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

The current pandemic produced by SARS-CoV-2 and its variants represent an example of the one health concept in which humans and animals are components of the same epidemiologic chain. Animal reservoirs of these viruses are thus the focus of surveillance programs, to monitor their circulation and evolution in potentially new hosts and reservoirs. In this work, we report the detection of the SARS-CoV-2 Gamma variant infection in four specimens of Chaetophractus villosus (big hairy armadillo/armadillo peludo) in Argentina. In addition to the finding of a new wildlife species susceptible to SARS-CoV-2 infection, the identification of the Gamma variant three months after its last detection in humans in Argentina is a noteworthy result, which can be due to alternative non-exclusive scenarios, such as unidentified viral reservoirs, unrecognized circulation in humans or species-specific variation in incubation periods.

Mortality Trend of Severe COVID-19 in Under-Vaccinated Population Admitted to ICU in French Amazonia.

(1) Background: Until December 2021, French Guiana (FG), located in South America, faced four consecutive COVID-19 epidemic waves. This study sought to analyze the mortality trend of severe COVID-19 patients admitted to the referral ICU of FG. (2) Methods: We conducted a prospective, observational, and non-interventional study in ICU at Cayenne Hospital. We included 383 patients older than 18 admitted with SARS-CoV-2-related pneumonia hospitalized from May 2020 to December 2021. The study covers three periods. Period 1 (Waves 1 and 2, original variant), period 2 (Wave 3, Gamma variant), and period 3 (Wave 4, Delta variant). (3) Results: The median age was 63 years (52-70). Frailty was diagnosed in 36 patients over 70 (32.4%). Only 4.8% of patients were vaccinated. The median ICU LOS was 10 days (6-19). Hospital mortality was 37.3%. It was 30.9% in period 1, 36.6% in period 2 (p = 0.329 vs. period 1), and 47.1% in period 3 (0.015 vs. period 1). In multivariate analysis, independent factors associated with hospital mortality included age greater than 40 years (]40-60 years] OR = 5.2, 95%CI: 1.4-19.5; (]60-70 years] OR = 8.5, 95%CI: 2.2-32; (]70+ years] OR = 17.9, 95%CI: 4.5-70.9), frailty (OR = 5.6, 95%CI: 2.2-17.2), immunosuppression (OR = 2.6, 95%CI: 1.05-6.7), and MV use (OR = 11, 95%CI: 6.1-19.9). This model had an overall sensitivity of 72%, a specificity of 80.4%, a positive predictive value of 68.7%, and a negative predictive value of 82.8%. (4) Conclusions: The mortality of severe COVID-19 patients in French Amazonia was higher during the Delta variant wave. This over-death could be explained by the virulence of the responsible SARS-CoV-2 variant and the under-vaccination coverage of the studied population.

Trends in the COVID-19 Pandemic in Italy during the Summers of 2020 (before Mass Vaccination), 2021 (after Primary Mass Vaccination) and 2022 (after Booster Mass Vaccination): A Real-World Nationwide Study Based on a Population of 58.85 Million People.

