Gamma Variants Research Articles

How well do different COVID-19 vaccines protect against different viral variants? A systematic review and meta-analysis.

While the efficacy of coronavirus disease 2019 (COVID-19) vaccines has been evaluated in numerous trials, comprehensive evidence on how protection by different vaccines has varied over time remains limited. We aimed to compare protective effects of different vaccines against different viral variants. To achieve this, we searched Medline, Cochrane Library and Embase for randomized controlled trials assessing the efficacy of COVID-19 vaccines. Forest plots using Mantel-Haenszel and random-effects models were generated showing risk ratios (RRs) and 95% CIs by vaccines and variants. We included 36 studies with 90 variant-specific primary outcomes. We found a RR of 0.26 (95% CI 0.21 to 0.31) against all variants overall, with the highest protective effects against the wild-type (RR 0.13; 95% CI 0.10 to 0.18), followed by Alpha (RR 0.26; 95% CI 0.18 to 0.36), Gamma (RR 0.34; 95% CI 0.21 to 0.55), Delta (RR 0.39; 95% CI 0.28 to 0.56) and Beta (RR 0.49; 95% CI 0.40 to 0.62) variants. Nucleic acid vaccines showed the highest protection levels against all variants (RR 0.11; 95% CI 0.08 to 0.15), followed by protein subunit, inactivated virus and viral vector. In conclusion, we found high but heterogenous levels of protection for most COVID-19 vaccines, with decreasing protective effects for vaccines based on traditional technologies as SARS-CoV-2 variants emerged over time. Novel nucleic acid-based vaccines offered substantially higher and more consistent protection.

Post-migration infection with SARS-CoV-2 in Venezuelan migrants: A laboratory-based epidemiological observational study

BackgroundSince 2015, over 6 million Venezuelans migrated to Colombia and neighboring countries. While most people adhered to lockdown measures, migrants kept moving during the COVID-19 pandemic. MethodTo investigate the extent of migration-associated SARS-CoV-2 infections, we interviewed 1209 adult Venezuelan migrants upon arrival to Bucaramanga, Colombia, 200 km from the Colombian-Venezuelan border along the main migration route during April–September 2021, collected individual-level socio-economic and clinical data, sampled blood and saliva, and assessed SARS-CoV-2 infection by serological, molecular and phylogenetic tools. ResultsSARS-CoV-2 RT-PCR positivity was 1.9 % (95 % Confidence Interval (CI), 1.2–2.9) without varying significantly over the study period (chi-square, p = 0.922) and significantly associated with stay in Colombia >14 days (p = 0.018; prevalence ratio 3.3, 95 % CI, 1.2–8.7). Pre-existing SARS-CoV-2-specific antibodies were neither significantly associated with preventing infection (Chi-square, p = 0.188), nor symptom development (Fisher, p = 0.246). Predominance and time of detection of SARS-CoV-2 Mu and Gamma variants in migrants in comparison to available genomic data suggested infection predominantly in Colombia. SARS-CoV-2 IgG-based seroprevalence was 34.2 % (95 % CI, 31.5–36.9). Detection of SARS-CoV-2-specific antibodies was significantly associated with previous contact with infected individuals (p = 0.002). ConclusionsSARS-CoV-2 infection occurred predominantly after immigration, potentially facilitated by densely populated border camps. Improved infrastructure and health care will prevent migration-associated spread of COVID-19 and other infectious diseases.

Design of the conserved epitope peptide of SARS-CoV-2 spike protein as the broad-spectrum COVID-19 vaccine

