteins, led to the mining of a robust neutrophil response signature and multiple relevant inflammatory genes. Second, analysis of RNA-seq datasets of lung epithelial cells infected with SARS-Cov-2 revealed that infected cells specifically expressed neutrophil-attracting chemokines, further supporting the likely role of neutrophils in Covid-19 inflammation. Third, analysis of RNA-seq datasets of bronchoalveolar lavage fluid from Covid-19 patients, identified neutrophil-specific genes and chemokines. Different immunoregulatory and neutrophil-relevant molecules mined here such as, TNFR, IL8, CXCR1, CXCR2, ADAM10, GPR84, MME-neprilysin, ANPEP and LAP3 are druggable and might be therapeutic targets in efforts to limit SARS-Cov-2 inflammation in severe clinical cases. The role of neutrophils in Covid-19 needs to be studied further.

Although the anti-COVID-19 vaccination has proved to be an effective preventive tool, "break-through infections" have been documented in patients with complete primary vaccination course. Most of the SARS-CoV-2 neutralizing antibodies pro-duced after SARS-CoV-2 infection target the spike protein receptor-binding domain which has an important role in facilitating viral entry and infection of the host cells. SARS-CoV-2 has demonstrated the ability to evolve by accumulating mutations in the spike protein to escape the humoral response of the host. The aim of this study is to compare the titers of neutralizing an-tibodies against the variants of SARS-CoV-2 by analyzing the sera of recovered and vaccinated healthcare workers (HCWs). 293 HCWs were enrolled and divided into three cohorts as follows: 91 recovered from SARS-CoV-2 infection (nVP); 102 vac-cinated who became positive after the primary cycle (VP); 100 vaccinated with complete primary cycle who concluded the follow-up pe-riod without becoming positive (VN). Higher neutraliza-tion titers were observed in the vaccinated subjects’ arms com-pared to the nVP arm. Differences in neutralization titers between arms for single variant were statistically significant (p<0.001) except for titers against the Alpha variant (p<0.05) between nVP and VP. Within the nVP group, the number of subjects with the absence of neutralizing antibodies was high. The presence of high-er titers in patients with a complete primary cycle compared to patients recovered from the infec-tion suggests a better efficacy of artificial immunization compared to natural im-munization, further encouraging the promotion of vaccination even in subjects with previous infection.

The pandemic associated with SARS-CoV-2 is a worldwide public health challenge. The WHO has proposed to achieve 70% COVID-19 vaccination coverage in all countries by mid-2022. Nevertheless, the prevention strategy based on COVID-19 vaccination and other applied prevention measures have not been sufficient to prevent SARS-CoV-2 epidemic waves. The study assessed the vaccination coverage that would be required to establish herd immunity against SARS-CoV-2 by taking into account virus transmissibility (Ro values from 1.1 to 10) and Covid-19 vaccination effectiveness. The study found that Covid-19 vaccination programs could establish herd immunity against SARS-CoV-2 with Ro &lt; 3 with levels of Covid-19 vaccination effectiveness of 10−100% and against viruses with Ro values ranging from 3 to 10 with levels of Covid-19 vaccination effectiveness of 70−100%. Factors reducing Covid-19 vaccination effectiveness (emergent variants, reinfections, high risk individuals) and factors increasing SARS-CoV-2 transmissibility (close settings) increased percentages of vaccination coverage that would be required to establish herd immunity. The vaccination coverage objective of 70% could be adequate against SARS-CoV-2 with Ro values of 1.1−2.5, while percentages of vaccination coverage of 80% and 90% could be more adequate against viruses with Ro values of 2.5−3.5 and &gt;3.5, respectively. On February 2022, the vaccination coverage for complete vaccination was lower than 70% in 73.2% of the countries of the world. Percentages of Covid-19 vaccination coverage must be increased in most countries of the world to increase individual and herd immunity levels in the population.

The COVID-19 pandemic has posed a significant threat to society in recent times, endangering human health, life, and economic well-being. The disease spreads quickly due to the highly infectious SARS-CoV-2 virus, which has undergone numerous mutations. Despite intense research efforts by the scientific community since its emergence in 2019, no effective therapeutics have been discovered yet. While some repurposed drugs have been used to control the global outbreak and save lives, none have proven universally effective, particularly for severely infected patients. Although the spread of the disease is generally under control, anti-SARS-CoV-2 agents are still needed to combat current and future infections. This study reviews some of the most promising repurposed drugs containing indolyl heterocycle, which is an essential scaffold of many alkaloids with diverse bio-properties in various biological fields. The study also discusses natural and synthetic indole-containing compounds with anti-SARS-CoV-2 properties, as well as computer-aided drug design (in-silico studies) for optimizing anti-SARS-CoV-2 hits/leads.

The Saudi government has undertaken rapid and swift actions, such as suspending Omrah and holding international flights. Such affirmative actions enhanced citizens and residents’ confidence in the government officials’ ability to fight the pandemic. However, there are more than 361,178 reported cases of Covid-19 with 6131 deaths as of December 22, 202. As nurses are the largest component of the health care workforce in Saudi Arabia, it is important that they are trained and have the skills and resources to adapt, whether on the frontline of a crisis or in a clinical environment. Nurses play a key function in fulfilling the needs of medical treatment by being the most important part of the health care delivery system.