Like all RNA viruses, SARS-CoV-2 shows a high mutation rate, which has led to the emergence of new variants. Among them, Gamma and Delta developed at the turn of 2020-2021 in Amazonas and India, two ecoregions characterized by hot-humid weather, very similar to that of the summer season in Italy due to climate change, the first Western country to be hit hard by COVID-19 and to experience lockdown restrictions in a democratic framework of 58.85 million people. The aim of our research has been to evaluate the impact of climate on the COVID-19 pandemic in Italy during the summers of 2020 (before mass vaccination), 2021 (after primary mass vaccination) and 2022 (after booster mass vaccination), also taking into account the emergence of these two variants. METHODS: During the state of national health emergency and the Draghi government, the Civil Defense Department released the aggregate data coming from the Ministry of Health, the Higher Institute of Health, the Independent Provinces and the Italian Regions daily, in order to inform about the pandemic situation in Italy. Among these data there were the number of deaths, hospitalizations in intensive care units (ICU), non-ICU patients, contagions and performed swabs. By means of a team effort, we have collected and elaborated all these data, comparing the COVID-19 pandemic in Italy during the summers of 2020 (following the nationwide lockdown), 2021 and 2022. RESULTS: from the summer of 2020 to the summers of 2021 and 2022 all pandemic trend indicators have shown a sharp worsening in Italy. COVID-19 deaths increased by ≈298% and ≈834%, ICU hospitalizations by ≈386% and ≈310%, non-ICU hospitalizations by ≈224% and ≈600%, contagions by ≈627% and ≈6850% (i.e., ≈68.50 times), swabs by ≈354% and ≈370%, and the mean positivity rate passed from ≈1% to ≈2% and ≈20%, respectively. CONCLUSIONS: SARS-CoV-2 can be transmitted in any climate, including areas with hot and humid weather, and the emergence of variants adapted to hot-humid climates may result in summer COVID-19 outbreaks, even in neither tropical nor subtropical countries. Although COVID-19 vaccines can confer cross-protection against newly emerging variants, this cross-immunity is naturally not absolute but limited, considering that vaccine protection wanes significantly after 6 months. It follows that a subject vaccinated at the beginning of the winter will not be completely covered in the height of the summer, and we should not forget the unvaccinated. As a final remark, the long and strict nationwide lockdown made it possible to flatten SARS-CoV-2 circulation and, therefore, its negative impact on Italy during the summer of 2020.

Virulence Profiles of Wild-Type, P.1 and Delta SARS-CoV-2 Variants in K18-hACE2 Transgenic Mice.

Since December 2019, the world has been experiencing the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and we now face the emergence of several variants. We aimed to assess the differences between the wild-type (Wt) (Wuhan) strain and the P.1 (Gamma) and Delta variants using infected K18-hACE2 mice. The clinical manifestations, behavior, virus load, pulmonary capacity, and histopathological alterations were analyzed. The P.1-infected mice showed weight loss and more severe clinical manifestations of COVID-19 than the Wt and Delta-infected mice. The respiratory capacity was reduced in the P.1-infected mice compared to the other groups. Pulmonary histological findings demonstrated that a more aggressive disease was generated by the P.1 and Delta variants compared to the Wt strain of the virus. The quantification of the SARS-CoV-2 viral copies varied greatly among the infected mice although it was higher in P.1-infected mice on the day of death. Our data revealed that K18-hACE2 mice infected with the P.1 variant develop a more severe infectious disease than those infected with the other variants, despite the significant heterogeneity among the mice.

Cross-immunity against SARS-COV-2 variants of concern in naturally infected critically ill COVID-19 patients.

Critically ill patients infected with SARS-CoV-2 display adaptive immunity, but it is unknown if they develop cross-reactivity to variants of concern (VOCs). We profiled cross-immunity against SARS-CoV-2 VOCs in naturally infected, non-vaccinated, critically ill COVID-19 patients. Wave-1 patients (wild-type infection) were similar in demographics to Wave-3 patients (wild-type/alpha infection), but Wave-3 patients had higher illness severity. Wave-1 patients developed increasing neutralizing antibodies to all variants, as did patients during Wave-3. Wave-3 patients, when compared to Wave-1, developed more robust antibody responses, particularly for wild-type, alpha, beta and delta variants. Within Wave-3, neutralizing antibodies were significantly less to beta and gamma VOCs, as compared to wild-type, alpha and delta. Patients previously diagnosed with cancer or chronic obstructive pulmonary disease had significantly fewer neutralizing antibodies. Naturally infected ICU patients developed adaptive responses to all VOCs, with greater responses in those patients more likely to be infected with the alpha variant, versus wild-type.

Reduced neutralization against Delta, Gamma, Mu, and Omicron BA.1 variants of SARS-CoV-2 from previous non-Omicron infection.

