Molecular epidemiology of the SARS-CoV-2 variant Omicron BA.2 sub-lineage in Denmark, 29 November 2021 to 2 January 2022

Following emergence of the SARS-CoV-2 variant Omicron in November 2021, the dominant BA.1 sub-lineage was replaced by the BA.2 sub-lineage in Denmark. We analysed the first 2,623 BA.2 cases from 29 November 2021 to 2 January 2022. No epidemiological or clinical differences were found between individuals infected with BA.1 versus BA.2. Phylogenetic analyses showed a geographic east-to-west transmission of BA.2 from the Capital Region with clusters expanding after the Christmas holidays. Mutational analysis shows distinct differences between BA.1 and BA.2.     

Tracking the progressive spread of the SARS-CoV-2 Omicron variant in Italy,December 2021 to January 2022

BackgroundThe SARS-CoV-2 variant of concern Omicron was first detected in Italy in November 2021.AimTo comprehensively describe Omicron spread in Italy in the 2 subsequent months and its impact on the overall SARS-CoV-2 circulation at population level.MethodsWe analyse data from four genomic surveys conducted across the country between December 2021 and January 2022. Combining genomic sequencing results with epidemiological records collated by the National Integrated Surveillance System, the Omicron reproductive number and exponential growth rate are estimated, as well as SARS-CoV-2 transmissibility.ResultsOmicron became dominant in Italy less than 1 month after its first detection, representing on 3 January 76.9–80.2% of notified SARS-CoV-2 infections, with a doubling time of 2.7–3.3 days. As of 17 January 2022, Delta variant represented < 6% of cases. During the Omicron expansion in December 2021, the estimated mean net reproduction numbers respectively rose from 1.15 to a maximum of 1.83 for symptomatic cases and from 1.14 to 1.36 for hospitalised cases, while remaining relatively stable, between 0.93 and 1.21, for cases needing intensive care. Despite a reduction in relative proportion, Delta infections increased in absolute terms throughout December contributing to an increase in hospitalisations. A significant reproduction numbers’ decline was found after mid-January, with average estimates dropping below 1 between 10 and 16 January 2022.ConclusionEstimates suggest a marked growth advantage of Omicron compared with Delta variant, but lower disease severity at population level possibly due to residual immunity against severe outcomes acquired from vaccination and prior infection.     

SARS-CoV-2 molecular epidemiology in Slovenia,January to September 2021

BackgroundSequencing of SARS-CoV-2 PCR-positive samples was introduced in Slovenia in January 2021. Our surveillance programme comprised three complementary schemes: (A) non-targeted sequencing of at least 10% of samples, (B) sequencing of samples positive after PCR screening for variants of concern (VOC) and (C) sequencing as per epidemiological indication.AimWe present the analysis of cumulative data of the non-targeted surveillance of SARS-CoV-2 and variant-dependent growth kinetics for the five most common variants in Slovenia for the first 9 months of 2021.MethodsSARS-CoV-2 PCR-positive samples, from January to September 2021, were selected for sequencing according to the national surveillance plan. Growth kinetics studies were done on Vero E6 cells.ResultsAltogether 15,175 genomes were sequenced and 64 variants were detected, of which three successively prevailed. Variant B.1.258.17 was detected in ca 80% of samples in January and was replaced, within 9 weeks, by the Alpha variant. The number of cases decreased substantially during the summer of 2021. However, the introduction of the Delta variant caused a fourth wave and completely outcompeted other variants. Other VOC were only detected in small numbers. Infection of Vero E6 cells showed higher replication rates for the variants Alpha and Delta, compared with B.1.258.17, B.1.258, and B.1.1.70, which dominated in Slovenia before the introduction of the Alpha and Delta variants.ConclusionInformation on SARS-CoV-2 variant diversity provided context to the epidemiological data of PCR-positive cases, contributed to control of the initial spread of known VOC and influenced epidemiological measures.     

Risk reduction of hospitalisation and severe disease in vaccinated COVID-19 cases during the SARS-CoV-2 variant Omicron BA.1-predominant period,Navarre, Spain,January to March 2022

BackgroundAs COVID-19 vaccine effectiveness against SARS-CoV-2 infection was lower for cases of the Omicron vs the Delta variant, understanding the effect of vaccination in reducing risk of hospitalisation and severe disease among COVID-19 cases is crucial.AimTo evaluate risk reduction of hospitalisation and severe disease in vaccinated COVID-19 cases during the Omicron BA.1-predominant period in Navarre, Spain.MethodsA case-to-case comparison included COVID-19 epidemiological surveillance data in adults ≥ 18 years from 3 January–20 March 2022. COVID-19 vaccination status was compared between hospitalised and non-hospitalised cases, and between severe (intensive care unit admission or death) and non-severe cases using logistic regression models.ResultsAmong 58,952 COVID-19 cases, 565 (1.0%) were hospitalised and 156 (0.3%) were severe. The risk of hospitalisation was reduced within the first 6 months after full COVID-19 vaccination (complete primary series) (adjusted odds ratio (aOR): 0.06; 95% CI: 0.04–0.09) and after 6 months (aOR: 0.16; 95% CI: 0.12–0.21; p_comparison < 0.001), as well as after a booster dose (aOR: 0.06: 95% CI: 0.04–0.07). Similarly, the risk of severe disease was reduced (aOR: 0.13, 0.18, and 0.06, respectively). Compared with cases fully vaccinated 6 months or more before a positive test, those who had received a booster dose had lower risk of hospitalisation (aOR: 0.38; 95% CI: 0.28–0.52) and severe disease (aOR: 0.38; 95% CI: 0.21–0.68).ConclusionsFull COVID-19 vaccination greatly reduced the risk of hospitalisation and severe outcomes in COVID-19 cases with the Omicron variant, and a booster dose improved this effect in people aged over 65 years.     

