Comparative epidemic expansion of SARS-CoV-2 variants Delta and Omicron in the Brazilian State of Amazonas.

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.

Comparative epidemic expansion of SARS-CoV-2 variants Delta and Omicron in Amazonas, a Brazilian setting with high levels of hybrid immunity

The SARS-CoV-2 variants of concern (VOCs) Delta and Omicron spread globally during mid and late 2021, respectively, with variable impact according to the immune population landscape. In this study, we compare the dissemination dynamics of these VOCs in the Amazonas state, one of Brazils most heavily affected regions. We sequenced the virus genome from 4,128 patients collected in Amazonas between July 1st, 2021 and January 31st, 2022 and investigated the lineage replacement dynamics using a phylodynamic approach. The VOCs Delta and Omicron displayed similar patterns of phylogeographic spread but significantly different epidemic dynamics. The Delta and Omicron epidemics were fueled by multiple introduction events, followed by the successful establishment of a few local transmission lineages of considerable size that mainly arose in the Capital, Manaus. The VOC Omicron spread and became dominant much faster than the VOC Delta. We estimate that under the same epidemiological conditions, the average Re of Omicron was [~]3.3 times higher than that of Delta and the average Re of the Delta was [~]1.3 times higher than that of Gamma. Furthermore, the gradual replacement of Gamma by Delta occurred without an upsurge of COVID-19 cases, while the rise of Omicron fueled a sharp increase in SARS-CoV-2 infection. The Omicron wave displayed a shorter duration and a clear decoupling between the number of SARS-CoV-2 cases and deaths compared with previous (B.1.* and Gamma) waves in the Amazonas state. These findings suggest that the high level of hybrid immunity (infection plus vaccination) acquired by the Amazonian population by mid-2021 was able to limit the spread of the VOC Delta and was also probably crucial to curb the number of severe cases, although not the number of VOC Omicron new infections.

Malaria absorption peaks acquired through the skin of patients with infrared light can detect patients with varying parasitemia.

To eliminate malaria, scalable tools that are rapid, affordable, and can detect patients with low parasitemia are required. Non-invasive diagnostic tools that are rapid, reagent-free, and affordable would also provide a justifiable platform for testing malaria in asymptomatic patients. However, non-invasive surveillance techniques for malaria remain a diagnostic gap. Here, we show near-infrared Plasmodium absorption peaks acquired non-invasively through the skin using a miniaturized hand-held near-infrared spectrometer. Using spectra from the ear, these absorption peaks and machine learning techniques enabled non-invasive detection of malaria-infected human subjects with varying parasitemia levels in less than 10 s.

Receptor binding and escape from Beta antibody responses drive Omicron-B.1.1.529 evolution

On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.

A case series of SARS-CoV-2 reinfections caused by the variant of concern Gamma in Brazil

The rapid spread of the SARS-CoV-2 Variant of Concern (VOC) Gamma during late 2020 and early 2021 in Brazilian settings with high seroprevalence raised some concern about the potential role of reinfections in driving the epidemic. Very few cases of reinfection associated with the VOC Gamma, however, have been reported. Here we describe 25 cases of SARS-CoV-2 reinfection confirmed by real-time RT-PCR twice within months apart in Brazil. SARS-CoV-2 genomic analysis confirmed that individuals were primo-infected between March and December 2020 with distinct viral lineages, including B.1.1, B.1.1.28, B.1.1.33, B.1.195 and P.2, and then reinfected with the VOC Gamma between 3 to 12 months after primo-infection. The overall mean cycle threshold (Ct) value of the first (25.7) and second (24.5) episodes were roughly similar for the whole group and 14 individuals displayed mean Ct values < 25.0 at reinfection. Sera of 14 patients tested by plaque reduction neutralization test after reinfection displayed detectable neutralizing antibodies against Gamma and other SARS-CoV-2 variants (B.1.33, B.1.1.28 and Delta). All individuals have milder or no symptoms after reinfection and none required hospitalization. The present study demonstrates that the VOC Gamma was associated with reinfections during the second Brazilian epidemic wave in 2021 and raised concern about the potential infectiousness of reinfected subjects. Although individuals here analyzed failed to mount a long-term sterilizing immunity, they developed a high anti-Gamma neutralizing antibody response after reinfection that may provide some protection against severe disease.