Culture, gender and religion are closely linked each other’s, profoundly affect the role of each person within the Society, and also affect the ability to access to the health resources. We are now living a worldwide crisis due to the SARS-CoV-2 pandemic. In order to appropriately tackle it, an alliance between science, politics and citizens is needed. In this article, we summarize current evidences of how religions can represent, on one hand, a risk moment for spreading the virus (in relation with overcrowded events), on the other, a precious opportunity to engage people, and in particular minorities, in fighting the pandemic. To win this fight, we need a multicultural approach that takes into account every aspect of human life, and among these religion, which influences so much culture, everyday life and well-being.

A change in biological properties of the SARS-CoV-2 virus can enhance its transmissibility and virulence, complicate the disease course, and reduce the effectiveness of anti-viral therapy and vaccination. We have studied 16 genetic lineages of the Omicron variant. The viral reproduction course was analyzed based on plaque morphology in the agar layer and the maximum titer in Vero E6 cells. BALB/c mice and Syrian hamsters were used as animal models. Viral load and infectious SARS-CoV-2 titer were determined in the nasal tissue and lungs. The severity of infectious process was assessed using histological methods. An increased plug size was observed in CH.1.1 and BQ.1.2.1 strains after six passages. This was due to substitutions D614G, H655Y, and N764K in the coronavirus S protein. The same changes in gene variants Gamma and BA.1 were caused by the substitution R682W, which is not present in lineages CH.1.1 and BQ.1.2.1. A similar substitution, namely R682P, was observed in the BA.5.1 strain. We characterized BA.1 (as a reference), BA.5.2, and XBB.3 strains in vivo as representatives of the main circulating genetic lineages. For the BA.1 strain, ID50 was 1.3 and 14 TCD50 in Syrian hamsters and BALB/c mice, respectively. An insignificant increase in the BA.5.2 virulence compared to that of BA.1 was noted (ID50 was 07. and 10 TCD50, respectively). The XBB.3 pathogenicity in laboratory animals is similar to that of BA.1 (ID50 was 1.8 and 15 TCD50, respectively). Experiments showed a consistent decrease in the virulence of Omicron strains compared to previously circulating SARS-CoV-2 variants. A co-evolutionary change in amino acid sequences, affecting the conformation of the coronavirus S protein and its surface epitopes in representatives of different genetic lineages, was noted. The emergence of potential proteolysis sites and alterations of the furin cleavage site have been observed in numerous Omicron coronavirus variants.

SARS-CoV-2 continues to widely circulate in populations globally. Underdetection is acknowledged and is problematic when attempting to capture the true prevalence. Seroprevalence studies, where blood samples from a population sample are tested for SARS-CoV-2 antibodies that react to the SARS-CoV-2 virus, are a common method for estimating the proportion of people previously infected with the virus in a given population. However, obtaining reliable estimates from seroprevalence studies is challenging for a number of reasons, and the uncertainty in the results is often overlooked by scientists, policy makers and the media. This paper reviews the methodological issues that arise in designing these studies, and the main sources of uncertainty that affect the results. We discuss the choice of study population, recruitment of subjects, uncertainty surrounding the accuracy of antibody tests themselves, and the relationship between antibodies and infection over time. Understanding these issues can help the reader to interpret and critically evaluate the results of seroprevalence studies.

The world is facing a major health crisis, the global pandemic of COVID-19 caused by the SARS-CoV-2 coronavirus, for which no approved antiviral agents or vaccines are currently available. Here we describe a collection of codon-optimized coding sequences for SARS-CoV-2 cloned into Gateway-compatible entry vectors, which enable rapid transfer into a variety of expression and tagging vectors. The collection is freely available via Addgene. We hope that widespread availability of this SARS-CoV-2 resource will enable many subsequent molecular studies to better understand the viral life cycle and how to block it.

We review aspects of the antibody response to SARS-CoV-2, the causative agent of the COVID- 19 pandemic. The topics we cover are relevant to immunotherapy with plasma from recovered patients and with monoclonal antibodies against the viral S-protein. The development of vaccines against SARS-CoV-2, an essential public health tool, will also be informed by an understanding of the antibody response in infected patients. Although virus-neutralizing antibodies are likely to protect, antibodies could potentially trigger immunopathogenic events in SARS-CoV-2-infected patients or enhance infection. An awareness of these possibilities may benefit clinicians and the developers of antibody-based therapies and vaccines.

Azithromycin has been shown to have a clinical efficacy against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2); ivermectin has also demonstrated a remarkable experimental efficacy with a potential to be used for Coronavirus disease 2019 (COVID-19). Further, BCG vaccination is being considered for clinical trials aiming to test its potential for lowering COVID-19 morbidity and mortality. This article illustrates some structural and functional relationships that may gather these drugs and the author, basing on a combined pathophysiological and pharmacological approach, recommends the FDA-approved antidiarrhea drug; nitazoxanide, which has been previously suggested but unfortunately ignored, to be tested in combination with azithromycin for their potential activity against SARS CoV-2 soonest. The author recommends testing their combined administration as early during the clinical course of COVID-19 as possible. Further, basing on the same represented concept, the author recommends more trials for interferons to be tested against SARS CoV-2 especially in severe and critical cases.

