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The rapid spread of the SARS-CoV-2 Variant of Concern (VOC) Gamma in Amazonas during early 2021 fueled a second large COVID-19 epidemic wave and raised concern about the potential role of reinfections. Very few cases of reinfection associated with the VOC Gamma have been reported to date, and their potential impact on clinical, immunological, and virological parameters remains largely unexplored. Here we describe 25 cases of SARS-CoV-2 reinfection in Brazil. SARS-CoV-2 genomic analysis confirmed that individuals were primo-infected with distinct viral lineages between March and December 2020 (B.1.1, B.1.1.28, B.1.1.33, B.1.195, and P.2) and reinfected with the VOC Gamma between 3 to 12 months after primo-infection. We found a similar mean cycle threshold (Ct) value and limited intra-host viral diversity in both primo-infection and reinfection samples. Sera of 14 patients tested 10-75 days after reinfection displayed detectable neutralizing antibodies (NAb) titers against SARS-CoV-2 variants that circulated before (B.1.*), during (Gamma), and after (Delta and Omicron) the second epidemic wave in Brazil. All individuals had milder or no symptoms after reinfection, and none required hospitalization. These findings demonstrate that individuals reinfected with the VOC Gamma may display relatively high RNA viral loads at the upper respiratory tract after reinfection, thus contributing to onward viral transmissions. Despite this, our study points to a low overall risk of severe Gamma reinfections, supporting that the abrupt increase in hospital admissions and deaths observed in Amazonas and other Brazilian states during the Gamma wave was mostly driven by primary infections. Our findings also indicate that most individuals analyzed developed a high anti-SARS-CoV-2 NAb response after reinfection that may provide some protection against reinfection or disease by different SARS-CoV-2 variants., (© 2023. The Author(s).)

The SARS-CoV-2 variants of concern (VOCs) Delta and Omicron spread globally during mid and late 2021, respectively. In this study, we compare the dissemination dynamics of these VOCs in the Amazonas state, one of Brazil's most heavily affected regions. We sequenced the virus genome from 4128 patients collected in Amazonas between July 1st, 2021, and January 31st, 2022, and investigated the viral dynamics using a phylodynamic approach. The VOCs Delta and Omicron BA.1 displayed similar patterns of phylogeographic spread but different epidemic dynamics. The replacement of Gamma by Delta was gradual and occurred without an upsurge of COVID-19 cases, while the rise of Omicron BA.1 was extremely fast and fueled a sharp increase in cases. Thus, the dissemination dynamics and population-level impact of new SARS-CoV-2 variants introduced in the Amazonian population after mid-2021, a setting with high levels of acquired immunity, greatly vary according to their viral phenotype., (© 2023. The Author(s).)

The coronavirus disease COVID-19 has been the cause of millions of deaths worldwide. Among the SARS-CoV-2 proteins, the non-structural protein 1 (NSP1) has great importance during the virus infection process and is present in both alpha and beta-CoVs. Therefore, monitoring of NSP1 polymorphisms is crucial in order to understand their role during infection and virus-induced pathogenicity. Herein, we analyzed how mutations detected in the circulating SARS-CoV-2 in the population of the city of Manaus, Amazonas state, Brazil could modify the tertiary structure of the NSP1 protein. Three mutations were detected in the SARS-CoV-2 NSP1 gene: deletion of the amino acids KSF from positions 141 to 143 (delKSF), SARS-CoV-2, lineage B.1.195; and two substitutions, R29H and R43C, SARS-CoV-2 lineage B.1.1.28 and B.1.1.33, respectively. The delKSF was found in 47 samples, whereas R29H and R43C were found in two samples, one for each mutation. The NSP1 structures carrying the mutations R43C and R29H on the N-terminal portion (e.g. residues 10 to 127) showed minor backbone divergence compared to the Wuhan model. However, the NSP1 C-terminal region (residues 145 to 180) was severely affected in the delKSF and R29H mutants. The intermediate variable region (residues 144 to 148) leads to changes in the C-terminal region, particularly in the delKSF structure. New investigations must be carried out to analyze how these changes affect NSP1 activity during the infection. Our results reinforce the need for continuous genomic surveillance of SARS-CoV-2 to better understand virus evolution and assess the potential impact of the viral mutations on the approved vaccines and future therapies.

The northern state of Amazonas is among the regions in Brazil most heavily affected by the COVID-19 epidemic and has experienced two exponentially growing waves, in early and late 2020. Through a genomic epidemiology study based on 250 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from different Amazonas municipalities sampled between March 2020 and January 2021, we reveal that the first exponential growth phase was driven mostly by the dissemination of lineage B.1.195, which was gradually replaced by lineage B.1.1.28 between May and June 2020. The second wave coincides with the emergence of the variant of concern (VOC) P.1, which evolved from a local B.1.1.28 clade in late November 2020 and replaced the parental lineage in <2 months. Our findings support the conclusion that successive lineage replacements in Amazonas were driven by a complex combination of variable levels of social distancing measures and the emergence of a more transmissible VOC P.1 virus. These data provide insights to understanding the mechanisms underlying the COVID-19 epidemic waves and the risk of dissemination of SARS-CoV-2 VOC P.1 in Brazil and, potentially, worldwide., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Aims: The aim of this study is to develop a novel antiviral strategy capable of efficiently targeting a broad set of SARS-CoV-2 variants., Background: Since the first emergence of SARS-CoV-2, it has rapidly transformed into a global pandemic, posing an unprecedented threat to public health. SARS-CoV-2 is prone to mutation and continues to evolve, leading to the emergence of new variants capable of escaping immune protection achieved due to previous SARS-CoV-2 infections or by vaccination., Objective: RNA interference (RNAi) is a remarkable biological mechanism that can induce gene silencing by targeting complementary mRNA and inhibiting its translation., Methods: In this study, using the computational approach, we predicted the most efficient siRNA capable of inhibiting SARS-CoV-2 variants of concern (VoCs)., Results: The presented siRNA was characterized and evaluated for its thermodynamic properties, offsite-target hits, and in silico validation by molecular docking and molecular dynamics simulations (MD) with Human AGO2 protein., Conclusion: The study contributes to the possibility of designing and developing an effective response strategy against existing variants of concerns and preventing further., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects various mammalian species, with farmed minks experiencing the highest number of outbreaks. In Spain, we analyzed 67 whole genome sequences and eight spike sequences from 18 outbreaks, identifying four distinct lineages: B.1, B.1.177, B.1.1.7, and AY.98.1. The potential risk of transmission to humans raises crucial questions about mutation accumulation and its impact on viral fitness. Sequencing revealed numerous not-lineage-defining mutations, suggesting a cumulative mutation process during the outbreaks. We observed that the outbreaks were predominantly associated with different groups of mutations rather than specific lineages. This clustering pattern by the outbreaks could be attributed to the rapid accumulation of mutations, particularly in the ORF1a polyprotein and in the spike protein. Notably, the mutations G37E in NSP9, a potential host marker, and S486L in NSP13 were detected. Spike protein mutations may enhance SARS-CoV-2 adaptability by influencing trimer stability and binding to mink receptors. These findings provide valuable insights into mink coronavirus genetics, highlighting both host markers and viral transmission dynamics within communities. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe epidemiological characteristics and perform SARS-CoV-2 genomic surveillance in the southeastern region of São Paulo State. During the first months of 2022, we compared weekly SARS-CoV-2 infection prevalence considering age, Ct value, and variants' lineages. An increase in the number of SARS-CoV-2-positive cases until the fourth epidemiological week of 2022 was observed. From the fourth epidemiological week onwards, the number of tests for SARS-CoV-2 diagnosis began to decrease, but the number of positive samples for SARS-CoV-2 remained high, reaching its most expressive level with a rate of 60% of infected individual cases. In this period, we observed a progressive increase in SARS-CoV-2 infection within the 0–10 age group throughout the epidemiological weeks, from 2.8% in the first epidemiological week to 9.2% in the eighth epidemiological week of 2022. We further observed significantly higher Ct values within younger patient samples compared to other older age groups. According to lineage assignment, SARS-CoV-2 (BA.1) was the most prevalent (74.5%) in the younger group, followed by BA.1.1 (23%), BA.2 (1.7%), and Delta (1%). Phylogenetic analysis showed that BA.2 sequences clustered together, indicating sustained transmission of this Omicron VOC sub-lineage by that time. Our results suggest the initial dissemination steps of the Omicron's sub-linage BA.2 into the younger group, due to specific genomic features of the detected sequences. These data provide interesting results related to the spread, emergence, and evolution of the Omicron variant in the southeast Brazilian population. [ABSTRACT FROM AUTHOR]