High anti-SARS-CoV-2 antibody seroconversion rates before the second wave in Manaus, Brazil, and the protective effect of social behaviour measures: results from the prospective DETECTCoV-19 cohort.

BACKGROUND: The city of Manaus, Brazil, has seen two collapses of the health system due to the COVID-19 pandemic. We report anti-SARS-CoV-2 nucleocapsid IgG antibody seroconversion rates and associated risk factors in Manaus residents before the second wave of the epidemic in Brazil. METHODS: A convenience sample of adult (aged ≥18 years) residents of Manaus was recruited through online and university website advertising into the DETECTCoV-19 study cohort. The current analysis of seroconversion included a subgroup of DETECTCoV-19 participants who had at least two serum sample collections separated by at least 4 weeks between Aug 19 and Oct 2, 2020 (visit 1), and Oct 19 and Nov 27, 2020 (visit 2). Those who reported (or had no data on) having a COVID-19 diagnosis before visit 1, and who were positive for anti-SARS-CoV-2 nucleocapsid IgG antibodies at visit 1 were excluded. Using an in-house ELISA, the reactivity index (RI; calculated as the optical density ratio of the sample to the negative control) for serum anti-SARS-CoV-2 nucleocapsid IgG antibodies was measured at both visits. We calculated the incidence of seroconversion (defined as RI values ≤1·5 at visit 1 and ≥1·5 at visit 2, and a ratio >2 between the visit 2 and visit 1 RI values) during the study period, as well as incidence rate ratios (IRRs) through cluster-corrected and adjusted Poisson regression models to analyse associations between seroconversion and variables related to sociodemographic characteristics, health access, comorbidities, COVID-19 exposure, protective behaviours, and symptoms. FINDINGS: 2496 DETECTCoV-19 cohort participants returned for a follow-up visit between Oct 19 and Nov 27, 2020, of whom 204 reported having COVID-19 before the first visit and 24 had no data regarding previous disease status. 559 participants were seropositive for anti-SARS-CoV-2 nucleocapsid IgG antibodies at baseline. Of the remaining 1709 participants who were seronegative at baseline, 71 did not meet the criteria for seroconversion and were excluded from the analyses. Among the remaining 1638 participants who were seronegative at baseline, 214 showed seroconversion at visit 2. The seroconversion incidence was 13·06% (95% CI 11·52-14·79) overall and 6·78% (5·61-8·10) for symptomatic seroconversion, over a median follow-up period of 57 days (IQR 54-61). 48·1% of seroconversion events were estimated to be asymptomatic. The sample had higher proportions of affluent and higher-educated people than those reported for the Manaus city population. In the fully adjusted and corrected model, risk factors for seroconversion before visit 2 were having a COVID-19 case in the household (IRR 1·49 [95% CI 1·21-1·83]), not wearing a mask during contact with a person with COVID-19 (1·25 [1·09-1·45]), relaxation of physical distancing (1·31 [1·05-1·64]), and having flu-like symptoms (1·79 [1·23-2·59]) or a COVID-19 diagnosis (3·57 [2·27-5·63]) between the first and second visits, whereas working remotely was associated with lower incidence (0·74 [0·56-0·97]). INTERPRETATION: An intense infection transmission period preceded the second wave of COVID-19 in Manaus. Several modifiable behaviours increased the risk of seroconversion, including non-compliance with non-pharmaceutical interventions measures such as not wearing a mask during contact, relaxation of protective measures, and non-remote working. Increased testing in high-transmission areas is needed to provide timely information about ongoing transmission and aid appropriate implementation of transmission mitigation measures. FUNDING: Ministry of Education, Brazil; Fundação de Amparo à Pesquisa do Estado do Amazonas; Pan American Health Organization (PAHO)/WHO.

The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the spike protein.

Mutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. Importantly, we detected the community transmission of different P.1 lineages bearing NTD indels ∆69-70 (which can impact several SARS-CoV-2 diagnostic protocols), ∆144 and ins214ANRN, and a new VOI N.10 derived from the B.1.1.33 lineage carrying three NTD deletions (∆141-144, ∆211, and ∆256-258). These findings support that the ongoing widespread transmission of SARS-CoV-2 in Brazil generates new viral lineages that might be more resistant to antibody neutralization than parental variants of concern.