The understanding of the host immune response to SARS-CoV-2 variants of concern is critical for improving diagnostics, therapy development, and vaccines. Here, we analyzed the level of neutralizing antibodies against SARS-CoV-2 D614G, Delta, Gamma, Mu, and Omicron variants in D614G infected healthcare workers during a follow-up up to 6 months after recovery. We followed up 76 patients: 60.5% were women and 39.5% men. The 96.1% and 3.9% were symptomatic and asymptomatic, respectively. The most frequent symptoms were headache, myalgia, and cough. The 65.8%, 65.8%, and 92.1% of the infected individuals were positive for neutralizing antibodies against D614G variant at 2, 4, and 6 months of follow-up, respectively. The 26.3%, 48.7% and 65.8% of patients neutralized Delta variant, 19.7%, 32.9% and 52.6% of patients neutralized Gamma, 7.9%, 19.7% and 44.7% of patients neutralized Mu, and 4.0%, 9.2% and 15.8% of patients neutralized Omicron. Low neutralization against Gamma and Mu variants was observed during the follow-up, and very low against the Omicron variant was detected during the same period. The median of neutralizing antibody titers against D614G and Delta variants increased significantly during the follow-up. An association was observed between the levels of neutralizing antibodies against D614G and Delta variants and the severity of the disease. Our results suggest an immune escape from neutralizing antibodies with the Omicron variant because of the many mutations localized in the S protein.

Virulence profiles of wild-type, P.1 and delta SARS-CoV-2 variants in K18-hACE2 transgenic mice

Since December 2019, the world has been experiencing the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and we now face the emergence of several variants. We aimed to assess the differences between the wild-type (Wt) (Wuhan) strain and the P.1 (Gamma) and Delta variants using infected K18-hACE2 mice. The clinical manifestations, behavior, virus load, pulmonary capacity, and histopathological alterations were analyzed. The P.1-infected mice showed weight loss and more severe clinical manifestations of COVID-19 than the Wt and Delta-infected mice. The respiratory capacity was reduced in the P.1-infected mice compared to the other groups. Pulmonary histological findings demonstrated that a more aggressive disease was generated by the P.1 and Delta variants compared to the Wt strain of the virus. The quantification of the SARS-CoV-2 viral copies varied greatly among the infected mice although it was higher in P.1-infected mice on the day of death. Our data revealed that K18-hACE2 mice infected with the P.1 variant develop a more severe infectious disease than those infected with the other variants, despite the significant heterogeneity among the mice.

Neutralization assays for SARS-CoV-2: Implications for assessment of protective efficacy of COVID-19 vaccines.

The WHO emergency use-listed (EUL) COVID-19 vaccines were developed against early strains of SARS-CoV-2. With the emergence of SARS-CoV-2 variants of concern (VOCs) - Alpha, Beta, Gamma, Delta and Omicron, it is necessary to assess the neutralizing activity of these vaccines against the VOCs. PubMed and preprint platforms were searched for literature on neutralizing activity of serum from WHO EUL vaccine recipients, against the VOCs, using appropriate search terms till November 30, 2021. Our search yielded 91 studies meeting the inclusion criteria. The analysis revealed a drop of 0-8.9-fold against Alpha variant, 0.3-42.4-fold against Beta variant, 0-13.8-fold against Gamma variant and 1.35-20-fold against Delta variant in neutralization titres of serum from the WHO EUL COVID-19 vaccine recipients, as compared to early SARS-CoV-2 isolates. The wide range of variability was due to differences in the choice of virus strains selected for neutralization assays (pseudovirus or live virus), timing of serum sample collection after the final dose of vaccine (day 0 to 8 months) and sample size (ranging from 5 to 470 vaccinees). The reasons for this variation have been discussed and the possible way forward to have uniformity across neutralization assays in different laboratories have been described, which will generate reliable data. Though in vitro neutralization studies are a valuable tool to estimate the performance of vaccines against the backdrop of emerging variants, the results must be interpreted with caution and corroborated with field-effectiveness studies.

Introduction and Establishment of SARS-CoV-2 Gamma Variant in New York City in Early 2021.