Our previous study has found that monoclonal antibodies targeting a conserved epitope peptide spanning from residues 1144 to 1156 of SARS-CoV-2 spike (S) protein, namely S(1144–1156), can broadly neutralize all of the prevalent SARS-CoV-2 strains, including the wild type, Alpha, Epsilon, Delta, and Gamma variants. In the study, S(1144–1156) was conjugated with bovine serum albumin (BSA) and formulated with Montanide ISA 51 adjuvant for inoculation in BALB/c mice to study its potential as a vaccine candidate. Results showed that the titers of S protein-specific IgGs and the neutralizing antibodies in mouse sera against various SARS-CoV-2 variants, including the Omicron sublineages, were largely induced along with three doses of immunization. The significant release of IFN-γ and IL-2 was also observed by ELISpot assays through stimulating vaccinated mouse splenocytes with the S(1144–1156) peptide. Furthermore, the vaccination of the S(1143–1157)- and S(1142–1158)-EGFP fusion proteins can elicit more SARS-CoV-2 neutralizing antibodies in mouse sera than the S(1144–1156)-EGFP fusion protein. Interestingly, the antisera collected from mice inoculated with the S(1144–1156) peptide vaccine exhibited better efficacy for neutralizing Omicron BA.2.86 and JN.1 subvariants than Omicron BA.1, BA.2, and XBB subvariants. Since the amino acid sequences of the S(1144–1156) are highly conserved among various SARS-CoV-2 variants, the immunogen containing the S(1144–1156) core epitope can be designed as a broadly effective COVID-19 vaccine.Key points• Inoculation of mice with the S(1144–1156) peptide vaccine can induce bnAbs against various SARS-CoV-2 variants.• The S(1144–1156) peptide stimulated significant release of IFN-γ and IL-2 in vaccinated mouse splenocytes.• The S(1143–1157) and S(1142–1158) peptide vaccines can elicit more SARS-CoV-2 nAbs in mice.

Comparison of immune response parameters between homologous and heterologous COVID-19 vaccines: A scoping review

It has been over 4 years since the emergence of the coronavirus disease 2019 (COVID-19) pandemic. This highly contagious respiratory infection has endangered the health of millions and significantly impacted healthcare systems and economies. Vaccines are believed to confer immunity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, reducing both the severity of infection and the spread of the virus. Within a short period, various COVID-19 vaccines were developed and extensively tested before being approved by the WHO for distribution and administration. Now, due to concerns about emerging new strains of the virus and limited vaccine availability, a heterologous vaccine strategy is being deployed. Therefore, this paper aims to conduct a scoping review of existing evidence to compare the immunogenicity of heterologous vaccines with homologous vaccines and determine which confers better immunity against COVID-19. A literature search was conducted across three electronic databases (Ovid MEDLINE, PubMed, and Scopus). The retrieved studies were screened for relevance and eligibility using the online platform Covidence. A total of 31 articles were shortlisted for data extraction and analysis. Among these, 21 were observational studies, and 10 were clinical trials. The analysis demonstrated that participants who received heterologous vaccination regimens generated higher levels of IgG antibodies against the spike protein of SARS-CoV-2, antibodies targeting the receptor-binding domain, and T-cell responses compared to those who received homologous vaccination regimens. Furthermore, heterologous vaccination produced higher titers of neutralizing antibodies against several variants of concern (VOC), including Alpha, Beta, Gamma, Delta, and Omicron. No severe vaccine-related adverse events were reported in these studies, and common local and systemic side effects were manageable. Overall, heterologous vaccination regimes induced strong humoral and cellular immunity, comparable to homologous vaccination regimes, with stronger neutralizing antibody activity against VOCs.

Comparison of the Neutralization Power of Sotrovimab Against SARS-CoV-2 Variants: Development of a Rapid Computational Method.

The rapid evolution of SARS-CoV-2 imposed a huge challenge on disease control. Immune evasion caused by genetic variations of the SARS-CoV-2 spike protein's immunogenic epitopes affects the efficiency of monoclonal antibody-based therapy of COVID-19. Therefore, a rapid method is needed to evaluate the efficacy of the available monoclonal antibodies against the new emerging variants or potential novel variants. The aim of this study is to develop a rapid computational method to evaluate the neutralization power of anti-SARS-CoV-2 monoclonal antibodies against new SARS-CoV-2 variants and other potential new mutations. The amino acid sequence of the extracellular domain of the spike proteins of the severe acute respiratory syndrome coronavirus (GenBank accession number YP_009825051.1) and SARS-CoV-2 (GenBank accession number YP_009724390.1) were used to create computational 3D models for the native spike proteins. Specific mutations were introduced to the curated sequence to generate the different variant spike models. The neutralization potential of sotrovimab (S309) against these variants was evaluated based on its molecular interactions and Gibbs free energy in comparison to a reference model after molecular replacement of the reference receptor-binding domain with the variant's receptor-binding domain. Our results show a loss in the binding affinity of the neutralizing antibody S309 with both SARS-CoV and SARS-CoV-2. The binding affinity of S309 was greater to the Alpha, Beta, Gamma, and Kappa variants than to the original Wuhan strain of SARS-CoV-2. However, S309 showed a substantially decreased binding affinity to the Delta and Omicron variants. Based on the mutational profile of Omicron subvariants, our data describe the effect of the G339H and G339D mutations and their role in escaping antibody neutralization, which is in line with published clinical reports. This method is rapid, applicable, and of interest to adapt the use of therapeutic antibodies to the treatment of emerging variants. It could be applied to antibody-based treatment of other viral infections.