Mutations in the SARS-CoV-2 genome can alter the virus' fitness, leading to the emergence of variants of concern (VOC). In Brazil, the Gamma variant dominated the pandemic in the first half of 2021, and from June onwards, the first cases of Delta infection were documented. Here, we investigate the introduction and dispersal of the Delta variant in the RS state by sequencing 1077 SARS-CoV-2-positive samples from June to October 2021. Of these samples, 34.7% were identified as Gamma and 65.3% as Delta. Notably, 99.2% of Delta sequences were clustered within the 21J lineage, forming a significant Brazilian clade. The estimated clock rate was 5.97 × 10−4 substitutions per site per year. The Delta variant was first reported on 17 June in the Vinhedos Basalto microregion and rapidly spread, accounting for over 70% of cases within nine weeks. Despite this, the number of cases and deaths remained stable, possibly due to vaccination, prior infections, and the continued mandatory mask use. In conclusion, our study provides insights into the Delta variant circulating in the RS state, highlighting the importance of genomic surveillance for monitoring viral evolution, even when the impact of new variants may be less severe in a given region. [ABSTRACT FROM AUTHOR]

The recently derived Hybrid-Incidence Susceptible-Transmissible-Removed (HI-STR) prototype is a deterministic compartment model for epidemics and an alternative to the Susceptible-Infected-Removed (SIR) model. The HI-STR predicts that pathogen transmission depends on host population characteristics including population size, population density and social behaviour common within that population. The HI-STR prototype is applied to the ancestral Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) to show that the original estimates of the Coronavirus Disease 2019 (COVID-19) basic reproduction number R 0 for the United Kingdom (UK) could have been projected onto the individual states of the United States of America (USA) prior to being detected in the USA. The Imperial College London (ICL) group's estimate of R 0 for the UK is projected onto each USA state. The difference between these projections and the ICL's estimates for USA states is either not statistically significant on the paired Student t-test or not epidemiologically significant. The SARS-CoV2 Delta variant's R 0 is also projected from the UK to the USA to prove that projection can be applied to a Variant of Concern (VOC). Projection provides both a localised baseline for evaluating the implementation of an intervention policy and a mechanism for anticipating the impact of a VOC before local manifestation. [ABSTRACT FROM AUTHOR]

The emergence and rapid spread of the SARS-CoV-2 Gamma variant in Brazil have raised concerns about SARS-CoV-2 vaccines' neutralizing capacity and viral load impact. Our study aimed to assess the influence of the CoviShield and CoronaVac vaccines on the Ct-N2 value in the healthcare organization's staff who experienced primary SARS-CoV-2 infection. We examined sixty-three COVID-19 cases reported in the first half of 2021 and identified similar clinical and laboratory characteristics among individuals, regardless of the vaccine they received. Surprisingly, our observations revealed that both CoviShield and CoronaVac vaccines had no impact on viral load or the development and severity of symptoms. These findings suggest a potential reduction in neutralizing response and indicate the need to consider the incorporation of other SARS-CoV-2 vaccines and maintain additional containment measures against SARS-CoV-2, as they remain imperative despite vaccination efforts. [ABSTRACT FROM AUTHOR]

Brazil was hit with four consecutive waves of COVID-19 until 2022 due to the ancestral SARS-CoV-2 (B.1 lineage), followed by the emergence of variants/subvariants. Relative risks of adverse outcomes for COVID-19 patients hospitalized during the four waves were evaluated. Data were extracted from the largest Brazilian database (SIVEP-Gripe), and COVID-19 patients who were hospitalized during the peak of each of the four waves (15-week intervals) were included in this study. The outcomes of in-hospital death, invasive (IMV) and non-invasive (NIV) ventilation requirements, and intensive care unit (ICU) admission were analyzed to estimate the relative risks. A higher risk of in-hospital death was found during the second wave for all age groups, but a significant reduction was observed in the risk of death for the elderly during the third and fourth waves compared to patients in the first wave. There was an increased risk of IMV requirement and ICU admissions during the second wave for patients aged 18–59 years old compared to the first wave. Relative risk analysis showed that booster-vaccinated individuals have lower risks of in-hospital death and IMV requirement in all age groups compared to unvaccinated/partially vaccinated patients, demonstrating the relevance of full/booster vaccination in reducing adverse outcomes for patients who were hospitalized during the variant prevalence. [ABSTRACT FROM AUTHOR]

We measured anti-SARS-CoV-2 antibody responses before and after CoronaVac (inactivated) vaccination in a case–control study performed in CoronaVac-immunized individuals participating in a longitudinal prospective study of adults in Manaus (DETECTCoV-19). Antibody responses were measured by standard serological immunoassays. Peak anti-S-RBD and neutralizing RBD-ACE2 blocking antibody responses after two doses of CoronaVac vaccine were similar in vaccine breakthrough cases (n = 9) and matched controls (n = 45). Individuals with hybrid immunity resulting from prior SARS-CoV-2 infection followed by vaccination (n = 22) had elevated levels of anti-N, anti-S-RBD and RBD-ACE2 blocking antibodies after the second vaccine dose compared to infection-naïve individuals (n = 48). Post-vaccination SARS-CoV-2-specific antibody responses rapidly waned in infection-naïve individuals. Antibody responses wane after vaccination, making individuals susceptible to infection by SARS-CoV-2 variants. These findings support the need for booster doses after primary vaccination. Population antibody serosurveys provide critical information toward implementing optimal timing of booster doses. [ABSTRACT FROM AUTHOR]