BACKGROUND: Monitoring the emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is an important public health objective. We investigated how the Gamma variant was established in New York City (NYC) in early 2021 in the presence of travel restrictions that aimed to prevent viral spread from Brazil, the country where the variant was first identified. METHODS: We performed phylogeographic analysis on 15 967 Gamma sequences sampled between 10 March and 1 May 2021, to identify geographic sources of Gamma lineages introduced into NYC. We identified locally circulating Gamma transmission clusters and inferred the timing of their establishment in NYC. RESULTS: We identified 16 phylogenetically distinct Gamma clusters established in NYC (cluster sizes ranged 2-108 genomes); most of them were introduced from Florida and Illinois and only 1 directly from Brazil. By the time the first Gamma case was reported by genomic surveillance in NYC on 10 March, the majority (57%) of circulating Gamma lineages had already been established in the city for at least 2 weeks. CONCLUSIONS: Although travel from Brazil to the United States was restricted from May 2020 through the end of the study period, this restriction did not prevent Gamma from becoming established in NYC as most introductions occurred from domestic locations.

The Biological Functions and Clinical Significance of SARS-CoV-2 Variants of Corcern.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuing to evolve, emerging novel variants with spike protein mutations. Although most mutations emerged in the SARS-CoV-2 genome are neutral or mildly deleterious, a small number of mutations can affect virus phenotype that confers the virus a fitness advantage. These mutations can enhance viral replication, raise the risk of reinfection and blunt the potency of neutralizing antibodies triggered by previous infection and vaccination. Since December 2020, the SARS-CoV-2 has emerged five quickly spreading strains, designated variants of concern (VOCs), including the Alpha (B.1.1.7) variant, the Beta (B.1.351) variant, the Gamma (P.1) variant, the Delta (B.1.617.2) variant and the Omicron (B.1.1.529) variant. These variants have a high number of the mutations in the spike protein that promotes viral cell entry through the angiotensin-converting enzyme -2 (ACE2). Mutations that have arisen in the receptor binding domain (RBD) of the spike protein are of great concern due to their potential to evade neutralizing antibodies triggered by previous infection and vaccines. The Alpha variant emerged in the United Kingdom in the second half of 2020 that has spread quickly globally and acquired the E484K mutation in the United Kingdom and the United States. The Beta and Gamma variants emerged in South Africa and Brazil, respectively, that have additional mutations at positions E484 and K417 in the RBD. SARS-CoV-2 variants containing the combination of N501Y, E484K, and K417N/T mutations exhibit remarkably decreased sensitivity to neutralizing antibodies mediated by vaccination or previous infection. The Gamma variant may result in more severe disease than other variants do even in convalescent individuals. The Delta variant emerged in India in December 2020 and has spread to many countries including the United States and the United Kingdom. The Delta variant has 8 mutations in the spike protein, some of which can influence immune responses to the key antigenic regions of RBD. In early November 2021, the Omicron (B.1.1.529) variant was first detected in Botswana and South Africa. The Omicron variant harbors more than 30 mutations in the spike protein, many of which are located within the RBD, which have been associated with increased transmissibility and immune evasion after previous infection and vaccination. Additionally, the Omicron variant contains 3 deletions and one insertion in the spike protein. Recently, the Omicron variant has been classified into three sublineages, including BA.1, BA.2, and BA.3, with strikingly different genetic characteristics. The Omicron BA.2 sublineage has different virological landscapes, such as transmissibility, pathogenicity and resistance to the vaccine-induced immunity compared to BA.1 and BA.3 sublineages. Mutations emerged in the RBD of the spike protein of VOCs increase viral replication, making the virus more infectious and more transmissible and enable the virus to evade vaccine-elicited neutralizing antibodies. Unfortunately, the emergence of novel SARS-CoV-2 VOCs has tempered early optimism regarding the efficacy of COVID-19 vaccines. This review addresses the biological and clinical significance of SARS-CoV-2 VOCs and their impact on neutralizing antibodies mediated by existing COVID-19 vaccines.

Absence of neutralizing antibodies against the Omicron SARS-CoV-2 variant in convalescent sera from individuals infected with the ancestral SARS-CoV-2 virus or its Gamma variant.