6684 Multi-Dose BCG Vaccination for Protection Against COVID-19 Disease and Other Respiratory Infections in Subjects with Type 1 Diabetes Late in the US Pandemic

Abstract Disclosure: W. Kühtreiber: None. E. Hostetter: None. G.E. Wolfe: None. M. Vaishnaw: None. R. Goldstein: None. E. Bulczynski: None. N. Hullavarad: None. J.E. Braley: None. H. Zheng: None. D.L. Faustman: None. A Phase II clinical trial previously reported that multiple doses of the bacillus Calmette-Guerin (BCG) vaccine, originally developed for tuberculosis prevention, could protect at-risk individuals with type 1 diabetes (T1D) against COVID-19 disease and infectious diseases early in the pandemic in the United States (US) (Cell Rep Med 2022). As SARS-CoV-2 evolved, COVID-19 disease became more transmissible, but less lethal. In a new, Phase III, randomized, double-blinded, placebo-controlled trial, we tested whether at-risk individuals with T1D given multi-dose, intradermal BCG would be protected against COVID-19 and other infectious diseases (2:1 randomization; BCG: n=93; placebo: n=48). The trial was conducted late in the COVID-19 pandemic during sequential dominance of Beta, Gamma, Delta and Omicron variants. All participants were US citizens and were negative for prior BCG vaccination and negative for tuberculosis. Two co-primary endpoints were protection from COVID-19 disease and platform protection from all infectious diseases. From April 2021 to November 2022, Tokyo-strain BCG vaccination provided significant protection against COVID-19 disease (p=0.023) and strong platform protection against all infectious diseases (p<0.0001). Over the 19-month course of the study, commercial COVID-19 vaccines were rolled out. An observational analysis of the placebo control group (i.e., no BCG vaccination) showed that COVID-19 mRNA vaccination alone provided no protection from COVID-19 disease in the enrolled population (p=0.43). BCG vaccination efficacy against COVID-19 and infectious disease in T1D was unaffected by concurrent COVID-19 vaccinations (observational analysis). These data suggest that BCG has efficacy against a range of SARS-CoV-2 variants, in contrast to current COVID-19 vaccines, which have narrow efficacy against specific viral variants. Further, it shows that individuals with T1D represent a vulnerable population for whom BCG appears to be the only effective vaccine against COVID-19 disease and confirms that, in the US, BCG vaccination protects against infectious disease as well. Presentation: 6/3/2024

Unmasking the Global Journey: Investigation of SARS-CoV-2 Variants of Interest Across Various Regions Through Whole-Genome and Phylogenetic Analysis

Background: The prolonged course of the Coronavirus Disease 2019 (COVID-19) pandemic and the virus's high mutation rate have sparked widespread interest in studying Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Research has shown that SARS-CoV-2 has evolved into numerous variants since its discovery. Objectives: This study aimed to investigate the differences in SARS-CoV-2 Variants of Interest (VOI) and Variants of Concern (VOC) from different geographical regions through phylogenetic analysis and mutational analysis. Methods: A total of 700 SARS-CoV-2 whole-genome sequences were retrieved from the GISAID database from January 1, 2021, to December 31, 2021. These sequences were aligned with the reference sequence (NC_045512) using Clustal Omega version 1.2.4. A phylogenetic tree was constructed using the IQ-TREE web server and visualized using ItoL. Results: The results revealed a fully resolved maximum likelihood tree with statistical support based on bootstrap values. The analysis demonstrated that Delta variant sequences clustered separately from other VOIs, VOCs, and outgroups. The shorter topology of the Delta variant showed that Africa branched away, similar to the Lambda and Gamma variants. Additionally, structural analysis identified three primarily uniform clusters in Europe, North America, and South America, which corresponded to the sister relationships observed in Clades 1, 2, and 7 topologies. These evolutionary trees were later linked to mutations in the spike, nucleocapsid, and nsp3 proteins, which displayed a high number of mutations. Conclusions: This study provides new insights into the evolving mutations of SARS-CoV-2 VOIs and VOCs across different regions of the world, contributing to our understanding of viral pathogenicity.