Recent studies have confirmed that lung microvascular endothelial injury plays a critical role in the pathophysiology of COVID-19. Our group and others have demonstrated the beneficial effects of H2S in several pathological processes and provided a rationale for considering the therapeutic implications of H2S in COVID-19 therapy. Here, we evaluated the effect of the slow-releasing H2S donor, GYY4137, on the barrier function of a lung endothelial cell monolayer in vitro, after challenging the cells with plasma samples from COVID-19 patients or inactivated SARS-CoV-2 virus. We also assessed how the cytokine/chemokine profile of patients’ plasma, endothelial barrier permeability, and disease severity correlated with each other. Alterations of barrier permeability after treatments with patient plasma, inactivated virus, and GYY4137 were monitored and assessed by electrical impedance measurements in real-time. We present evidence that GYY4137 treatment reduced endothelial barrier permeability after plasma challenge and completely reversed the endothelial barrier disruption caused by inactivated SARS-CoV-2 virus. We also showed that disease severity correlated with the cytokine/chemokine profile of the plasma but not with barrier permeability changes in our assay. Overall, these data demonstrate that treatment with H2S-releasing compounds has the potential to ameliorate SARS-CoV-2–associated lung endothelial barrier disruption.

Nowadays, the human population is facing the third and may be the worst pandemic caused by human coronaviruses (CoVs). The virus was first reported in Wuhan, China on 31 December 2019 and spread within short time to almost all countries of the world. Genome analysis of the early virus isolates has revealed high similarity with SARS-CoV and hence the new virus was officially named SARS-CoV-2. Since CoVs have the largest genome among all RNA viruses, they can adapt many point mutation and recombination events; particularly in spike gene, that enable these viruses to rapidly change and evolve in nature. CoVs are known to cross the species boundaries by using different cellular receptors. SARS-CoV-2 is believed to originate in bats and transmitted to human being through an ill-defined intermediate host. In the current review, different aspects of SARS-CoV-2 biology and pathogenicity are discussed including virus genetics and evolution, spike protein and its role in evolution and adaptation to novel hosts, and virus transmission and persistence in nature. In addition, the immune response developed during SARS-CoV-2 infection is demonstrated with special reference to the interplay between immune cells and their role in disease progression. We believe that SARS-CoV-2 outbreak will not be the last and spillover of CoVs from bats will continue. Therefore, establishing intervention approaches to reduce the likelihood of future CoVs spillover from the natural reservoirs is a priority.

With the emergence of the novel corona virus SARS-CoV-2 since December 2019, more than 43 million cases have been reported worldwide. This virus has shown high infectivity and severe symptoms in some cases leading to over 1 million deaths globally. Despite the collaborative and concerted research efforts that has been made, no effective treatment for COVID-19 (corona virus disease-2019) is currently available. SARS-CoV-2 uses the angiotensin converting enzyme 2 (ACE2) as an initial mediator for viral attachment and host cell invasion. ACE2 is widely distributed in human tissues including the cell surface of lung cells which represent the primary site of the infection. Inhibiting or reducing cell surface availability of ACE2 represents a promising therapy for tackling COVID-19. In this context, most ACE2–based therapeutic strategies have aimed to achieve this through the use of angiotensin converting enzyme (ACE) inhibitors or neutralizing the virus by exogenous administration of ACE2. However, through this review, we present another perspective focusing on the subcellular localization and trafficking of ACE2. Membrane targeting of ACE2, shedding and its cellular trafficking pathways including internalization are not well elucidated. Therefore, hereby we present an overview on the fate of newly synthesized ACE2, its post translational modifications, what is known of its trafficking pathways. In addition, we highlight the possibility that some of the identified ACE2 missense variants might affect its trafficking efficiency and localization and hence may explain some of the observed variable severity of SARS-CoV-2 infections. Extensive understanding of these processes is necessary to evaluate the potential use of ACE2 as a credible therapeutic target.

Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analysed by flow cytometry, and IFNγ, IL-6 and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month and 18 years. The majority, 52.8%, had mild disease, and 30.6 % were diagnosed with MIS-C. The main symptoms reported were fever, cough and diarrhoea. A correlation was found between IL-10 and IL-6 concentrations and age group; lymphocyte subpopulations and nutritional status and steroid use; IL-6 concentrations and clinical severity. The results suggest a different immune response depending on age and nutritional status that should be considered for treating pediatric COVID-19 patients.

Coronavirus Disease 2019 (COVID-19) is an infectious respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease, first identified in the Chinese city of Wuhan in November 2019 and has since spread worldwide, is the latest human pandemic, and has officially infected over 800 million people and has caused nearly seven million deaths to date. Although SARS-CoV-2 belongs to the large family of coronaviruses, it has some unique biological characteristics in its interplay with the human host. Therefore, this narrative review aims to provide an up-to-date overview of the structure of the virus, incubation and shedding in the human host, infectivity and biological evolution over time, as well as the main mechanisms for invading human host cells and replicating within. We also proffer that ongoing epidemiological surveillance of newly emerged variants must always be accompanied by biological studies aimed at deciphering new advantageous traits that may contribute to increasing virulence and pathogenicity, such that the most appropriate strategies for establishing a (relatively) safe coexistence with the human host can be implemented.