OBJECTIVES: The aim of the present study was to evaluate if neutralizing antibody responses induced by infection with the SARS-CoV-2 strain that was dominant at the beginning of the pandemic or by the Gamma variant was effective against the Omicron variant. METHODS: Convalescent sera from 109 individuals, never exposed to a SARS-CoV-2 vaccine, who had mild or moderate symptoms not requiring hospitalization following either a documented SARS-CoV-2 ancestral strain infection or a Gamma variant infection, were assayed for in vitro neutralizing antibody activity against their original strains and the Omicron variant. RESULTS: Following an infection with the ancestral strain, 56 (93.3%), 45 (77.6%) and 1 (1.7%) serum sample were positive for neutralizing antibodies against the ancestral, Gamma variant, and Omicron variant, respectively. After infection with the Gamma variant, 43 (87.8%) and 2 (4.1%) sera were positive for neutralizing antibodies against the Gamma and Omicron variants, respectively. CONCLUSIONS: Neutralizing antibodies generated following mild or moderate infection with the SARS-CoV-2 ancestral strain or the Gamma variant are not protective against the Omicron variant.

Molecular Dynamics and MM-PBSA Analysis of the SARS-CoV-2 Gamma Variant in Complex with the hACE-2 Receptor.

The SARS-CoV-2 virus, since its appearance in 2019, has caused millions of cases and deaths. To date, there is no effective treatment or a vaccine that is fully protective. Despite the efforts made by governments and health institutions around the globe to control its propagation, the evolution of the virus has accelerated, diverging into hundreds of variants. However, not all of them are variants of concern (VoC's). VoC's have appeared in different regions and throughout the two years of the pandemic they have spread around the world. Specifically, in South America, the gamma variant (previously known as P.1) appeared in early 2021, bringing with it a second wave of infections. This variant contains the N501Y, E484K and K417T mutations in the receptor binding domain (RBD) of the spike protein. Although these mutations have been described experimentally, there is still no clarity regarding their role in the stabilization of the complex with the human angiotensin converting enzyme 2 (hACE-2) receptor. In this article we dissect the influence of mutations on the interaction with the hACE-2 receptor using molecular dynamics and estimations of binding affinity through a screened version of the molecular mechanics Poisson Boltzmann surface area (MM-PBSA) and interaction entropy. Our results indicate that mutations E484K and K417T compensate each other in terms of binding affinity, while the mutation N501Y promotes a more convoluted effect. This effect consists in the adoption of a cis configuration in the backbone of residue Y495 within the RBD, which in turn promotes polar interactions with the hACE-2 receptor. These results not only correlate with experimental observations and complement previous knowledge, but also expose new features associated with the specific contribution of concerned mutations. Additionally, we propose a recipe to assess the residue-specific contribution to the interaction entropy.

Dynamics of COVID-19 in Amazonia: A history of government denialism and the risk of a third wave.

The city of Manaus (the capital of Brazil's state of Amazonas) has become a key location for understanding the dynamics of the global pandemic of COVID-19. Different groups of scientists have foreseen different scenarios, such as the second wave or that Manaus could escape such a wave by having reached herd immunity. Here we test five hypotheses that explain the second wave of COVID-19 in Manaus: 1) The greater transmissibility of the Amazonian (gamma or P.1) variant is responsible for the second wave; 2) SARS-CoV-2 infection levels during the first wave were overestimated by those foreseeing herd immunity, and the population remained below this threshold when the second wave began at the beginning of December 2020; 3) Antibodies acquired from infection by one lineage do not confer immunity against other lineages; 4) Loss of immunity has generated a feedback phenomenon among infected people, which could generate future waves, and 5) A combination of the foregoing hypotheses. We also evaluated the possibility of a third wave in Manaus despite advances in vaccination, the new wave being due to the introduction of the delta variant in the region and the loss of immunity from natural contact with the virus. We developed a multi-strain SEIRS (Susceptible-Exposed-Infected-Removed-Susceptible) model and fed it with data for Manaus on mobility, COVID-19 hospitalizations, numbers of cases and deaths. Our model contemplated the current vaccination rates for all vaccines applied in Manaus and the individual protection rates already known for each vaccine. Our results indicate that the SARS-CoV-2 gamma (P.1) strain that originated in the Amazon region is not the cause of the second wave of COVID-19 in Manaus, but rather this strain originated during the second wave and became predominant in January 2021. Our multi-strain SEIRS model indicates that neither the doubled transmission rate of the gamma variant nor the loss of immunity alone is sufficient to explain the sudden rise of hospitalizations in late December 2020. Our results also indicate that the most plausible explanation for the current second wave is a SARS-CoV-2 infection level at around 50% of the population in early December 2020, together with loss of population immunity and early relaxation of restrictive measures. The most-plausible model indicates that contact with one strain does not provide protection against other strains and that the gamma variant has a transmissibility rate twice that of the original SARS-CoV-2 strain. Our model also shows that, despite the advance of vaccination, and even if future vaccination advances at a steady pace, the introduction of the delta variant or other new variants could cause a new wave of COVID-19.