Sputnik V-Induced Antibodies against SARS-CoV-2 Variants during the Dissemination of the Gamma Variant in Venezuela.

The COVID-19 pandemic was characterized by the emergence and succession of SARS-CoV-2 variants able to evade the antibody response induced by natural infection and vaccination. To evaluate the IgG reactivity and neutralizing capacity of the serum of individuals vaccinated with Sputnik V (105 volunteers vaccinated) against different viral variants. IgG reactivity to the Spike protein (S) was evaluated by ELISA. A plaque reduction neutralization test was performed using different viral variant isolates. At 42 days post-vaccination, the frequency of recognition and reactivity to the S protein of the Omicron variant was lower compared to that of the other variants. In general, a higher average neutralization titer was seen against the ancestral variant compared to the variants, especially Omicron. However, some sera exhibited a higher neutralization titer to the Gamma variant compared to the ancestral variant, suggesting unapparent exposure during the clinical trial. Antibodies induced by Sputnik V can recognize, persist, and neutralize SARS-CoV-2 variants, with Omicron being the one that best evades this response. These results represent a unique report on the humoral response induced by a globally lesser-studied vaccine in terms of efficacy and immune escape, offering insights into developing vaccines targeting unknown coronaviruses.

The comparison of pathogenicity among SARS-CoV-2 variants in domestic cats

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected or isolated from domestic cats. It is unclear whether cats play an important role in the SARS-CoV-2 transmission cycle. In this study, we examined the susceptibility of cats to SARS-CoV-2, including wild type and variants, by animal experiments. Cats inoculated with wild type, gamma, and delta variants secreted a large amount of SARS-CoV-2 for 1 week after the inoculation from nasal, oropharyngeal, and rectal routes. Only 100 TCID50 of virus could infect cats and replicate well without severe clinical symptoms. In addition, one cat inoculated with wild type showed persistent virus secretion in feces for over 28 days post-inoculation (dpi). The titer of virus-neutralizing (VN) antibodies against SARS-CoV-2 increased from 11 dpi, reaching a peak at 14 dpi. However, the omicron variant could not replicate well in cat tissues and induced a lower titer of VN antibodies. It is concluded that cats were highly susceptible to SARS-CoV-2 infection, but not to the Omicron Variant, which caused the attenuated pathogenicity.

Maternal Immunization with Adjuvanted Recombinant Receptor-Binding Domain Protein Provides Immune Protection against SARS-CoV-2 in Infant Monkeys.

Maternal vaccinations administered prior to conception or during pregnancy enhance the immune protection of newborn infants against many pathogens. A feasibility experiment was conducted to determine if monkeys can be used to model the placental transfer of maternal antibody against SARS-CoV-2. Six adult rhesus monkeys were immunized with adjuvanted recombinant-protein antigens comprised of receptor-binding domain human IgG1-Fc fusion proteins (RBD-Fc) containing protein sequences from the ancestral-Wuhan or Gamma variants. The female monkeys mounted robust and sustained anti-SARS-CoV-2 antibody responses. Blood samples collected from their infants after delivery verified prenatal transfer of high levels of spike-specific IgG, which were positively correlated with maternal IgG titers at term. In addition, an in vitro test of ACE2 neutralization indicated that the infants' IgG demonstrated antigen specificity, reflecting prior maternal immunization with either Wuhan or Gamma-variant antigens. All sera showed stronger ACE2-RBD binding inhibition when variants in the assay more closely resembled the vaccine RBD sequence than with more distantly related variants (i.e., Delta and Omicron). Monkeys are a valuable animal model for evaluating new vaccines that can promote maternal and infant health. Further, the findings highlight the enduring nature and safety of the immune protection elicited by an adjuvanted recombinant RBD-Fc vaccine.