Genomic surveillance has emerged as a crucial tool in monitoring and understanding the dynamics of viral variants during the COVID-19 pandemic. In the Midwest region of Brazil, Mato Grosso do Sul has faced a significant burden from the SARS-CoV-2 epidemic, with a total of 613,000 confirmed cases as of June 2023. In collaboration with the Central Public Health Laboratory in the capital city of Campo Grande, we conducted a portable whole-genome sequencing and phylodynamic analysis to investigate the circulation of the Omicron variant in the region. The study aimed to uncover the genomic landscape and provide valuable insights into the prevalence and transmission patterns of this highly transmissible variant. Our findings revealed an increase in the number of cases within the region during 2022, followed by a gradual decline as a result of the successful impact of the vaccination program together with the capacity of this unpredictable and very transmissible variant to quickly affect the proportion of susceptible population. Genomic data indicated multiple introduction events, suggesting that human mobility played a differential role in the variant's dispersion dynamics throughout the state. These findings emphasize the significance of implementing public health interventions to mitigate further spread and highlight the powerful role of genomic monitoring in promptly tracking and uncovering the circulation of viral strains. Together those results underscore the importance of proactive surveillance, rapid genomic sequencing, and data sharing to facilitate timely public health responses. [ABSTRACT FROM AUTHOR]

The continuous emergence of novel viruses and their diseases are a threat to global public health as there have been three outbreaks of coronaviruses that are highly pathogenic to humans in the span of the last two decades, severe acute respiratory syndrome (SARS)-CoV in 2002, Middle East respiratory syndrome (MERS)-CoV in 2012, and novel SARS-CoV-2 which emerged in 2019. The unprecedented spread of SARS-CoV-2 worldwide has given rise to multiple SARS-CoV-2 variants that have either altered transmissibility, infectivity, or immune escaping ability, causing diseases in a broad range of animals including human and non-human hosts such as companion, farm, zoo, or wild animals. In this review, we have discussed the recent SARS-CoV-2 outbreak, potential animal reservoirs, and natural infections in companion and farm animals, with a particular focus on SARS-CoV-2 variants. The expeditious development of COVID-19 vaccines and the advancements in antiviral therapeutics have contained the COVID-19 pandemic to some extent; however, extensive research and surveillance concerning viral epidemiology, animal transmission, variants, or seroprevalence in diverse hosts are essential for the future eradication of COVID-19. [ABSTRACT FROM AUTHOR]

The main objective of this study was to investigate the dynamic of SARS-CoV-2 viral excretion in rectal swab (RS), saliva, and nasopharyngeal swab (NS) samples from symptomatic patients and asymptomatic contacts. In addition, in order to evaluate the replication potential of SARS-CoV-2 in the gastrointestinal (GI) tract and the excretion of infectious SARS-CoV-2 from feces, we investigated the presence of subgenomic nucleoprotein gene (N) mRNA (sgN) in RS samples and cytopathic effects in Vero cell culture. A prospective cohort study was performed to collect samples from symptomatic patients and contacts in Rio de Janeiro, Brazil, from May to October 2020. One hundred and seventy-six patients had samples collected at home visits and/or during the follow up, resulting in a total of 1633 RS, saliva, or NS samples. SARS-CoV-2 RNA was detected in 130 (73.9%) patients who had at least one sample that tested positive for SARS-CoV-2. The presence of replicating SARS-CoV-2 in RS samples, measured by the detection of sgN mRNA, was successfully achieved in 19.4% (6/31) of samples, whilst infectious SARS-CoV-2, measured by the generation of cytopathic effects in cell culture, was identified in only one RS sample. Although rare, our results demonstrated the replication capacity of SARS-CoV-2 in the GI tract, and infectious viruses in one RS sample. There is still a gap in the knowledge regarding SARS-CoV-2 fecal–oral transmission. Additional studies are warranted to investigate fecal or wastewater exposure as a risk factor for transmission in human populations. [ABSTRACT FROM AUTHOR]

The introduction of SARS-CoV-2 variants of concern (VOCs) in Brazil has been associated with major impacts on the epidemiological and public health scenario. In this study, 291,571 samples were investigated for SARS-CoV-2 variants from August 2021 to March 2022 (the highest peak of positive cases) in four geographical regions of Brazil. To identify the frequency, introduction, and dispersion of SARS-CoV-2 variants in 12 Brazilian capitals, VOCs defining spike mutations were identified in 35,735 samples through genotyping and viral genome sequencing. Omicron VOC was detected in late November 2021 and replaced the Delta VOC in approximately 3.5 weeks. We estimated viral load differences between SARS-CoV-2 Delta and Omicron through the evaluation of the RT-qPCR cycle threshold (Ct) score in 77,262 samples. The analysis demonstrated that the Omicron VOC has a lower viral load in infected patients than the Delta VOC. Analyses of clinical outcomes in 17,586 patients across the country indicated that individuals infected with Omicron were less likely to need ventilatory support. The results of our study reinforce the importance of surveillance programs at the national level and showed the introduction and faster dispersion of Omicron over Delta VOC in Brazil without increasing the numbers of severe cases of COVID-19. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious global challenge requiring urgent and permanent therapeutic solutions. These solutions can only be engineered if the patterns and rate of mutations of the virus can be elucidated. Predicting mutations and the structure of proteins based on these mutations have become necessary for early drug and vaccine design purposes in anticipation of future viral mutations. The amino acid composition (AAC) of proteomes and individual viral proteins provide avenues for exploitation since AACs have been previously used to predict structure, shape and evolutionary rates. Herein, the frequency of amino acid residues found in 1637 complete proteomes belonging to 11 SARS-CoV-2 variants/lineages were analyzed. Leucine is the most abundant amino acid residue in the SARS-CoV-2 with an average AAC of 9.658% while tryptophan had the least abundance of 1.11%. The AAC and ranking of lysine and glycine varied in the proteome. For some variants, glycine had higher frequency and AAC than lysine and vice versa in other variants. Tryptophan was also observed to be the most intolerant to mutation in the various proteomes for the variants used. A correlogram revealed a very strong correlation of 0.999992 between B.1.525 (Eta) and B.1.526 (Iota) variants. Furthermore, isoleucine and threonine were observed to have a very strong negative correlation of −0.912, while cysteine and isoleucine had a very strong positive correlation of 0.835 at p < 0.001. Shapiro-Wilk normality test revealed that AAC values for all the amino acid residues except methionine showed no evidence of non-normality at p < 0.05. Thus, AACs of SARS-CoV-2 variants can be predicted using probability and z-scores. AACs may be beneficial in classifying viral strains, predicting viral disease types, members of protein families, protein interactions and for diagnostic purposes. They may also be used as a feature along with other crucial factors in machine-learning based algorithms to predict viral mutations. These mutation-predicting algorithms may help in developing effective therapeutics and vaccines for SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced diverse molecular variants during its recent expansion in humans that caused different transmissibility and severity of the associated disease as well as resistance to monoclonal antibodies and polyclonal sera, among other treatments. In order to understand the causes and consequences of the observed SARS-CoV-2 molecular diversity, a variety of recent studies investigated the molecular evolution of this virus during its expansion in humans. In general, this virus evolves with a moderate rate of evolution, in the order of 10−3–10−4 substitutions per site and per year, which presents continuous fluctuations over time. Despite its origin being frequently associated with recombination events between related coronaviruses, little evidence of recombination was detected, and it was mostly located in the spike coding region. Molecular adaptation is heterogeneous among SARS-CoV-2 genes. Although most of the genes evolved under purifying selection, several genes showed genetic signatures of diversifying selection, including a number of positively selected sites that affect proteins relevant for the virus replication. Here, we review current knowledge about the molecular evolution of SARS-CoV-2 in humans, including the emergence and establishment of variants of concern. We also clarify relationships between the nomenclatures of SARS-CoV-2 lineages. We conclude that the molecular evolution of this virus should be monitored over time for predicting relevant phenotypic consequences and designing future efficient treatments. [ABSTRACT FROM AUTHOR]