The emergence of novel SARS-CoV-2 variant P.1 in Amazonas (Brazil) was temporally associated with a change in the age and sex profile of COVID-19 mortality: A population based ecological study.

BACKGROUND: Since the end of 2020, there has been a great deal of international concern about the variants of SARS-COV-2 B.1.1.7, identified in the United Kingdom; B.1.351 discovered in South Africa and P.1, originating from the Brazilian state of Amazonas. The three variants were associated with an increase in transmissibility and worsening of the epidemiological situation in the places where they expanded. The lineage B.1.1.7 was associated with the increase in case fatality rate in the United Kingdom. There are still no studies on the case fatality rate of the other two variants. The aim of this study was to analyze the mortality profile before and after the emergence of the P.1 strain in the Amazonas state. METHODS: We analyzed data from the Influenza Epidemiological Surveillance Information System, SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe), comparing two distinct epidemiological periods: during the peak of the first wave, between April and May 2020, and in January 2021 (the second wave), the month in which the new variant came to predominate. We calculated mortality rates, overall case fatality rate and case fatality rate among hospitalized patients; all rates were calculated by age and gender and 95% confidence intervals (95% CI) were determined. FINDINGS: We observed that in the second wave there were a higher incidence and an increase in the proportion of cases of COVID-19 in the younger age groups. There was also an increase in the proportion of women among Severe Acute Respiratory Infection (SARI) cases from 40% (2,709) in the first wave to 47% (2,898) in the second wave and in the proportion of deaths due to COVID-19 between the two periods varying from 34% (1,051) to 47% (1,724), respectively. In addition, the proportion of deaths among people between 20 and 59 years old has increased in both sexes. The case fatality rate among those hospitalized in the population between 20 and 39 years old during the second wave was 2.7 times the rate observed in the first wave (female rate ratio = 2.71; 95% CI: 1.9-3.9], p <0.0001; male rate ratio = 2.70, 95%CI:2.0-3.7), and in the general population the rate ratios were 1.15 (95% CI: 1.1-1.2) in females and 0.78 (95% CI: 0.7-0.8) in males]. INTERPRETATION: Based on this prompt analysis of the epidemiological scenario in the Amazonas state, the observed changes in the pattern of mortality due to COVID-19 between age groups and gender simultaneously with the emergence of the P.1 strain suggest changes in the pathogenicity and virulence profile of this new variant. Further studies are needed to better understanding of SARS-CoV-2 variants profile and their impact for the health population. FUNDING: There was no funding for this study.

Spread of Gamma (P.1) sub-lineages carrying Spike mutations close to the furin cleavage site and deletions in the N-terminal domain drives ongoing transmission of SARS-CoV-2 in Amazonas, Brazil

The Amazonas was one of the most heavily affected Brazilian states by the COVID-19 epidemic. Despite a large number of infected people, particularly during the second wave associated with the spread of the Variant of Concern (VOC) Gamma (lineage P.1), SARS-CoV-2 continues to circulate in the Amazonas. To understand how SARS-CoV-2 persisted in a human population with a high immunity barrier, we generated 1,188 SARS-CoV-2 whole-genome sequences from individuals diagnosed in the Amazonas state from 1st January to 6th July 2021, of which 38 were vaccine breakthrough infections. Our study reveals a sharp increase in the relative prevalence of Gamma plus (P.1+) variants, designated as Pango Lineages P.1.3 to P.1.6, harboring two types of additional Spike changes: deletions in the N-terminal (NTD) domain (particularly{Delta} 144 or{Delta} 141-144) associated with resistance to anti-NTD neutralizing antibodies or mutations at the S1/S2 junction (N679K or P681H) that probably enhance the binding affinity to the furin cleavage site, as suggested by our molecular dynamics simulations. As lineages P.1.4 (S:N679K) and P.1.6 (S:P681H) expanded (Re > 1) from March to July 2021, the lineage P.1 declined (Re < 1) and the median Ct value of SARS-CoV-2 positive cases in Amazonas significantly decreases. Still, we found no overrepresentation of P.1+ variants among breakthrough cases of fully vaccinated patients (71%) in comparison to unvaccinated individuals (93%). This evidence supports that the ongoing endemic transmission of SARS-CoV-2 in the Amazonas is driven by the spread of new local Gamma/P.1 sub-lineages that are more transmissible, although not more efficient to evade vaccine-elicited immunity than the parental VOC. Finally, as SARS-CoV-2 continues to spread in human populations with a declining density of susceptible hosts, the risk of selecting new variants with higher infectivity are expected to increase.