Analyzing the worldwide progression of COVID-19 cases and deaths using nonlinear mixed-effects model.

COVID-19 is an infectious disease that continues to spread worldwide. A precise estimation of the cases and deaths due to COVID-19 would allow for appropriate consideration of healthcare resource allocation, public health response, and vaccination and economic planning, to minimize social damage. In this study, we analyzed the progression of COVID-19 cases and deaths until January 2022 in 156 countries using a nonlinear mixed-effect model based on the SIR framework. Given the major changes in mortality from infection, risk of re-infection and social responses, the analysis was limited to the period before the emergence of the Omicron variant. The impact of infection prevention measures in various countries was assessed, with a specific focus on estimating the effectiveness of lockdowns, where the effect was assumed to change over time. By accounting for excess mortality, our analysis allowed the estimation of unreported cases and deaths, and thus providing a more comprehensive understanding of the impact of pandemic. In the analysis, we identified gross domestic product (GDP), proportion of people aged 65 years or older, latitude of the capital city on transmissibility of infection, and city population and cardiovascular death rate on mortality rate as significant influencing factors. Furthermore, the differences in transmissibility and mortality rates by variants and the effect of vaccination on the mortality rate were assessed. The transmissibility has increased by odds ratios of 1.2 to 1.4 in Beta, Gamma, and Delta variants; mortality rate has increased by odds ratios of 1.7, 2.2, and 1.4 in Beta, Gamma, and Delta variants, respectively; and vaccination decreased the mortality rate by odds ratios of 0.4 and 0.1 in Delta and other variants, respectively.

Dynamic clade transitions and the influence of vaccination on the spatiotemporal circulation of SARS-CoV-2 variants

Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

Human mobility patterns in Brazil to inform sampling sites for early pathogen detection and routes of spread: a network modelling and validation study

Detecting and foreseeing pathogen dispersion is crucial in preventing widespread disease transmission. Human mobility is a fundamental issue in human transmission of infectious agents. Through a mobility data-driven approach, we aimed to identify municipalities in Brazil that could comprise an advanced sentinel network, allowing for early detection of circulating pathogens and their associated transmission routes. In this modelling and validation study, we compiled a comprehensive dataset on intercity mobility spanning air, road, and waterway transport from the Brazilian Institute of Geography and Statistics (2016 data), National Transport Confederation (2022), and National Civil Aviation Agency (2017-23). We constructed a graph-based representation of Brazil's mobility network. The Ford-Fulkerson algorithm was used to rank the 5570 Brazilian cities according to their suitability as sentinel locations, allowing us to predict the most suitable locations for early detection and to track the most likely trajectory of a newly emerged pathogen. We also obtained SARS-CoV-2 genetic data from Brazilian municipalities during the early stage (Feb 25-April 30, 2020) of the virus's introduction and the gamma (P.1) variant emergence in Manaus (Jan 6-March 1, 2021), for the purposes of model validation. We found that flights alone transported 79·9 million (95% CI 58·3-101·4 million) passengers annually within Brazil during 2017-22, with seasonal peaks occurring in late spring and summer, and road and river networks had a maximum capacity of 78·3 million passengers weekly in 2016. By analysing the 7 746 479 most probable paths originating from source nodes, we found that 3857 cities fully cover the mobility pattern of all 5570 cities in Brazil, 557 (10·0%) of which cover 6 313 380 (81·5%) of the mobility patterns in our study. By strategically incorporating mobility patterns into Brazil's existing influenza-like illness surveillance network (ie, by switching the location of 111 of 199 sentinel sites to different municipalities), our model predicted that mobility coverage would have a 33·6% improvement from 4 059 155 (52·4%) mobility patterns to 5 422 535 (70·0%) without expanding the number of sentinel sites. Our findings are validated with genomic data collected during the SARS-CoV-2 pandemic period. Our model accurately mapped 22 (51%) of 43 clade 1-affected cities and 28 (60%) of 47 clade 2-affected cities spread from São Paulo city, and 20 (49%) of 41 clade 1-affected cities and 28 (58%) of 48 clade 2-affected cities spread from Rio de Janeiro city, Feb 25-April 30, 2020. Additionally, 224 (73%) of the 307 suggested early-detection locations for pathogens emerging in Manaus corresponded with the first cities affected by the transmission of the gamma variant, Jan 6-16, 2021. By providing essential clues for effective pathogen surveillance, our results have the potential to inform public health policy and improve future pandemic response efforts. Our results unlock the potential of designing country-wide clinical sample collection networks with mobility data-informed approaches, an innovative practice that can improve current surveillance systems. Rockefeller Foundation.