Case Report: SARS-CoV-2 Gamma Isolation From Placenta of a Miscarriage in Midwest, Brazil.

The present study investigated a SARS-CoV-2 infection in placenta and fetal samples from an early pregnancy miscarriage in Midwest Brazil. The Gamma variant was isolated and fully sequenced from the placenta sample, but not from fetal samples. Our findings highlight potential adverse perinatal outcomes caused by SARS-CoV-2 Gamma infection during pregnancy.

Epistasis at the SARS-CoV-2 Receptor-Binding Domain Interface and the Propitiously Boring Implications for Vaccine Escape.

At the time of this writing, December 2021, potential emergence of vaccine escape variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a grave global concern. The interface between the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein and the host receptor (ACE2) overlaps the binding site of principal neutralizing antibodies (NAb), limiting the repertoire of viable mutations. Nonetheless, variants with multiple RBD mutations have risen to dominance. Nonadditive, epistatic relationships among RBD mutations are apparent, and assessing the impact of such epistasis on the mutational landscape, particularly the risk of vaccine escape, is crucial. We employed protein structure modeling using Rosetta to compare the effects of all single mutants at the RBD-NAb and RBD-ACE2 interfaces for the wild type and Delta, Gamma, and Omicron variants. Overall, epistasis at the RBD interface appears to be limited, and the effects of most multiple mutations are additive. Epistasis at the Delta variant interface weakly stabilizes NAb interaction relative to ACE2 interaction, whereas in Gamma, epistasis more substantially destabilizes NAb interaction. Despite bearing many more RBD mutations, the epistatic landscape of Omicron closely resembles that of Gamma. Thus, although Omicron poses new risks not observed with Delta, structural constraints on the RBD appear to hamper continued evolution toward more complete vaccine escape. The modest ensemble of mutations relative to the wild type that are currently known to reduce vaccine efficacy is likely to contain the majority of all possible escape mutations for future variants, predicting the continued efficacy of the existing vaccines. IMPORTANCE Emergence of vaccine escape variants of SARS-CoV-2 is arguably the most pressing problem during the COVID-19 pandemic as vaccines are distributed worldwide. We employed a computational approach to assess the risk of antibody escape resulting from mutations in the receptor-binding domain of the spike protein of the wild-type SARS-CoV-2 virus as well as the Delta, Gamma, and Omicron variants. The efficacy of the existing vaccines against Omicron could be substantially reduced relative to the wild type, and the potential for vaccine escape is of grave concern. Our results suggest that although Omicron poses new evolutionary risks not observed for Delta, structural constraints on the RBD make continued evolution toward more complete vaccine escape from either Delta or Omicron unlikely. The modest set of escape-enhancing mutations already identified for the wild type likely include the majority of all possible mutations with this effect.

CoronaVac and ChAdOx1 Vaccination and Gamma Infection Elicited Neutralizing Antibodies against the SARS-CoV-2 Delta Variant.