(1) Background: When the Omicron variant of SARS-CoV-2 first emerged in Germany in January 2022, data on related disease severity among children and adolescents was not yet available. Given Omicron’s high transmissibility, the ability to assess its impact on admission and hospitalization rates in children’s hospitals is critical for the purpose of understanding the scope of its burden on the German health care system. (2) Methods: From January 24, 2022 to July 31, 2022, SARS-CoV-2 cases admitted to German pediatric hospitals were monitored via a national, clinician-led reporting system (CLRS) established by the German Society for Pediatric Infectious Diseases (DGPI). Cases treated on general wards and intensive care units, as well as patient age and need for respiratory support were recorded. (3) Results: From January to July 2022, a median of 1.7 cases (range 0.4–3) per reporting pediatric hospital per day were hospitalized on general wards, whereas a median of 0.1 cases (range 0–0.4 cases) were on intensive care units. Of all hospitalized patients, 4.2% received respiratory support. (4) Conclusions: Despite the high incidence rates documented in connection with the Omicron variant in early 2022, the number of pediatric hospital admissions, and especially the number of cases with need for intensive care treatment and respiratory support due to a symptomatic SARS-CoV-2 infection, remained relatively low. Higher Omicron incidence rates had only a modest impact on SARS-CoV-2-related admissions and hospitalization in German children’s hospitals.

Within the micro and nano world, tiny membrane-enclosed bits of material are more or less free to move and act as communication tools within cells, between cells, between different tissues and between organisms in global environment. Based on the mechanism of membrane budding and vesiculation that includes all types of cells, in this review, we attempted to present a review on SARS-CoV-2 virus actions in compartments of different scales (cells and their surroundings, tissues, organisms and society). Interactions of the virus with cells on a molecular level, with neural system, endothelium, hematopoietic system, gastrointestinal system and genitourinary system. Transmission route between organisms and between mother and fetus are considered. Also, transmission of virus through contact with materials and with environment, the suggested measures to prevent contamination with the virus and to support the organism against the disease are given.

Almost half of the confirmed COVID-19 cases detected so far in the United Kingdom are part of a large cluster of 13 British nationals who tested positive for SARS-CoV-2 in the UK, Spain, and France. Transmissions among this cluster occurred at a ski resort in France, and originated from a single infected traveller returning from a conference in Singapore where he acquired the virus. At least 21 individuals were exposed to the virus, tested, and quarantined, with 13 of those testing positive between the period of 6th Feb and 15th Feb. Here, all publicly available information about the primarily UK/France cluster is consolidated, providing a complete and accessible summary of the cases and their connections. Notable in this cluster are the number of individuals infected, the apparent absence of any severe illness among those infected, and a case of a `delayed positive' test during isolation after initially testing negative, at least 7 days after last possible contact.

The prevalence of corona virus and the novel COVID-19 disease in the entire globe has exacerbated different impact on socioeconomic spectrum in the world, including water use pattern. Thus a research was conducted to examine the comparative use of water during pre- and post-COVID-19 lockdown pattern among post-primary schools in Iwo, Osun State, Nigeria. A survey was conducted among fifteen schools which were randomly selected, but with eight public and seven private schools for the investigation. Both descriptive and inferential statistical techniques were used in data analysis. The results revealed that the major source of water to the schools investigated is ground water which is obtained through hand-dug wells and boreholes. It was further discovered that there was increase in water use during post-COVID-19 lockdown era as a result of the directive by the government that clean water should be provided for hand-washing by all schools regardless of the owner to curtail the spread of COVID-19 disease in the country. One sample t-test also revealed that there was a significant difference in water use at (p<0.01) level. It is recommended that the government and other stakeholders in water sector to ensure that all-time and non-seasonal dependent source of water be provided rather than ground water source which is susceptible to variations in water yields from seasonal variations. This will enable continuous clean water supply, for all purposes, including COVID-19 protocols.

The ongoing COVID-19 pandemic is shaking the foundations of public health governance all over the world. Researchers are challenged by informing and supporting authorities on acquired knowledge and practical implications. This commentary applies established theories of risk perception research to COVID-19 and reflects on the role of risk perceptions in these unprecedented times. Moreover, it calls for utilizing the knowledge on risk perception to improve health risk communication, build trust and contribute to a collaborating governance.