Safety and durability of mRNA-1273–induced SARS-CoV-2 immune responses in adolescents: results from the phase 2/3 TeenCOVE trial

Longitudinal changes in vaccination-induced immune response remain inadequately characterized in adolescents. We present long-term safety, immunogenicity, and COVID-19 incidence following a 2-dose mRNA-1273100-μg primary series, and immunogenicity following a single dose of mRNA-1273 50 μg in vaccine-naïve adolescents. TeenCOVE (NCT04649151) Part 1 randomized adolescents (12-17 years) to 2-dose mRNA-1273100 μg (n=2490) or placebo (n=1243) 28 days apart. Subsequently, placebo recipients (n=91) could receive open-label mRNA-1273. Primary objectives included prespecified adverse events through 12 months; secondary objectives were COVID-19 incidence and neutralizing and spike-binding antibodies (nAbs/bAbs) against SARS-CoV-2 (ancestral/variants) through 12 months (study period: December 2020-January 2022). In Part 2, vaccine-naïve adolescents (n=52) received up to 2 doses of mRNA-1273 50 μg; interim analysis included Day 28 (D28) nAbs post-injection 1 in SARS-CoV-2-baseline-positive participants (serologic/virologic evidence of prior infection). In SARS-CoV-2-baseline-negative adolescents (N=369), mRNA-1273 induced robust nAb responses versus baseline (geometric mean concentration [GMC]=11; 95% CI, 11-12) at D28 (1868 [1759-1985]), 6 months (625 [583-670]) and 12 months (550 [490-618]) post-injection 2. Similar bAb responses were observed to alpha/beta/delta/gamma variants; nAb/bAb responses were similar in SARS-CoV-2-baseline-positive adolescents. The 2-dose mRNA-1273100-μg primary series was generally well-tolerated; one case of nonserious, moderate, probable acute myocarditis resolved by 8 days from symptom onset. A single dose of mRNA-1273 50 μg in SARS-CoV-2-baseline-positive adolescents induced higher D28 nAb GMCs against ancestral SARS-CoV-2 than 2-dose mRNA-1273100μg in young adults (geometric mean ratio=4.322 [3.274-5.707]). The overall risk-benefit profile of mRNA-1273 remains favorable in adolescents, with durable 12-month immune responses against SARS-CoV-2 (ancestral/variants). A single mRNA-1273 50-μg injection in vaccine-naïve adolescents elicited robust immune responses against SARS-CoV-2. This project has been funded in whole or in part with federal funds by the Department of Health and Human Services, United States; Administration for Strategic Preparedness and Response, United States; Biomedical Advanced Research and Development Authority, United States, under Contract No. 75A50120C00034. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Department of Health and Human Services or its components.

Equal Maintenance of Anti-SARS-CoV-2 Antibody Levels Induced by Heterologous and Homologous Regimens of the BNT162b2, ChAdOx1, CoronaVac and Ad26.COV2.S Vaccines: A Longitudinal Study Up to the 4th Dose of Booster.