Effectiveness of CoronaVac among healthcare workers in the setting of high SARS-CoV-2 Gamma variant transmission in Manaus, Brazil: A test-negative case-control study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported. METHODS: We performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection. FINDINGS: For the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case-control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate. INTERPRETATION: Evidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented. FUNDING: Fundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus; Fundação de Vigilância em Saúde do Amazonas.

SARS-CoV-2 seroprevalence and associated factors in Manaus, Brazil: baseline results from the DETECTCoV-19 cohort study.

BACKGROUND: Manaus, located in the Brazilian rainforest, has experienced two health system collapses due to the coronavirus disease 2019 (COVID-19) pandemic. However, little is known about which groups among the general population have been most affected. METHODS: A convenience sampling strategy via online advertising recruited 3046 adults between 19 August 2020 and 2 October 2020. Sociodemographic characteristics, COVID-19-related symptoms, COVID-19 testing, self-medication and prescribed medications were recorded. Serum anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid immunoglobulin G antibodies were measured with an enzyme-linked immunosorbent assay. Prevalence ratios (PR) were obtained using cluster-corrected and adjusted Poisson's regression models. RESULTS: A crude positivity rate among asymptomatic and symptomatic individuals was estimated at 29.10%, with maximum possible seroprevalence of 44.82% corrected by test characteristics and an antibody decay rate of 32.31%. Regression models demonstrated a strong association towards marginalized low-income and vulnerable residents with limited access to health care. The presence of a COVID-19 case [PR 1.39, 95% confidence interval (CI) 1.24-1.57] or death (PR 2.14, 95% CI 1.74-2.62) in a household greatly increased the risk of other household members acquiring infection. The seroprevalence of SARS-CoV-2 was higher among those who self-medicated to prevent infection (PR 1.36, 95% CI 1.27-1.46). CONCLUSIONS: Disproportionate socio-economic disparity was observed among the study participants. The syndemic nature of COVID-19 in the Amazon region needs differential policies and urgent solutions to control the ongoing pandemic.

COVID-19 in Amazonas, Brazil, was driven by the persistence of endemic lineages and P.1 emergence.

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.

A Potential SARS-CoV-2 Variant of Interest (VOI) Harboring Mutation E484K in the Spike Protein Was Identified within Lineage B.1.1.33 Circulating in Brazil.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Brazil was dominated by two lineages designated as B.1.1.28 and B.1.1.33. The two SARS-CoV-2 variants harboring mutations at the receptor-binding domain of the Spike (S) protein, designated as lineages P.1 and P.2, evolved from lineage B.1.1.28 and are rapidly spreading in Brazil. Lineage P.1 is considered a Variant of Concern (VOC) because of the presence of multiple mutations in the S protein (including K417T, E484K, N501Y), while lineage P.2 only harbors mutation S:E484K and is considered a Variant of Interest (VOI). On the other hand, epidemiologically relevant B.1.1.33 deriving lineages have not been described so far. Here we report the identification of a new SARS-CoV-2 VOI within lineage B.1.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021. This VOI displayed four non-synonymous lineage-defining mutations (NSP3:A1711V, NSP6:F36L, S:E484K, and NS7b:E33A) and was designated as lineage N.9. The VOI N.9 probably emerged in August 2020 and has spread across different Brazilian states from the Southeast, South, North, and Northeast regions.