The COVID-19 pandemic has significantly impacted global health and economies, necessitating the development of effective vaccines against the novel virus. Understanding the structure and function of SARS-CoV-2 is crucial for rational vaccine design. The virus consists of several key proteins, including the spike protein, envelope protein, membrane protein, and nucleocapsid protein. The spike protein plays a crucial role in host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2) receptor on human cells. The replication of the virus within host cells is facilitated by various viral proteins, such as the RNA-dependent RNA polymerase (RdRp) and the main protease (Mpro). Rational vaccine design strategies for SARS-CoV-2 primarily focus on targeting the spike protein due to its role in host cell entry. However, developing vaccines against this protein is challenging due to its highly mutable nature and potential conformational changes. Alternative strategies involve using other viral proteins, such as the nucleocapsid protein, which is conserved and essential for viral replication. Considering T-cell responses in vaccine design is also vital as they play a vital role in controlling viral infections. Vaccines that elicit both antibody and T-cell responses are more likely to provide robust and durable immunity against SARS-CoV-2. Advancements in rational vaccine design for SARS-CoV-2 include mRNA-based vaccines, viral vector-based vaccines, and protein subunit vaccines. However, challenges remain in developing a universally effective vaccine, including the emergence of new SARS-CoV-2 variants and mutations that may affect the efficacy of existing vaccines. In conclusion, rational vaccine design for SARS-CoV-2 requires a comprehensive understanding of the virus's structure and function, targeting key viral proteins, and considering T-cell responses.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenges include understanding what triggered SARS-CoV-2 emergence, how this RNA virus is evolving or how the genomic variability may impact the primary structure of proteins that are targets for vaccine. We analyzed 19471 SARS-CoV-2 genomes and 199,984 spike glycoprotein sequences available at the GISAID database from all over the world and 3335 genomes of other Coronoviridae family members available at Genbank, collecting SARS-CoV-2 high-quality genomes and distinct Coronoviridae family genomes. Here, we identify a SARS-CoV-2 emerging cluster containing 13 closely related genomes isolated from bat and pangolin that showed evidence of recombination, which may have contributed to the emergence of SARS-CoV-2. The analyzed SARS-CoV-2 genomes presented 9632 single nucleotide polymorphisms (SNPs) corresponding to a variant density of 0.3 over the genome, and a clear geographic distribution. SNPs are unevenly distributed throughout the genome and hotspots for mutations were found for the spike gene and ORF 1ab. We describe a set of predicted spike protein epitopes whose variability is negligible. All predicted epitopes for the structural E, M and N proteins are highly conserved. This result favors the continuous efficacy of the available vaccines.

Aims: Angiotensin-converting enzyme 2 (ACE2) plays an important role in the entry of coronaviruses into host cells. This paper described how carnosine, a naturally occurring supplement, can be an effective drug candidate for coronavirus disease (COVID-19) on the basis of molecular docking and modeling to host ACE2 co-crystallized with COVID-19 spike protein. Methods: First, the starting point was ACE2 inhibitors and their structure-activity relationship (SAR). Next, chemical similarity (or diversity) and PubMed searches made it possible to repurpose and assess approved or experimental drugs for COVID-19. In parallel, at all stages, authors performed bioactivity scoring to assess potential repurposed inhibitors at ACE2. Finally, investigators performed molecular docking and modeling of the identified drug candidate to host ACE2 co-crystallized with COVID-19 spike protein. Results: Carnosine emerged as the best known drug candidate to match ACE2 inhibitor structure. Preliminary docking was more optimal to ACE2 than the known typical angiotensin-converting enzyme 1 (ACE1) inhibitor (enalapril) and quite comparable to known or presumed ACE2 inhibitors. Viral spike protein elements binding to ACE2 were retained in the best carnosine pose in SwissDock at 1.75 Angstroms. Out of the three main areas of attachment expected to the co-crystallized protein structure, carnosine bind with higher affinity to two compared to the known ACE2 active site. LibDock score was 92.40 for site 3, 90.88 for site 1, and inside the active site 85.49. Conclusion: Carnosine has promising inhibitory interactions with host ACE2 co-crystallized with COVID-19 spike protein and hence could offer potential mitigating effect against current COVID-19 pandemic.

Conservation history of D614 residue is valuable in predicting the consequences of D614G mutation in the SARS-CoV-2 spike glycoprotein (SGP). We report here that the D614 belonged to an extraordinarily conserved, densely hydrophobic eleven amino acid peptide-motif vavlyqdvnct (11-aa), in the Sarbecovirus group and the variant carrying vavlyqdvnct had appeared in Chinese samples and became predominant in several geographical hotspots in late March, 2020. Interestingly a 2009 annotation of SARS-CoV contained the same mutation.

Body mass index has been studied as one of the factors that negatively influences COVID-19. In this work we intend to analyze this influence. A representative sample of the population of Beira Interior was used (around 2%), to which immunity research and a socio-demographic survey were carried out. It was found that obesity influences the vaccination rate, and all other variables analyzed were not influenced by the body mass index.

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.

ACE2 impact on the severity of COVID-19 is widely discussed but still controversial. To estimate its role in aspects of the main risk factors and comorbidities, we involved post-COVID-19 patients in Ternopil region (Ukraine). Recruitment period was July 2020 to December 2021. Medical records, treatment modalities and outcomes were recorded and analyzed. Serum human ACE2 protein was measured with Cusabio ELISA kits (Houston, TX, USA). Statistical analysis was performed with SPSS21.0 software (SPSS Inc., Chicago, IL, USA). The level of ACE2 serum protein was significantly higher (p < 0.001) in patients with mild symptoms compared to more severe course of disease, and inversely had changed from 1 to 90 days after recovery. In patients with mild COVID-19, ACE2 level significantly decreased over time, while among critical patients, it increased by 34.1percent. Such results could be explained by ACE2 shedding from tissues into circulation. Loss of the membrane-bound form of the enzyme decreases the virus entry into cells. Our studies did not identify any sex-related ACE2 serum levels correlation. The most common comorbidities were hypertension, cardiovascular diseases, respiratory diseases and diabetes mellitus. All comorbidities except respiratory diseases contribute to the severity of disease and correlate with ACE2 blood serum level.