The specialized literature emphasizes the fact that vitamin D has a potentially beneficial effect in the context of the current COVID-19 pandemic. The purpose of this article is to highlight the role of vitamin D, both prophylactic and curative, in the treatment of patients diagnosed with COVID-19. Even though its relevance is still unknown and causes various controversies, there is currently no specific treatment for patients diagnosed with COVID-19. There are various prevention strategies with new vaccination schedules, but additional randomized and clinical trials are still needed to combat this pandemic. In addition to the systemic manifestations of SARS-CoV-2 infection, oral manifestations of this disease have also been described in the literature. The etiology of oral manifestations associated with COVID-19 infection and vitamin D deficiency remains controversial. In the present studies, oral manifestations such as salivary gland infections, aphthae, erythema, gingivitis, ulcers, etc. have been reported. This is a new topic, and the prevalence of manifestations is described in only a few studies, which is inconsistent with the number of COVID-19 cases reported since the beginning of the pandemic. The clinical symptomatology in patients with current COVID-19 infection is polymorphic. Whether the oral manifestation is directly caused by SARS-CoV-2 or a secondary manifestation remains an important topic to analyze and discuss. [ABSTRACT FROM AUTHOR]

Several studies have monitored the SARS-CoV-2 variants in Brazil throughout the pandemic. Here, we systematically reviewed and conducted a scientometric analysis of the SARS-CoV-2 genomic surveillance studies using Brazilian samples. A Pubmed database search on October 2022 returned 492 articles, of which 106 were included. Ninety-six different strains were reported, with variant of concern (VOC) gamma (n = 35,398), VOC delta (n = 15,780), and the variant of interest zeta (n = 1983) being the most common. The top three states with the most samples in the published articles were São Paulo, Rio de Janeiro, and Minas Gerais. Whereas the first year of the pandemic presented primary circulation of B.1.1.28 and B.1.1.33 variants, consecutive replacements were observed between them and VOI zeta, VOC gamma, VOC delta, and VOC omicron. VOI mu, VOI lambda, VOC alpha, and VOC beta were also detected but failed to reach significant circulation. Co-infection, re-infection, and vaccine breakthrough reports were found. Article co-citation differed from the co-authorship structure. Despite the limitations, we expect to give an overview of Brazil's genomic surveillance studies and contribute to future research execution. [ABSTRACT FROM AUTHOR]

São Paulo state has been the epicenter of the Coronavirus Disease 2019 (COVID-19) in Brazil, ranking first by state with over six million reported cases. In February 2021, the P.4 lineage was reported in 21 cities across the state by public health authorities due to the L452R mutation. Here, by analyzing 17,304 genome sequences of SARS-CoV-2 sampled between February and August of 2021 in 476 distinct cities in São Paulo, we assess the transmission dynamics of the P.4 lineage and other SARS-CoV-2 variants that were, at the time of the study, co-circulating in the state. Additionally, clinical parameters from the city of Araras, São Paulo (N = 251) were considered to estimate the potential risk and mortality rate associated with the P.4 lineage since its higher prevalence was observed in that city. Our data suggest a low frequency (0.55%) of the P.4 lineage across the state, with the gamma variant being the dominant form in all regions (90%) at that time. Furthermore, no evidence of increased transmissibility and disease severity related to the P.4 lineage was observed. The displacement through the time of different lineages in São Paulo highlights how challenging genomic surveillance appears to track the emergence of new SARS-CoV-2 lineages, which could better guide the implementation of control measures. [ABSTRACT FROM AUTHOR]

A large number of SARS-CoV-2 mutations in a short period of time has driven scientific research related to vaccines, new drugs, and antibodies to combat the new variants of the virus. Herein, we present a web portal containing the structural information, the tridimensional coordinates, and the molecular dynamics trajectories of the SARS-CoV-2 spike protein and its main variants. The Spike Mutants website can serve as a rapid online tool for investigating the impact of novel mutations on virus fitness. Taking into account the high variability of SARS-CoV-2, this application can help the scientific community when prioritizing molecules for experimental assays, thus, accelerating the identification of promising drug candidates for COVID-19 treatment. Below we describe the main features of the platform and illustrate the possible applications for speeding up the drug discovery process and hypothesize new effective strategies to overcome the recurrent mutations in SARS-CoV-2 genome. [ABSTRACT FROM AUTHOR]

A total of 19,973 patients were hospitalized in these hospitals within two weeks of receiving a positive COVID-19 test, and within the first two days of their arrival, 15,404 COVID-19 patients were not receiving intensive respiratory assistance [[118]]. Additionally, the international platform investigators of the REMAP-CAP study looked at the impact of sarilumab on 485 patients with severe COVID-19 pneumonia and compared it to 418 participants in the control group, as well as to 972 patients who were given tocilizumab and 378 patients who were given anakinra [[151]]. An improvement in survival was seen in patients who received tocilizumab, according to the pivotal COVID-19 trial RECOVERY, which examined the impact of the drug in 4116 hospitalized COVID-19 patients [[153]]. The trial involved 314 patients with COVID-19, and the findings showed that treatment with subcutaneous casirivimab and imdevimab antibody combinations vs. the placebo significantly reduced the prevalence of symptomatic COVID-19 over 28 days among asymptomatic SARS-CoV-2 individuals living with infected contact on the same premises [[218]]. In a 199 COVID-19 hospitalized patient randomized clinical trial, the outcomes of 99 patients receiving lopinavir/ritonavir and 100 patients in the control group were compared [[45]]. [Extracted from the article]

Molecular surveillance of the new coronavirus through new genomic sequencing technologies revealed the circulation of important variants of SARS-CoV-2. Sanger sequencing has been useful in identifying important variants of SARS-CoV-2 without the need for whole-genome sequencing. A sequencing protocol was constructed to cover a region of 1000 base pairs, from a 1120 bp product generated after a two-step RT-PCR assay in samples positive for SARS-CoV-2. Consensus sequence construction and mutation identification were performed. Of all 103 samples sequenced, 69 contained relevant variants represented by 20 BA.1, 13 delta, 22 gamma, and 14 zeta, identified between June 2020 and February 2022. All sequences found were aligned with representative sequences of the variants. Using the Sanger sequencing methodology, we were able to develop a more accessible protocol to assist viral surveillance with a more accessible platform. [ABSTRACT FROM AUTHOR]