Effectiveness of CoronaVac in the setting of high SARS-CoV-2 P.1 variant transmission in Brazil: A test-negative case-control study

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported. MethodsWe performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection. FindingsFor the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case- control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate. InterpretationEvidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented. FundingFundacao Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for articles published from inception of the pandemic until April 3, 2021, with no language restrictions, using the search terms "P.1" AND "vaccine" AND "SARS-CoV-2". Additionally, we searched for "CoronaVac" AND "SARS-CoV-2". Early studies have found plasma from convalescent COVID-19 patients and sera from vaccinated individuals have reduced neutralisation of the SARS-CoV-2 variant, Gamma or P.1, compared with strains isolated earlier in the pandemic. Pfizer BNT162b2 mRNA, Oxford-AstraZeneca ChAdOx1, and CoronaVac are the only vaccines for which such data has been published to date. No studies reported effectiveness of any vaccine on reducing the risk of infection or disease among individuals exposed to P.1 or in settings of high P.1 transmission. Added value of this studyThis study finds that vaccination with CoronaVac was 49.4% (95% CI 13.2 to 71.9) effective at preventing COVID-19 in a setting with likely high prevalence of the Gamma Variant of Concern. However, an analysis of effectiveness by dose was underpowered and failed to find significant effectiveness of the two-dose schedule of CoronaVac (estimated VE 37.1%, 95% CI -53.3 to 74.2). Implications of all the available evidenceThese findings are suggestive for the effectiveness of CoronaVac in healthcare workers in the setting of widespread P.1 transmission but must be strengthened by observational studies in other settings and populations. Based on this evidence, there is a need to implement sustained non-pharmaceutical interventions even as vaccination campaigns continue.

The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the Spike protein

Mutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the SARS-CoV-2 Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. These findings support that the ongoing widespread transmission of SARS-CoV-2 in Brazil is generating new viral lineages that might be more resistant to neutralization than parental variants of concern.

The emergence of novel SARS-CoV-2 variant P.1 in Amazonas (Brazil) was temporally associated with a change in the age and gender profile of COVID-19 mortality / A emergência da nova variante P.1 do SARS-CoV-2 no Amazonas (Brasil) foi temporalmente associada a uma mudança no perfil da mortalidade devido a COVID-19, segundo sexo e idade

Background Since the end of 2020, there has been a great deal of international concern about the variants of SARS-COV-2 B.1.1.7, identified in the United Kingdom; B.1.351 discovered in South Africa and P.1, originating from the Brazilian state of Amazonas. The three variants were associated with an increase in transmissibility and worsening of the epidemiological situation in the places where they expanded. The lineage B.1.1.7 was associated with the increase in case fatality rate in the United Kingdom. There are still no studies on the case fatality rate of the other two variants. The aim of this study was to analyze the mortality profile before and after the emergence of the P.1 strain in the Amazonas state. Methods We analyzed data from the Influenza Epidemiological Surveillance Information System, SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe), comparing two distinct epidemiological periods: during the peak of the first wave, between April and May 2020, and in January 2021 (the second wave), the month in which the new variant came to predominate. We calculated mortality rates, overall case fatality rate and case fatality rate among hospitalized patients; all rates were calculated by age and gender and 95% confidence intervals (95% CI) were determined. Findings We observed that in the second wave there were a higher incidence and an increase in the proportion of cases of COVID-19 in the younger age groups. There was also an increase in the proportion of women among Severe Acute Respiratory Infection (SARI) cases from 40% (2,709) in the first wave to 47% (2,898) in the second wave and in the proportion of deaths due to COVID-19 between the two periods varying from 34% (1,051) to 47% (1,724), respectively. In addition, the proportion of deaths among people between 20 and 59 years old has increased in both sexes. The case fatality rate among those hospitalized in the population between 20 and 39 years old during the second wave was 2.7 times the rate observed in the first wave (female rate ratio = 2.71; 95% CI: 1.9-3.9], p <0.0001; male rate ratio = 2.70, 95%CI:2.0-3.7), and in the general population the rate ratios were 1.15 (95% CI: 1.1-1.2) in females and 0.78 (95% CI: 0.7-0.8) in males]. Interpretation Based on this prompt analysis of the epidemiological scenario in the Amazonas state, the observed changes in the pattern of mortality due to COVID-19 between age groups and gender simultaneously with the emergence of the P.1 strain suggest changes in the pathogenicity and virulence profile of this new variant. Further studies are needed to better understanding of SARS-CoV-2 variants profile and their impact for the health population.