Several technological approaches have been used to develop vaccines against COVID-19, including those based on inactivated viruses, viral vectors, and mRNA. This study aimed to monitor the maintenance of anti-SARS-CoV-2 antibodies in individuals from Brazil according to the primary vaccination regimen, as follows: BNT162b2 (group 1; 22) and ChAdOx1 (group 2; 18). Everyone received BNT162b2 in the first booster while in the second booster CoronaVac, Ad26.COV2.S, or BNT162b2. Blood samples were collected from 2021 to 2023 to analyze specific RBD (ELISA) and neutralizing antibodies (PRNT50). We observed a progressive increase in anti-RBD and neutralizing antibodies in each subsequent dose, remaining at high titers until the end of follow-up. Group 1 had higher anti-RBD antibody titers than group 2 after beginning the primary regimen, with significant differences after the 2nd and 3rd doses. Group 2 showed a more expressive increase after the first booster with BNT162B2 (heterologous booster). Group 2 also presented high levels of neutralizing antibodies against the Gamma and Delta variants until five months after the second booster. In conclusion, the circulating levels of anti-RBD and neutralizing antibodies against the two variants of SARS-CoV-2 were durable even five months after the 4th dose, suggesting that periodic booster vaccinations (homologous or heterologous) induced long-lasting immunity.

Early mutational signatures and transmissibility of SARS-CoV-2 Gamma and Lambda variants in Chile

Genomic surveillance (GS) programmes were crucial in identifying and quantifying the mutating patterns of SARS-CoV-2 during the COVID-19 pandemic. In this work, we develop a Bayesian framework to quantify the relative transmissibility of different variants tailored for regions with limited GS. We use it to study the relative transmissibility of SARS-CoV-2 variants in Chile. Among the 3443 SARS-CoV-2 genomes collected between January and June 2021, where sampling was designed to be representative, the Gamma (P.1), Lambda (C.37), Alpha (B.1.1.7), B.1.1.348, and B.1.1 lineages were predominant. We found that Lambda and Gamma variants’ reproduction numbers were 5% (95% CI: [1%, 14%]) and 16% (95% CI: [11%, 21%]) larger than Alpha’s, respectively. Besides, we observed a systematic mutation enrichment in the Spike gene for all circulating variants, which strongly correlated with variants’ transmissibility during the studied period (r = 0.93, p-value = 0.025). We also characterised the mutational signatures of local samples and their evolution over time and with the progress of vaccination, comparing them with those of samples collected in other regions worldwide. Altogether, our work provides a reliable method for quantifying variant transmissibility under subsampling and emphasises the importance of continuous genomic surveillance.

Differential epitope prediction across diverse circulating variants of SARS-COV-2 in Brazil

COVID-19, caused by the SARS-COV-2 virus, induces numerous immunological reactions linked to the severity of the clinical condition of those infected. The surface Spike protein (S protein) present in Sars-CoV-2 is responsible for the infection of host cells. This protein presents a high rate of mutations, which can increase virus transmissibility, infectivity, and immune evasion. Therefore, we propose to evaluate, using immunoinformatic techniques, the predicted epitopes for the S protein of seven variants of Sars-CoV-2. MHC class I and II epitopes were predicted and further assessed for their immunogenicity, interferon-gamma (IFN-γ) inducing capacity, and antigenicity. For B cells, linear and structural epitopes were predicted. For class I MHC epitopes, 40 epitopes were found for the clades of Wuhan, Clade 2, Clade 3, and 20AEU.1, Gamma, and Delta, in addition to 38 epitopes for Alpha and 44 for Omicron. For MHC II, there were differentially predicted epitopes for all variants and eight equally predicted epitopes. These were evaluated for differences in the MHC II alleles to which they would bind. Regarding B cell epitopes, 16 were found in the Wuhan variant, 14 in 22AEU.1 and in Clade 3, 15 in Clade 2, 11 in Alpha and Delta, 13 in Gamma, and 9 in Omicron. When compared, there was a reduction in the number of predicted epitopes concerning the Spike protein, mainly in the Delta and Omicron variants. These findings corroborate the need for updates seen today in bivalent mRNA vaccines against COVID-19 to promote a targeted immune response to the main circulating variant, Omicron, leading to more robust protection against this virus and avoiding cases of reinfection. When analyzing the specific epitopes for the RBD region of the spike protein, the Omicron variant did not present a B lymphocyte epitope from position 390, whereas the epitope at position 493 for MHC was predicted only for the Alpha, Gamma, and Omicron variants.