Siddha medicine is one of the oldest medical systems in the world and is believed to have originated more than 10,000 years ago and is prevalent across ancient Tamil land. It is undeniable that inhibitor preferences rise with increasing solubility in water due to the considerations pertaining to the bioavailability and the ease of which unabsorbed residues can be disposed of. In this study, we showed the phytochemical discrimination of Saussurea costus extracted with water at room temperature as a green extraction procedure. A total of 48 compounds were identified using gas chromatography-mass spectrometry (GC-MS). The fatty acids had a high phytochemical abundance at 73.8%, followed by tannins at 8.2%, carbohydrates at 6.9%, terpenoids at 4.3%, carboxylic acids at 2.5%, hydrocarbons at 2.4%, phenolic compounds at 0.2%, and sterols at 1.5%. Of these compounds, 22 were docked on the active side and on the catalytic dyad of His41 and Cys145 of the main protease of SARS-CoV-2 (Mpro). Eight active inhibitors were carbohydrates, five were fatty acids, three were terpenoids, two were carboxylic acids, one was a tannin, one was a phenolic compound, and one was a sterol. The best inhibitors were 4,8,13-Cyclotetradecatriene-1,3-diol, 1,5,9-trimethyl-12-(1-methylethyl), Andrographolide, and delta.4-Androstene-3.beta.,17.beta.-diol, with a binding affinity that ranged from −6.1 kcal/mol to −6.5 kcal/mol. The inhibitory effect of Saussurea costus of SARS-CoV-2 entry into the cell was studied using a pseudovirus with Spike proteins from the D614G variant and the VOC variants Gamma and Delta. Based on the viral cycle of SARS-CoV-2, our results suggest that the Saussurea costus aqueous extract has no virucidal effect and inhibits the virus in the events after cell entry. Furthermore, the biological activity of the aqueous extract was investigated against HSV-1 virus and two bacterial strains, namely Staphylococcus aureus ATCC BAA 1026 and Escherichia coli ATCC 9637. According to this study, an enormous number of water-soluble inhibitors were identified from Saussurea costus against the Mpro, and this is unprecedented as far as we know. [ABSTRACT FROM AUTHOR]

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, and viral RNA was 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, such as soap powder (1.60 × 104, 1.04 × 103), soap powder and Lysoform® (1.60 × 104, 1.04 × 103), and alcohol 70% (1.02 × 103, 5.91 × 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 in the number of viral particles was greater for the P.1 variant than for the B.1.1.28 variant (W = 51,759, p < 0.05). In conclusion, the role of sodium hypochlorite in cloth mask disinfection may also have implications for future health emergencies as well as recommendation by WHO. [ABSTRACT FROM AUTHOR]

Our effort in SARS-CoV-2 genomic surveillance in Brazil has detected the Alpha Variant of Concern with a predominance higher than 75% in the population of Ilhabela island (São Paulo State) at a time when the Gamma VOC was already predominating the mainland raised concerns for closer surveillance on this island. Therefore, we intensified the surveillance for 24 weeks by generating data from 34% of local positive cases. Our data show that the patterns of VOC predominance dynamics and infection rates were in general distinct from the mainland. We report here the first known case of Alpha predominance in a Brazilian population, a delay greater than 3 months for the Gamma to dominate the previous variants compared to the mainland, and a faster dispersion rate of Gamma and Delta VOCs compared to the mainland. Phylogenetic analysis revealed the SARS-CoV-2 transmission dynamics in Ilhabela were characterized by multiple independent introduction events of Gamma and Delta, with a few events of Alpha introduction, two of them followed by community transmission. This study evidenced the peculiar behavior of SARS-CoV-2 variants in an isolated population and brought to light the importance of specific programs for SARS-CoV-2 genomic surveillance in isolated populations. [ABSTRACT FROM AUTHOR]

Since the start of SARS-CoV-2 pandemic, children aged ≤ 12 years have always been defined as underrepresented in terms of SARS-CoV-2 infections' frequency and severity. By correlating SARS-CoV-2 transmission dynamics with clinical and virological features in 612 SARS-CoV-2 positive patients aged ≤ 12 years, we demonstrated a sizeable circulation of different SARS-CoV-2 lineages over the four pandemic waves in paediatric population, sustained by local transmission chains. Age < 5 years, highest viral load, gamma and delta clades positively influence this local transmission. No correlations between COVID-19 manifestations and lineages or transmission chains are seen, except for a negative correlation between B.1.1.7 and hospitalization. [ABSTRACT FROM AUTHOR]

Over the two years that we have been experiencing the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, our challenges have been the race to develop vaccines and the difficulties in fighting against new variants due to the rapid ability of the virus to evolve. In this sense, different organizations have identified and classified the different variants that have been emerging, distinguishing between variants of concern (VOC), variants of interest (VOI), or variants under monitoring (VUM). The following review aims to describe the latest updates focusing on VOC and already de-escalated variants, as well as to describe the impact these have had on the global situation. Understanding the intrinsic properties of SARS-CoV-2 and its interaction with the immune system and vaccination is essential to make out the underlying mechanisms that have led to the appearance of these variants, helping to determine the next steps for better public management of this pandemic. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that belongs to the coronavirus family and is the cause of coronavirus disease 2019 (COVID-19). As of May 2022, it had caused more than 500 million infections and more than 6 million deaths worldwide. Several vaccines have been produced and tested over the last two years. The SARS-CoV-2 virus, on the other hand, has mutated over time, resulting in genetic variation in the population of circulating variants during the COVID-19 pandemic. It has also shown immune-evading characteristics, suggesting that vaccinations against these variants could be potentially ineffective. The purpose of this review article is to investigate the key variants of concern (VOCs) and mutations of the virus driving the current pandemic, as well as to explore the transmission rates of SARS-CoV-2 VOCs in relation to epidemiological factors and to compare the virus's transmission rate to that of prior coronaviruses. We examined and provided key information on SARS-CoV-2 VOCs in this study, including their transmissibility, infectivity rate, disease severity, affinity for angiotensin-converting enzyme 2 (ACE2) receptors, viral load, reproduction number, vaccination effectiveness, and vaccine breakthrough. [ABSTRACT FROM AUTHOR]

In order to determine the humoral protective response against SARS-CoV-2, the vaccine-induced and naturally induced neutralizing antibodies (NtAbs) responses against SARS-CoV-2 variants circulating in Italy through in vitro live virus neutralization assay were evaluated. A total of 39 SARS-CoV-2 recovered subjects (COVID-19+) and 63 subjects with a two-dose cycle of the BNT16262 vaccine were enrolled. A single serum sample was tested for COVID-19+ at 35–52 days post-positive swab, while vaccinees blood samples were taken at one (V1) and at three months (V3) after administration of the second vaccine dose. Significantly higher NtAb titers were found against B.1 and Alpha in both COVID-19+ and vaccinees, while lower NtAb titers were detected against Delta, Gamma, and Omicron variants. A comparison between groups showed that NtAb titers were significantly higher in both V1 and V3 than in COVID-19+, except against the Omicron variant where no significant difference was found. COVID-19+ showed lower neutralizing titers against all viral variants when compared to the vaccinees. Two-dose vaccination induced a sustained antibody response against each analyzed variant, except for Omicron. The evolution process of SARS-CoV-2, through variants originating from an accumulation of mutations, can erode the neutralizing effectiveness of natural and vaccine-elicited immunity. Therefore, a need for new vaccines should be evaluated to contain the ongoing pandemic. [ABSTRACT FROM AUTHOR]

Since November 2019, SARS-CoV-2 has been a matter of global concern due to its rapid spread, the millions of deaths it caused, and repeated waves of infections. One after another, many variants of this novel virus have come into existence due to its constant mutability, specifically in the spike glycoprotein region. The tally for variants of concern (VOCs), which already include Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2), has increased to five with the latest appearance of Omicron (B.1.1.529). In our study, we examine the effect of the transmissibility and infectious potential of the virus due to various mutations of SARS-CoV-2, especially in the receptor-binding domain (RBD). We discuss the role of genome sequencing in tracing all the mutations and the importance of the R value (reproductive number) to understand the virus spread. We also review the effectiveness of the available vaccines on the variants of concern, as the rapid spread of the newly emergent Omicron variant has raised doubts about the usefulness of the current vaccines. The use of a mixed vaccination strategy has proved to be effective, yet the newer variants, such as Omicron, demand booster doses for the population. Multivalent immunogens could be considered as the plausible solution for conferring protection against potential new mutants of the virus in the future. [ABSTRACT FROM AUTHOR]