Introdução Desde o final de 2020 tem havido grande preocupação internacional com as variantes do SARS-COV-2: B.1.1.7, identificada no Reino Unido; B.1.351, descoberta na África do Sul e P.1, que emergiu inicialmente estado brasileiro do Amazonas. As três variantes foram associadas a aumento na transmissibilidade e piora da situação epidemiológica nos locais onde se expandiram. A linhagem B.1.1.7 foi associada ao aumento da taxa de letalidade no Reino Unido. Ainda não existem estudos conclusivos sobre letalidade das outras duas variantes. O objetivo deste estudo foi analisar o perfil de mortalidade antes e depois da emergência da linhagem P.1 no Amazonas. Métodos Analisamos os dados do sistema nacional de vigilância epidemiológica, comparando dois momentos epidemiológicos distintos: durante o pico da primeira onda, entre abril e maio de 2020, e em janeiro de 2021, mês em que a nova variante passou a predominar. Calculamos as taxas de mortalidade, letalidade e letalidade entre pacientes internados, todas as taxas foram calculadas por idade e por sexo e determinados os intervalos de confiança de 95%. Achados Observamos que na segunda onda houve maior incidência e aumento na proporção de casos de COVID-19 nas faixas etárias mais jovens. Observou-se, também, um aumento na proporção de mulheres entre os casos de SARI de 40% (2.709) na primeira onda para 47% (2.898) na segunda onda e entre mortes por COVID-19 de 34% (1,051) para 47% (1.724), respectivamente. Além disso, a proporção de mortes entre 20 e 59 anos aumentou em ambos os sexos. A letalidade entre os hospitalizados na população entre 20 e 39 anos durante a segunda onda foi 2.7 vezes a primeira onda [razão de taxas sexo feminino=2,71; CI(95%)=1,9-3,9], p<0.0001; razão de taxas sexo masculino=2.70(2.0-3.7)), na população geral as razões de taxa foram 1,15(1,1-1,2) no sexo feminino e 0,78(0,7-0,8) no sexo masculino. Interpretação Observamos mudanças no padrão de mortalidade por COVID-19 entre as faixas etárias e sexo simultaneamente à emergência da linhagem P.1, sugerindo mudanças nos perfis de patogenicidade e virulência, novos estudos são necessários para melhor compreensão das variantes do SARS-CoV-2 e suas consequências na saúde da população.

Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2

Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD impact neutralisation. Monoclonal antibody 222 neutralises all three variants despite interacting with two of the ACE2 binding site mutations, we explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.

Identification of a novel SARS-CoV-2 P.1 sub-lineage in Brazil provides new insights about the mechanisms of emergence of variants of concern.

One of the most remarkable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) features is the significant number of mutations they acquired. However, the specific factors that drove the emergence of such variants since the second half of 2020 are not fully resolved. In this study, we describe a new SARS-CoV-2 P.1 sub-lineage circulating in Brazil, denoted here as Gamma-like-II, that as well as the previously described lineage Gamma-like-I shares several lineage-defining mutations with the VOC Gamma. Reconstructions of ancestor sequences support that most lineage-defining mutations of the Spike (S) protein, including those at the receptor-binding domain (RBD), accumulated at the first P.1 ancestor. In contrast, mutations outside the S protein were mostly fixed at subsequent steps. Our evolutionary analyses estimate that P.1-ancestral strains carrying RBD mutations of concern probably circulated cryptically in the Amazonas for several months before the emergence of the VOC Gamma. Unlike the VOC Gamma, the other P.1 sub-lineages displayed a much more restricted dissemination and accounted for a low fraction (<2 per cent) of SARS-CoV-2 infections in Brazil in 2021. The stepwise diversification of lineage P.1 through multiple inter-host transmissions is consistent with the hypothesis that partial immunity acquired from natural SARS-CoV-2 infections in heavily affected regions might have been a major driving force behind the natural selection of some VOCs. The lag time between the emergence of the P.1 ancestor and the expansion of the VOC Gamma and the divergent epidemic trajectories of P.1 sub-lineages support a complex interplay between the emergence of mutations of concern and viral spread in Brazil.