ORF7b-2 is an accessory protein of the SARS-CoV-2 virus of only 43 amino acids. It has been implicated in various functional hypotheses, some of which predict its involvement as a trans-membrane protein. In this study, ORF7b-2 has often been compared to ORF7b-1 of the SARS virus to highlight differences and similarities with a protein that should have a similar biological role. Structural analysis of ORF7b-2 and its electrostatic characteristics show a polypeptide with both ends negatively charged and a diffuse negative charge over the entire structure. Therefore, its behavior in solution is like that of a weak negative polyelectrolyte, more precisely a polyanion with a net charge of – 4 at neutral pH. Its structure was modeled with two different modeling systems, one of which was ab initio. The two best models are similar, as confirmed by the Ramachandran plot, and show a central alpha-helical structure with two disordered and mobile ends. A normal mode analysis characterized the low-frequency dynamic aspects of the protein. The analysis of the structural shows a rigid central segment with mobile and fluctuating extremities, involved in a conformational equilibrium of the helix ↔ coil type. The calculation of the dipole moment shows its vector is not aligned with the main axis of the structure with an outward tilt of 24°. Molecular dynamics simulations were also conducted and the one in water is in good agreement with the previous results. While, the simulation performed by inserting a pre-oriented dimer (OMP) into a solvated lipid showed the low tendency of the protein to solvate in the apolar environment of the membrane. ORF7b-2 also shows a widespread distribution of negative surfaces that dynamically adjust to changes in structural organization. The BioGrid platform's [Biological General Repository for Interaction Datasets] through the BioGrid COVID-19 Coronavirus Curation Project shows a very large number of experimentally proven physical interactions unique to ORF7b-2, some of them with cytoplasmic proteins. These features of ORF7b-2, evaluated together, suggest a remarkable propensity of ORF7b-2 to interact with multiple molecular partners on both an electrostatic and hydrophobic basis. All this makes it unreasonable that the only biological function of this protein should be that exerted as an intramembrane protein.

As reported by us and others previously (1, 2), the D614G mutation appeared in the spike glycoprotein (SPG) of the SARS-CoV-2 (the pathogen behind COVID-19) at the early stages of the pandemic and then G614 containing variant of SARS-CoV-2 became the predominant strain in most human populations across the world. However, one of the most recent reports from India (3) stated the incidence of G614 to be only 26% in the Indian population. This report is contradictory to the information available through the GenBank (4) SARS-CoV-2 sequence deposits made by various laboratories from India. The above stated report currently circulating in the Indian media is likely to create a public perception that the Indian strain is less contagious and such a notion could be harmful to people’s welfare. In view of this concern we have re-evaluated, updated and recalculated the incidence of the G614 variant in the Indian population by analyzing 395 Indian SARS-CoV-2 genomic sequences available in the GenBank as of June 26, 2020. In our analysis we have categorized the samples by the month in which the samples were collected. We have used an alignment-free software tool named Compare (5, 6), and the Basic Local Alignment Search Tool (BLAST) (7) in the present analysis. We finally inspected each of the 395 sequences physically for the presence of aspartic acid (D) or glycine (G) at the 614^th position of the spike glycoprotein. We analyzed an Australian cohort in parallel for comparison. We have found that the prevalence of G614 variant in the Indian samples for the month of June 2020 is 90.6%. The trends are similar with the Australian samples.

Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. 29.8% had no SARS-CoV-2 serologic markers and displayed significantly lower CD4 counts and HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG (0.0003), anti-S IgA (p &lt; 0.0001) and lack of neutralizing activity against Omicron variant (p &lt; 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immunity, but retained cellular immune.

The unprecedented growth of publicly available SARS-CoV-2 genome sequence data has increased demand for effective and accessible SARS-CoV-2 data analysis and visualization tools. A majority of the currently available tools either require computational expertise to deploy or limit user input to pre-selected subsets of SARS-CoV-2 genomes. To address these limitations, we developed ViralVar, a publicly available, point-and-click webtool that gives users the freedom to investigate and visualize user-selected subsets of SARS-CoV-2 genomes obtained from the GISAID public database. ViralVar has two primary features that enable: 1) visualization of spatiotemporal dynamics of SARS-CoV-2 lineages, and 2) structural/functional analysis of genomic mutations. As proof-of-principle, ViralVar was used to explore the evolution of the SARS-CoV-2 pandemic in the USA in the pediatric, adult, and elderly population (n > 1.7 million genomes). While the spatiotemporal dynamics of variants did not differ between these age groups, several USA-specific sublineages arose relative to the rest of the world. Our development and utilization of ViralVar to provide insights on the evolution of SARS-CoV-2 in the USA demonstrates the importance of developing accessible tools to facilitate and accelerate large-scale surveillance of circulating pathogens. The ViralVar webserver is freely available at http://viralvar.org/.

In this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of “Warp Speed” immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the “Warp Speed” vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.

To assess the efficacy of washing cloth masks, we simulated SARS-CoV-2 contamination in tricoline fabric and tested decontaminants to reduce viral particles. Viral suspensions using two variants (B.1.1.28 and P.1) were inoculated in these fabrics, and the inactivation kinetics were evaluated after washing with various household disinfection products (Soap powder, Lysoform®, Hypochlorite sodium and 70% Alcohol), rinse numbers, and exposure times. Afterward, the fabrics were washed in sterile water, viral RNA extracted and amplified using RT-qPCR. Finally, viral replication in cell cultures was examined. Our findings show that all biocidal treatments successfully disinfected the tissue tested. Some products showed less reduction in viral loads, Soap powder (1.60 x 104, 1.04 x 103), Soap powder and Lysoform® (1.60 x 104, 1.04 x 103) and Alcohol 70% (1.02 x 103, 5.91 x 101) respectively. However, when sodium hypochlorite was used, this reduction was significantly increased (viral inactivation in 100% of the washes). After the first wash, the reduction of viral particles was greater for the P.1 variant than for the B.1.1.28 variant (W = 51759, p 0.05). In conclusion the sodium hypochlorite role on cloth masks disinfection may also have implications for future health emergencies as well as recommended by WHO.