COVID-19 is a respiration-related disease caused by SARS-CoV-2 and was identified in China's Wuhan city. More than 223 countries are affected by the disease worldwide. The new variants of the COVID-19 virus are causing problems, from average to life-threatening pneumonia and acute respiratory distress syndrome (ARDS). Presently, there are 170 vaccine candidates, out of which 10 have been approved by the WHO for vaccination, such as Ad26.COV2.S, Pfizer/BioNTech, COVISHIELD, Covovax, Moderna, KoviVac, and some other vaccines to combat the deadly SARS-CoV-2 infection. From all these vaccines, Pfizer/BioNTech and Moderna are showing the highest efficacy against COVID-19. These vaccines are highly efficient against COVID-19 disease, but their potentiality against new variants remains a question. COVID-19 vaccines are highly effective at preventing severe illnesses, hospitalizations, and death. The antibodies elicited by earlier infection or vaccination are the key for possible protection against SARS-CoV-2. The problem has been exacerbated by new information from Africa on the origins of the novel contagious SARS-CoV-2 strain. These new strains occur due to unique mutations in the spike protein, which modify SARS-CoV-2 transmission and infection capabilities, limiting the efficacy of the COVID-19 vaccination. Hence, there is a need to find a potential vaccine against it. [ABSTRACT FROM AUTHOR]

The emergence of new SARS-CoV-2 variants and the replacement of preceding isolates have been observed through B.1.1.7, B.1.351, B.1.617.2, and B.1.1.529 lineages (corresponding to alpha, beta, delta, and omicron variants of concern (VoC), respectively). However, there is still a lack of biological evidence to which extent those VoC differ from the ancestral lineages. By exploiting human airway epithelial cell (HAEC) cultures, which closely resemble the human airway architecture and physiology, we report distinctive SARS-CoV-2 tropism in different respiratory tissues. In general, SARS-CoV-2 VoC predominantly infect and replicate in HAEC better than the progenitor USA-WA1 isolate or the BavPat1 isolate, which contains the D614G mutation, even though there is little to no difference between variants regarding their infectivity (i.e., virion-per-vRNA copy ratio). We also observe differential tissue-specific innate immunity activation between the upper and lower respiratory tissues in the presence of the virus. Our study provides better comprehension of the behavior of the different VoC in this physiologically relevant ex vivo model. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) pandemic has caused immeasurable impacts on the health and socioeconomic system. The real-time identification and characterization of new Variants of Concern (VOCs) are critical to comprehend its emergence and spread worldwide. In this sense, we carried out a national epidemiological surveillance program in Brazil from April to October 2021. Genotyping by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and sequencing were performed to monitor the dynamics and dissemination of VOCs in samples from 15 federative units. Delta VOC was first detected on June 2021 and took sixteen weeks to replace Gamma. To assess the transmissibility potential of Gamma and Delta VOCs, we studied the dynamics of RT-qPCR cycle threshold (Ct) score in the dominance period of each variant. The data suggest that Delta VOC has a higher transmission rate than Gamma VOC. We also compared relevant symptom patterns in individuals infected with both VOCs. The Delta-infected subjects were less likely to have low oxygen saturation or fatigue, altered results on chest computed tomography, and a propensity for altered X-rays. Altogether, we described the replacement of Gamma by Delta, Delta enhanced transmissibility, and differences in symptom presentation. [ABSTRACT FROM AUTHOR]