An Outbreak of SARS-CoV-2 in Captive Armadillos Associated with Gamma Variant in Argentina

An Outbreak of SARS-CoV-2 in Captive Armadillos Associated with Gamma Variant in Argentina

Associations between epidemiological and laboratory parameters and disease severity in hospitalized patients with COVID-19 during first and second epidemic waves in middle south Mato Grosso.

COVID-19 is a multisystemic disease characterized by respiratory distress. Disease severity is associated with several factors. Here we characterize virological findings and evaluate the association of laboratorial, epidemiological, virological findings and clinical outcomes of 251 patients during the first and second epidemic waves of COVID-19. This transversal study used biological samples and data from patients hospitalized with COVID-19 between May 2020 and August 2021 in the metropolitan region of Cuiabá, Mato Grosso Brazil. Biological samples were subjected to RT-qPCR and MinION sequencing. Univariate and multivariate logistic regression and Odds ratio were used to correlate clinical, laboratorial, epidemiological data. Patients were represented by males (61.7%) with mean age of 52.4 years, mild to moderate disease (49,0%), overweight/obese (69.3%), with comorbidities (66.1%) and evolving to death (55.38%). Severe cases showing symptoms for prolonged time, ≥ 25% of ground-glass opacities in the lungs and fatality rate increased significantly in second wave. Fatality was statistically associated to > 61 years of age,>25% ground-glass opacities in the lungs, immune, cardiac, or metabolic comorbidities. Higher viral load (p < 0.01/p = 0.02 in each wave), decreased erythrocyte (p < 0.01), hemoglobin (p < 0.05/p < 0.01), hematocrit (p < 0.01), RDW (p < 0.01), lymphocyte (p < 0.01), increased leucocyte (p < 0.01), neutrophil (p < 0.01) and CRP levels (p < 0.01) showed significant association with fatality in both waves, as did Neutrophil/Platelet (NPR; p < 0.01), Neutrophil/Lymphocyte (NLR; p < 0.01) and Monocyte/Lymphocyte ratio (MLR; p < 0.01). SARS-CoV-2 genomes from lineage B.1.1.33(n = 8) and Gamma/P.1(n = 15) shared 6/7 and 20/23 lineage-defining mutations, respectively. Severity and mortality of COVID-19 associated with a panel of epidemiological and laboratorial findings, being second wave, caused by Gamma variant, more severe in this in-hospital population.

Pseudotyped virus infection of multiplexed ACE2 libraries reveals SARS-CoV-2 variant shifts in receptor usage.

Pairwise compatibility between virus and host proteins can dictate the outcome of infection. During transmission, both inter- and intraspecies variabilities in receptor protein sequences can impact cell susceptibility. Many viruses possess mutable viral entry proteins and the patterns of host compatibility can shift as the viral protein sequence changes. This combinatorial sequence space between virus and host is poorly understood, as traditional experimental approaches lack the throughput to simultaneously test all possible combinations of protein sequences. Here, we created a pseudotyped virus infection assay where a multiplexed target-cell library of host receptor variants can be assayed simultaneously using a DNA barcode sequencing readout. We applied this assay to test a panel of 30 ACE2 orthologs or human sequence mutants for infectability by the original SARS-CoV-2 spike protein or the Alpha, Beta, Gamma, Delta, and Omicron BA1 variant spikes. We compared these results to an analysis of the structural shifts that occurred for each variant spike's interface with human ACE2. Mutated residues were directly involved in the largest shifts, although there were also widespread indirect effects altering interface structure. The N501Y substitution in spike conferred a large structural shift for interaction with ACE2, which was partially recreated by indirect distal substitutions in Delta, which does not harbor N501Y. The structural shifts from N501Y greatly influenced the set of animal orthologs the variant spike was capable of interacting with. Out of the thirteen non-human orthologs, ten exhibited unique patterns of variant-specific compatibility, demonstrating that spike sequence changes during human transmission can toggle ACE2 compatibility and potential susceptibility of other animal species, and cumulatively increase overall compatibilities as new variants emerge. These experiments provide a blueprint for similar large-scale assessments of protein compatibility during entry by diverse viruses. This dataset demonstrates the complex compatibility relationships that occur between variable interacting host and virus proteins.