With increasing fatalities, the COVID-19 pandemic constitutes a formidable global health challenge. The causative agent, SARS-CoV-2 constantly tests the efficacy of the immune system of its victims. The protective ability of the innate immune system as the first responder largely determines the progression of disease and its clinical prognosis. Evidence suggests that mortalities associated with COVID-19 are largely due to hyperinflammation and a dysregulated immune response. Consequently, the degree of the release of pro-inflammatory cytokines such as IL1, IL-6, and TNF alpha remarkably distinguishes between mild and severe cases of COVID-19. The early prediction of a cytokine storm is made possible by several serum chemistry and hematological markers. The prompt use of these markers for laboratory tests, and the aggressive prevention and management of a cytokine release syndrome is critical in determining the level of morbidity and fatality associated with COVID-19. With respect to the SARS-CoV-2 and the host cell, this literature review focuses on the dynamics of the COVID-19 disease highlighting on the pathogenesis, and the markers of Cytokine Storm. It also proffers solutions by critically looking at the current and potential pharmacological agents that are or can be used to mitigate and manage cytokine storms.

Although rRT-PCR is the gold standard method for SARS-CoV-2 detection, some factors, such as amplification inhibitors presence, lead to false-negative results. Here we describe differences between rRT-PCR results for SARS-CoV-2 infection in normal and diluted samples, simulating the need for dilution due to amplification inhibitors presence. Viral RNA extraction of nasopharyngeal swabs samples from 20 patients previously detected as 'Negative' and 21 patients detected as 'Positive' for SARS-CoV-2 was realized with the EasyExtract DNA-RNA (Interprise®). rRT-PCR was realized with OneStep/COVID-19 (IBMP) kit with normal and diluted (80µl of H₂O RNAse free) samples, totaling 82 tests. The results indicate that there is an average variation (ɑ < 0.05) delaying Cq between the amplification results of internal control (IC), N Gene (NG), and ORF-1ab (OF) of 1.811 Cq, 3.840 Cq, and 3.842 Cq, respectively. The extraction kit does not completely purify the inhibitor compounds, therefore non-amplification by inhibitors may occur. In this study, we obtained a 19.04% false-negative diagnosis after sample dilution, and this process reduces the efficiency of rRT-PCR to 29.80% for detecting SARS-CoV-2. Knowing the rRT-PCR standards of diluted samples can help in the identification of false-negative cases, and consequently avoid a wrong diagnosis.

Results from an explorative study revealing spatio-temporal patterns of the SARS-CoV-2/COVID-19 epidemic in Germany are presented. We dispense with contestable model assumptions and show the intrinsic spatio-temporal patterns of the epidemic dynamics. The analysis is based on COVID-19 incidence data, which are age-stratified and spatially resolved at the county level, provided by the Federal Government’s Public Health Institute of Germany (RKI) for public use. Although the 400 county-related incidence time series show enormous heterogeneity both with respect to temporal features as well as spatial distributions, the counties’ incidence curves organise into well distinguished clusters that coincide with East and West Germany. The analysis is based on dimensionality reduction, multidimensional scaling, network analysis, and diversity measures. Dynamical changes are captured by means of difference-in-difference methods which are related to fold changes of the effective reproduction numbers. The age-related dynamical patterns suggest a considerably stronger impact of children, adolescents and seniors on the epidemic activity than previously expected. Besides these concrete interpretations, the work mainly aims at providing an atlas for spatio-temporal patterns of the epidemic which serves as a basis to be further explored with the expertise from different disciplines, particularly sociology and policy makers. The study should also be understood as a methodological contribution to getting a handle on the unusual complexity of the COVID-19 pandemic.

Evolution of SARS-CoV-2 has followed similar trends as other RNA viruses, e.g., HIV-1 and influenza A. Rapid initial diversification was followed by strong competition and rapid succession of dominant variants. Host-initiated RNA editing has been the primary mechanism for introducing mutations. A significant number of mutations were detrimental and were quickly purged. Fixed mutations are mostly diversifying mutations selected for host adaptation and immune evasion, with the latter accounting for more of the changes. However, immune evasion often comes at the cost of functionality, so that optimal functionality is still far from being accomplished. Instead, selection for antibody-escaping variants and accumulation of near-neutral mutations has led to suboptimal codon usage and reduced replicative capacity as demonstrated in non-respiratory cell lines. Beneficial adaptation of the virus includes reduced infectivity in lung tissues and increased tropism for the upper airway, resulting in shorter incubation periods, milder diseases, and more efficient transmission between people.