Tracing the appearance and evolution of virus variants is essential in the management of the COVID-19 pandemic. Here, we focus on SARS-CoV-2 spread in Italian patients by using viral sequences deposited in public databases and a tracing procedure which is used to monitor the evolution of the pandemic and detect the spreading, within the infected population of emergent sub-clades with a potential positive selection. Analyses of a collection of monthly samples focused on Italy highlighted the appearance and evolution of all the main viral sub-trees emerging at the end of the first year of the pandemic. It also identified additional expanding subpopulations which spread during the second year (i.e., 2021). Three-dimensional (3D) modelling of the main amino acid changes in mutated viral proteins, including ORF1ab (nsp3, nsp4, 2'-o-ribose methyltransferase, nsp6, helicase, nsp12 [RdRp]), N, ORF3a, ORF8, and spike proteins, shows the potential of the analysed structural variations to result in epistatic modulation and positive/negative selection pressure. These analyzes will be of importance to the early identification of emerging clades, which can develop into new "variants of concern" (i.e., VOC). These analyses and settings will also help SARS-CoV-2 coronet genomic centers in other countries to trace emerging worldwide variants. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has become a global pandemic disease. SARS-CoV-2 variants have aroused great concern and are expected to continue spreading. Although many countries have promoted roll-out vaccination, the immune barrier has not yet been fully established, indicating that populations remain susceptible to infection. In this review, we summarize the literature on variants of concern and focus on the changes in their transmissibility, pathogenicity, and resistance to the immunity constructed by current vaccines. Furthermore, we analyzed relationships between variants and breakthrough infections, as well as the paradigm of new variants in countries with high vaccination rates. Terminating transmission, continuing to strengthen variant surveillance, and combining nonpharmaceutical intervention measures and vaccines are necessary to control these variants. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 pandemic reverberated, posing health and social hygiene obstacles throughout the globe. Mutant lineages of the virus have concerned scientists because of convergent amino acid alterations, mainly on the viral spike protein. Studies have shown that mutants have diminished activity of neutralizing antibodies and enhanced affinity with its human cell receptor, the ACE2 protein. Methods: Hence, for real-time measuring of the impacts caused by variant strains in such complexes, we implemented E-Volve, a tool designed to model a structure with a list of mutations requested by users and return analyses of the variant protein. As a proof of concept, we scrutinized the spike-antibody and spike-ACE2 complexes formed in the variants of concern, B.1.1.7 (Alpha), B.1.351 (Beta), and P.1 (Gamma), by using contact maps depicting the interactions made amid them, along with heat maps to quantify these major interactions. Results: The results found in this study depict the highly frequent interface changes made by the entire set of mutations, mainly conducted by N501Y and E484K. In the spike-Antibody complex, we have noticed alterations concerning electrostatic surface complementarity, breaching essential sites in the P17 and BD-368-2 antibodies. Alongside, the spike-ACE2 complex has presented new hydrophobic bonds. Discussion: Molecular dynamics simulations followed by Poisson-Boltzmann calculations corroborate the higher complementarity to the receptor and lower to the antibodies for the K417T/E484K/N501Y (Gamma) mutant compared to the wild-type strain, as pointed by E-Volve, as well as an intensification of this effect by changes at the protein conformational equilibrium in solution. A local disorder of the loop a1'/ß1', as well its possible effects on the affinity to the BD-368-2 antibody were also incorporated to the final conclusions after this analysis. Moreover, E-Volve can depict the main alterations in important biological structures, as shown in the SARSCoV-2 complexes, marking a major step in the real-time tracking of the virus mutant lineages. E-Volve is available at http://bioinfo.dcc.ufmg.br/evolve. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Many COVID-19 patients require invasive mechanical ventilation (IMV) while others, even with acute respiratory failure, do not (NIMV). Therefore, we aimed to evaluate serum levels of MMP-7 and molecules related to exhausted T-cells as potential biomarkers to differentiate between IMV and NIMV patients. Methods: 105 patients diagnosed with COVID-19 and confirmed by RT-PCR for SARS-CoV-2 were divided into two groups according to the requirement for IMV. Serum levels of sPD-L1, sPD-L2, sTIM-3, sGal-9 and sMMP-7 were quantified by ELISA and correlated with clinical data. Twelve patients were followed up after eight months to compare the levels of the biomarkers between acute disease and post-COVID-19. Results: IMV patients experienced a lower PaO2/FiO2 (p < 0.0001) and a longer hospital stay (p < 0.0001), and exhibited higher levels of sPD-L1 (p < 0.05), sTIM-3 (p < 0.01) and sMMP-7 (p < 0.0001) when compared with NIMV patients. According to a ROC analysis, sMMP-7 had the highest sensitivity (78%) and specificity (76%) with a cut point of 4.5 ng/mL, followed by sTIM-3 and sPD-L1. Eight months post-COVID-19, IMV patients displayed a significant decrease in the initially high levels of sPD-L1, sTIM-3 and sGal-9, while sPD-L2 was increased, and sMMP-7 was unchanged. Conclusion: Circulating levels of sPD-L1, sTIM-3 and sMMP-7 are potential biomarkers of disease severity to distinguish patients requiring IMV. MMP-7 could also be a marker for the persistence of lung lesions post-COVID-19. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic is driven by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) that emerged in 2019 and quickly spread worldwide. Genomic surveillance has become the gold standard methodology used to monitor and study this fast-spreading virus and its constantly emerging lineages. The current deluge of SARS-CoV-2 genomic data generated worldwide has put additional pressure on the urgent need for streamlined bioinformatics workflows. Here, we describe a workflow developed by our group to process and analyze large-scale SARS-CoV-2 Illumina amplicon sequencing data. This workflow automates all steps of SARS-CoV-2 reference-based genomic analysis: data processing, genome assembly, PANGO lineage assignment, mutation analysis and the screening of intrahost variants. The pipeline is capable of processing a batch of around 100 samples in less than half an hour on a personal laptop or in less than five minutes on a server with 50 threads. The workflow presented here is available through Docker or Singularity images, allowing for implementation on laptops for small-scale analyses or on high processing capacity servers or clusters. Moreover, the low requirements for memory and CPU cores and the standardized results provided by ViralFlow highlight it as a versatile tool for SARS-CoV-2 genomic analysis. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, forensic sciences, on the one hand, contributed to gaining knowledge about different aspects of the pandemic, while on the other hand, forensic professionals were called on to quickly adapt their activities to respond adequately to the changes imposed by the pandemic. This review aims to clarify the state of the art in forensic medicine at the time of COVID-19, discussing the following: the influence of external factors on forensic activities, the impact of autopsy practice on COVID-19 and vice-versa, the persistence of SARS-CoV-2 RNA in post-mortem samples, forensic personnel activities during the SARS-CoV-2 pandemic, the global vaccination program and forensic sciences, forensic undergraduate education during and after the imposed COVID-19 lockdown, and the medico-legal implications in medical malpractice claims during the COVID-19 pandemic. The COVID-19 pandemic has greatly influenced different aspects of human life, and, accordingly, the practical activities of forensic sciences that are defined as multidisciplinary, involving different expertise. Indeed, the activities are very different, including crime scene investigation (CSI), external examination, autopsy, and genetic and toxicological examinations of tissues and/or biological fluids. At the same time, forensic professionals may have direct contact with subjects in life, such as in the case of abuse victims (in some cases involving children), collecting biological samples from suspects, or visiting subjects in the case of physical examinations. In this scenario, forensic professionals are called on to implement methods to prevent the SARS-CoV-2 infection risk, wearing adequate PPE, and working in environments with a reduced risk of infection. Consequently, in the pandemic era, the costs involved for forensic sciences were substantially increased. [ABSTRACT FROM AUTHOR]

Here, we report a first comprehensive genomic analysis of SARS-CoV-2 variants circulating in North African countries, including Algeria, Egypt, Libya, Morocco, Sudan and Tunisia, with respect to genomic clades and mutational patterns. As of December 2021, a total of 1669 high-coverage whole-genome sequences submitted to EpiCoV GISAID database were analyzed to infer clades and mutation annotation compared with the wild-type variant Wuhan-Hu-1. Phylogenetic analysis of SARS-CoV-2 genomes revealed the existence of eleven GISAID clades with GR (variant of the spike protein S-D614G and nucleocapsid protein N-G204R), GH (variant of the ORF3a coding protein ORF3a-Q57H) and GK (variant S-T478K) being the most common with 25.9%, 19.9%, and 19.6%, respectively, followed by their parent clade G (variant S-D614G) (10.3%). Lower prevalence was noted for GRY (variant S-N501Y) (5.1%), S (variant ORF8-L84S) (3.1%) and GV (variant of the ORF3a coding protein NS3-G251V) (2.0%). Interestingly, 1.5% of total genomes were assigned as GRA (Omicron), the newly emerged clade. Across the North African countries, 108 SARS-CoV-2 lineages using the Pangolin assignment were identified, whereby most genomes fell within six major lineages and variants of concern (VOC) including B.1, the Delta variants (AY.X, B.1.617.2), C.36, B.1.1.7 and B.1.1. The effect of mutations in SAR-CoV-2 genomes highlighted similar profiles with D614G spike (S) and ORF1b-P314L variants as the most changes found in 95.3% and 87.9% of total sequences, respectively. In addition, mutations affecting other viral proteins appeared frequently including; N:RG203KR, N:G212V, NSP3:T428I, ORF3a:Q57H, S:N501Y, M:I82T and E:V5F. These findings highlight the importance of genomic surveillance for understanding the SARS-CoV-2 genetic diversity and its spread patterns, leading to a better guiding of public health intervention measures. The know-how analysis of the present work could be implemented worldwide in order to overcome this health crisis through harmonized approaches. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has had a significant global impact, with more than 280,000,000 people infected and 5,400,000 deaths. The use of personal protective equipment and the anti-SARS-CoV-2 vaccination campaigns have reduced infection and death rates worldwide. However, a recent increase in infection rates has been observed associated with the appearance of SARS-CoV-2 variants, including the more recently described lineage B.1.617.2 (Delta variant) and lineage B.1.1.529/BA.1 (Omicron variant). These new variants put the effectiveness of international vaccination at risk, with the appearance of new outbreaks of COVID-19 throughout the world. This emergence of new variants has been due to multiple predisposing factors, including molecular characteristics of the virus, geographic and environmental conditions, and the impact of social determinants of health that favor the genetic diversification of SARS-CoV-2. We present a literature review on the most recent information available on the emergence of new variants of SARS-CoV-2 in the world. We analyzed the biological, geographical, and sociocultural factors that favor the development of these variants. Finally, we evaluate the surveillance strategies for the early detection of new variants and prevent their distribution outside these regions. [ABSTRACT FROM AUTHOR]