The emergence of new SARS-CoV-2 variants represents a constant threat to world public health. The SARS-CoV-2 Delta variant was identified in late 2020 in India; since then, it has spread to many other countries, replacing other predominant lineages and raising concerns about vaccination efficiency. We evaluated the sensitivity of the Delta variant to antibodies elicited by COVID-19 vaccinated (CoronaVac and ChAdOx1) and convalescent individuals previously infected by earlier lineages and by the Gamma variant. No reduction in the neutralizing efficacy of the Delta variant was observed when compared to B lineage and a reduced neutralization was observed for the Gamma variant. Our results indicate that neutralization of the Delta variant is not compromised in individuals vaccinated by CoronaVac or ChAdOx1; however, a reduction in neutralization efficacy is expected for individuals infected by the Gamma variant, highlighting the importance of continuous vaccination even for previously infected individuals.

SARS-CoV-2 variants of concern display enhanced intrinsic pathogenic properties and expanded organ tropism in mouse models.

SARS-CoV-2 variants of concern (VOCs) display enhanced transmissibility and resistance to antibody neutralization. Comparing the early 2020 isolate EU-1 to the VOCs Alpha, Beta, and Gamma in mice transgenic for human ACE2 reveals that VOCs induce a broadened scope of symptoms, expand systemic infection to the gastrointestinal tract, elicit the depletion of natural killer cells, and trigger variant-specific cytokine production patterns. Gamma infections result in accelerated disease progression associated with increased immune activation and inflammation. All four SARS-CoV-2 variants induce pDC depletion in the lungs, paralleled by reduced interferon responses. Remarkably, VOCs also use the murine ACE2 receptor for infection to replicate in the lungs of wild-type animals, which induce cellular and innate immune responses that apparently curtail the spread of overt disease. VOCs thus display distinct intrinsic pathogenic properties with broadened tissue and host range. The enhanced pathogenicity of VOCs and their potential for reverse zoonotic transmission pose challenges to clinical and pandemic management.

Comparison of the First and Second Waves of the Coronavirus Disease 2019 Pandemic in Children and Adolescents in a Middle-Income Country: Clinical Impact Associated with Severe Acute Respiratory Syndrome Coronavirus 2 Gamma Lineage.

OBJECTIVE: To evaluate the severity and clinical outcomes of the SARS-CoV-2 gamma variant in children and adolescents hospitalized with COVID-19 in Brazil. STUDY DESIGN: In this observational retrospective cohort study, we performed an analysis of all 21 591 hospitalized patients aged <20 years with confirmed SARS-CoV-2 infection registered in a national database in Brazil. The cohort was divided into 2 groups according to the predominance of SARS-CoV-2 lineages (WAVE1, n = 11 574; WAVE2, n = 10 017). The characteristics of interest were age, sex, geographic region, ethnicity, clinical presentation, and comorbidities. The primary outcome was time to death, which was evaluated by competing-risks analysis, using cumulative incidence functions. A predictive Fine and Gray competing-risks model was developed based on the WAVE1 cohort with temporal validation in the WAVE2 cohort. RESULTS: Compared with children and adolescents admitted during the first wave, those admitted during the second wave had significantly more hypoxemia (52.5% vs 41.1%; P < .0001) and intensive care unit admissions (28.3% vs 24.9%; P < .0001) and needed more noninvasive ventilatory support (37.3% vs 31.6%; P < .0001). In-hospital deaths and death rates were 896 (7.7%) in the first wave and 765 (7.6%) in the second wave (P = .07). The prediction model of death included age, ethnicity, region, respiratory symptoms, and comorbidities. In the validation set (WAVE2), the C statistic was 0.750 (95% CI, 0.741-0.758; P < .0001). CONCLUSIONS: This large national study found a more severe spectrum of risk for pediatric patients with COVID-19 caused by the gamma variant. However, there was no difference regarding the probability of death between the waves.

Epidemiology of COVID-19 after Emergence of SARS-CoV-2 Gamma Variant, Brazilian Amazon, 2020-2021.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant has been hypothesized to cause more severe illness than previous variants, especially in children. Successive SARS-CoV-2 IgG serosurveys in the Brazilian Amazon showed that age-specific attack rates and proportions of symptomatic SARS-CoV-2 infections were similar before and after Gamma variant emergence.