The ongoing pandemic of the 2019 novel coronavirus disease (COVID-19) raises a global health crisis, which has resulted in 75,778 confirmed cases with 2130 deaths in China and beyond. Atypical symptom renders it challenging to earlier recognize the 2019-nCoV carrier with the potential ability of equivalent transmission. Therefore, it is needed to gain full spectrum of COVID-19. Here we report clustered COVID-19 cases of person-to-person transmission. The symptoms of typical pneumonia are shared by the two familial members, namely son (Patient 1) and father (Patient 2). Unexpectedly, an influenza-like illness (ILI) is also caused in Patient 3 having close contact with Patient 1 at personal dinner party. Combined with clinical and epidemiological study, chest computed tomography (CT) and molecular diagnosis demonstrate that all the three cases tested positive for COVID-19 with distinct symptoms by human-to-human transmission. To the best of knowledge, it closes in part (if not all), a missing gap of clinical repertoires of COVID-19 outbreaks and underlines the possibility that neglection of cryptic/asymptomatic/mild cold-like syndromes gives biased screen in the earlier stage of COVID-19 cases.

In this report, we demonstrate that it is possible to design epitope-based peptide vaccine candidates to counteract the novel China coronavirus (2019-nCoV) by using an approach similar to the one used in cancer neoantigen vaccination therapy. We identified multiepitope peptide vaccine candidates against 2019-nCov that can potentially trigger both CD4⁺ and CD8⁺ T cell immune response with increased efficiency due to the presence of CD4⁺ and CD8⁺ T cell epitopes and a cathepsin-sensitive linker. Furthermore, we suggest that the peptide design strategy should incorporate population-specific HLA alleles in order to optimize binding specificity of the peptides. We refer to this as populationalized vaccinomics.

To elucidate the cellular immune response to coronavirus disease (COVID-19) among children, we assessed cellular immunity in 8 children post-vaccination for COVID-19 and 11 children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, using the T-SPOT®.COVID assay for both the spike (S) and nucleocapsid (N) proteins. In the vaccinated group, the T-SPOT®.COVID assay for the S protein yielded positive results in all eight children. In contrast, in the post-infection group, the assay for the N protein was positive in 5 of 11 children, with 3 of these 5 children requiring hospital admission, including 2 who needed mechanical ventilation. Therefore, the T-SPOT®.COVID assay is valuable for assessing cellular immunity against COVID-19, and most children infected with COVID-19 may not develop such immunity unless the disease severity is significant.

Background: Repeated SARS-CoV-2 infections are plausible and related published data are scarce. We aimed to identify factors associated with the risk of recurrent (three episodes) laboratory-confirmed symptomatic SARS-CoV-2 infections. Methods: A retrospective cohort study was conducted and 1,700 healthcare workers were enrolled. We used risk ratios (RR) and 95% confidence intervals (CI) to evaluate factors associated with symptomatic SARS-CoV-2 infections. Results: We identified 14 participants with recurrent illness episodes. Therefore, the incidence rate was 8.5 per 10,000 person-months. In multiple model, vaccinated adults (vs. unvaccinated, RR = 1.05 [1.03 - 1.06]) and those with a severe first illness episode (vs mild disease, RR = 1.05 [1.01 - 1.10]) were at increased risk for repeated symptomatic SARS-CoV-2 reinfections. Increasing age showed a protective effect (per each additional year of age: RR = 0.98 [0.97 - 0.99]). Conclusions: Our results suggest that recurrent SARS-CoV-2 infections are rare events in adults and they seem to be determined, partially, by vaccination status and age.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known globally as COVID-19, originated in December 2019 in Wuhan, Hubei province in China and has rapidly spread across the globe ever since. The first recorded case in sub-Saharan Africa was in Nigeria, on the 25th February, 2020. The virus continues to spread, and new variants of the disease have emerged, the number of deaths and new infections in the countries of sub-Saharan Africa has been relatively low compared to predictive models. This could be due to several factors, such as slower transmission dynamics of the virus, a lower-case fatality rate, or a lack of testing or reliable data. Whilst this may also, in part, be due to the robustness of the nations' public health responses, there is scarce reporting on the specifics of this. However, emerging research has demonstrated that various environmental factors could influence virus transmission. The study adopted collected meteorological data that was critically analysed and discussed. The impact of three factors in the context of sub-Saharan African nations: temperature, ultraviolet (UV) exposure and pre-existing infection with Plasmodium (malaria) were discussed. These factors were discussed critically in light of the reduced rates of transmission and mortality observed.

The SARS-CoV-2 pandemic has resulted in the generation of evolutionary-related variants. The S-protein of the B.1.1.7 variant (deletion N-terminal domain (NTD) His69Val70Tyr144) may contribute to altered infectivity. These mutations may have been presaged by animal mutations in minks housed in mink farms that according to the present analysis by modelling of protein ligand docking altered a high affinity binding site in the S-protein NTD. These mutants likely occurred only sporadically in humans. Tissue-adaptations and the size of the mink relative to the infected human population size back then may have comparatively increased the relative mutation rate. Simple, multi-threaded automated docking that is widely available, assigns increased binding of the blood type II A antigen to the SARS-Cov-2 S-protein NTD of B.1.1.7 with an overall increased docking interaction of blood group A harbouring glycolipids relative to group B or H (H, p=0.04). The top scoring glycan is identified as a DSGG (also classified as sialosyl-MSGG or disialosyl-Gb5) that may compete with heparin, which is similar to heparan sulfate linked to proteinaceous receptors on the tissue surface. Other glycolipids are found to interact with lower affinity, except long ligands that have suitable ligand binding poses to match the curved binding pocket.