The worldwide battle against the SARS-CoV-2 virus rages on, with millions infected and many innocent lives lost. The causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a beta coronavirus that belongs to the Coronaviridae family. Many clinically significant variants have emerged, as the virus's genome is prone to various mutations, leading to antigenic drift and resulting in evasion of host immune recognition. The current variants of concern (VOCs) include B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617/B.1.617.2 (Delta), and P.1 (Gamma). The emerging variants contain various important mutations on the spike protein, leading to deleterious consequences, such as immune invasion and vaccine escape. These adverse effects result in increased transmissibility, morbidity, and mortality and the evasion of detection by existing or currently available diagnostic tests, potentially delaying diagnosis and treatment. This review discusses the key mutations present in the VOC strains and provides insights into how these mutations allow for greater transmissibility and immune evasion than the progenitor strain. Continuous monitoring and surveillance of VOC strains play a vital role in preventing and controlling the virus's spread. [ABSTRACT FROM AUTHOR]

In the present study, we provide a retrospective genomic epidemiology analysis of the SARS-CoV-2 pandemic in the state of Rio de Janeiro, Brazil. We gathered publicly available data from GISAID and sequenced 1927 new genomes sampled periodically from March 2021 to June 2021 from 91 out of the 92 cities of the state. Our results showed that the pandemic was characterized by three different phases driven by a successive replacement of lineages. Interestingly, we noticed that viral supercarriers accounted for the overwhelming majority of the circulating virus (>90%) among symptomatic individuals in the state. Moreover, SARS-CoV-2 genomic surveillance also revealed the emergence and spread of two new variants (P.5 and P.1.2), firstly reported in this study. Our findings provided important lessons learned from the different epidemiological aspects of the SARS-CoV-2 dynamic in Rio de Janeiro. Altogether, this might have a strong potential to shape future decisions aiming to improve public health management and understanding mechanisms underlying virus dispersion. [ABSTRACT FROM AUTHOR]

Uruguay controlled the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein, we analyzed the country-wide genetic diversity of SARS-CoV-2 between November 2020 and April 2021. We identified that the most prevalent viral variant during the first epidemic wave in Uruguay (December 2020–February 2021) was a B.1.1.28 sublineage carrying Spike mutations Q675H + Q677H, now designated as P.6, followed by lineages P.2 and P.7. P.6 probably arose around November 2020, in Montevideo, Uruguay's capital department, and rapidly spread to other departments, with evidence of further local transmission clusters; it also spread sporadically to the USA and Spain. The more efficient dissemination of lineage P.6 with respect to P.2 and P.7 and the presence of mutations (Q675H and Q677H) in the proximity of the key cleavage site at the S1/S2 boundary suggest that P.6 may be more transmissible than other lineages co-circulating in Uruguay. Although P.6 was replaced by the variant of concern (VOC) P.1 as the predominant lineage in Uruguay since April 2021, the monitoring of the concurrent emergence of Q675H + Q677H in VOCs should be of worldwide interest. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 pandemic has involved a severe increase of cases worldwide in a wide range of populations. The aim of the present investigation was to evaluate recent insights about COVID-19 infection in children, infants and pregnant subjects. Methods: a literature overview was performed including clinical trials, in vitro studies, reviews and published guidelines regarding the present paper topic. A descriptive synthesis was performed to evaluate recent insights and the effectiveness of therapies for SARS-CoV-2 infection in children, infants and pregnant subjects. Results: Insufficient data are available regarding the relationship between COVID-19 and the clinical risk of spontaneous abortion and premature foetus death. A decrease in the incidence of COVID-19 could be correlated to a minor expression of ACE2 in childrens' lungs. At present, a modulation of the dose-effect posology for children and infants is necessary. Conclusions: Pregnant vertical transmission has been hypothesised for SARS-CoV-2 infection. Vaccines are necessary to achieve mass immunity for children and also pregnant subjects. [ABSTRACT FROM AUTHOR]

Almost a year after the COVID-19 pandemic had begun, new lineages (B.1.1.7, B.1.351, P.1, and B.1.617.2) associated with enhanced transmissibility, immunity evasion, and mortality were identified in the United Kingdom, South Africa, and Brazil. The previous most prevalent lineages in the state of Rio Grande do Sul (RS, Southern Brazil), B.1.1.28 and B.1.1.33, were rapidly replaced by P.1 and P.2, two B.1.1.28-derived lineages harboring the E484K mutation. To perform a genomic characterization from the metropolitan region of Porto Alegre, we sequenced viral samples to: (i) identify the prevalence of SARS-CoV-2 lineages in the region, the state, and bordering countries/regions; (ii) characterize the mutation spectra; (iii) hypothesize viral dispersal routes by using phylogenetic and phylogeographic approaches. We found that 96.4% of the samples belonged to the P.1 lineage and approximately 20% of them were assigned as the novel P.1.2, a P.1-derived sublineage harboring signature substitutions recently described in other Brazilian states and foreign countries. Moreover, sequences from this study were allocated in distinct branches of the P.1 phylogeny, suggesting multiple introductions in RS and placing this state as a potential diffusion core of P.1-derived clades and the emergence of P.1.2. It is uncertain whether the emergence of P.1.2 and other P.1 clades is related to clinical or epidemiological consequences. However, the clear signs of molecular diversity from the recently introduced P.1 warrant further genomic surveillance. [ABSTRACT FROM AUTHOR]

Novel therapies for the treatment of COVID-19 are continuing to emerge as the SARS-Cov-2 pandemic progresses. PCR remains the standard benchmark for initial diagnosis of COVID-19 infection, while advances in immunological profiling are guiding clinical treatment. The SARS-Cov-2 virus has undergone multiple mutations since its emergence in 2019, resulting in changes in virulence that have impacted on disease severity globally. The emergence of more virulent variants of SARS-Cov-2 remains challenging for effective disease control during this pandemic. Major variants identified to date include B.1.1.7, B.1.351; P.1; B.1.617.2; B.1.427; P.2; P.3; B.1.525; and C.37. Globally, large unvaccinated populations increase the risk of more and more variants arising. With successive waves of COVID-19 emerging, strategies that mitigate against community transmission need to be implemented, including increased vaccination coverage. For treatment, convalescent plasma therapy, successfully deployed during recent Ebola outbreaks and for H1N1 influenza, can increase survival rates and improve host responses to viral challenge. Convalescent plasma is rich with cytokines (IL-1β, IL-2, IL-6, IL-17, and IL-8), CCL2, and TNFα, neutralizing antibodies, and clotting factors essential for the management of SARS-CoV-2 infection. Clinical trials can inform and guide treatment policy, leading to mainstream adoption of convalescent therapy. This review examines the limited number of clinical trials published, to date that have deployed this therapy and explores clinical trials in progress for the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

The recent spreading of new SARS-CoV-2 variants, carrying several mutations in the spike protein, could impact immune protection elicited by natural infection or conferred by vaccination. In this study, we evaluated the neutralizing activity against the viral variants that emerged in the United Kingdom (B.1.1.7), Brazil (P.1), and South Africa (B.1.351) in human serum samples from hospitalized patients infected by SARS-CoV-2 during the first pandemic wave in Italy in 2020. Of the patients studied, 59.5% showed a decrease (≥2 fold) in neutralizing antibody titer against B.1.1.7, 83.3% against P.1, and 90.5% against B.1.351 with respect to the original strain. The reduction in antibody titers against all analyzed variants, and in particular P.1 and B.1.351, suggests that previous symptomatic infection might be not fully protective against exposure to SARS-CoV-2 variants carrying a set of relevant spike mutations. [ABSTRACT FROM AUTHOR]