SARS-CoV-2 variant spike and accessory gene mutations alter pathogenesis

The ongoing COVID-19 pandemic is a major public health crisis. Despite the development and deployment of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pandemic persists. The continued spread of the virus is largely driven by the emergence of viral variants, which can evade the current vaccines through mutations in the spike protein. Although these differences in spike are important in terms of transmission and vaccine responses, these variants possess mutations in the other parts of their genome that may also affect pathogenesis. Of particular interest to us are the mutations present in the accessory genes, which have been shown to contribute to pathogenesis in the host through interference with innate immune signaling, among other effects on host machinery. To examine the effects of accessory protein mutations and other nonspike mutations on SARS-CoV-2 pathogenesis, we synthesized both viruses possessing deletions in the accessory genes as well as viruses where the WA-1 spike is replaced by each variant spike gene in a SARS-CoV-2/WA-1 infectious clone. We then characterized the in vitro and in vivo replication of these viruses and compared them to both WA-1 and the full variant viruses. Our work has revealed that the accessory proteins contribute to SARS-CoV-2 pathogenesis and the nonspike mutations in variants can contribute to replication of SARS-CoV-2 and pathogenesis in the host. This work suggests that while spike mutations may enhance receptor binding and entry into cells, mutations in accessory proteins may alter clinical disease presentation.

In December 2019, a cluster of viral pneumonia cases was observed in Wuhan, Hubei Province, China (1). The etiologic agent of this infection was found to be a novel coronavirus that we now call severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (2). By early 2020, the virus was rapidly spreading, leading to infections on all seven continents and in every country around the world. There have since been over 550 million cases and six million deaths from this virus (3). Despite the rapid development and deployment of vaccines, the pandemic persists.SARS-CoV-2 is a single-stranded positive-sense RNA virus that is 79% identical in sequence to SARS-CoV-1, the virus responsible for localized epidemic outbreaks beginning in February 2003 (4). The genome of this and other beta coronaviruses is composed of Open Reading Frames (ORFs), which are functionally divided between replicase proteins, structural proteins, and accessory proteins, the latter of which are unique to each CoV species (5, 6). From the 5′ to the 3′ end, the virus encodes the replicase (ORF1a/b) and the four ORFS for the structural proteins spike (S), envelope (E), membrane (M), and nucleocapsid (N). The replicase is responsible for encoding 16 nonstructural proteins that compose the replicative machinery of the virus. Additionally, interspersed with the structural proteins at the 3′ end of the genome are a variety of accessory ORFs. The accessory ORFs encode proteins that are not essential for viral replication in vitro but contribute to viral pathogenesis. The accessory ORFs of SARS-CoV-2 are very similar to those of SARS-CoV-1, and many of the functions of these ORFs have been inferred based on the previously identified functions of the SARS-CoV-1 accessory ORFs (5).The functions of the accessory ORFs of SARS-CoV-2 involve modulation of several different host pathways including antagonism of the innate immune response. For example, SARS-CoV-2 ORF3b has been shown to antagonize interferon (IFN) signaling, and ORF7a has been shown to interfere with the IFN-stimulated gene (ISG) BST2 (7–9). SARS-CoV-2 ORF6 also participates in this antagonism of the innate immune response, as it has been shown to antagonize the IFN-induced nuclear translocation of STAT1, resulting in the reduced expression of ISGs (10). While ORF3a, ORF6, and ORF7a have been shown to be antagonists of the innate immune system, SARS-CoV-2 ORF8 has been shown to act as an agonist for the interleukin 17 (IL-17) receptor, functionally stimulating receptor signaling (11).The continuation of the COVID-19 pandemic is largely due to the emergence of mutated strains, or “variants,” of SARS-CoV-2. The variants differ most notably in the sequence of their spike proteins, which bind to the receptor angiotensin-converting enzyme 2 (ACE2) to allow for internalization of the virus. As the spike protein is the immunodominant antigen, the emergence of variants has raised concerns regarding the breadth of protection of the SARS-CoV-2 vaccines. However, it is important to note that many of the variants of SARS-CoV-2 possess mutations in one or more of the accessory proteins. The impact of such mutations outside of the spike protein on the pathogenesis of these variants remains understudied.To elucidate the role of the accessory proteins of SARS-CoV-2 in pathogenesis, we developed a synthetic genomics assembly approach based on transformation-associated recombination (TAR) in yeast for the creation of infectious clones of SARS-CoV-2 (12–15). We then synthesized deletion viruses of ORFs 3a/3b, 6, 7a/7b, and 8 in the prototype SARS-CoV-2 (isolate USA/-WA1/2020 or WA-1) strain of SARS-CoV-2. We then investigated the replicative fitness of these viruses in vitro before proceeding to characterization of the effect of these accessory deletions on pathogenesis in a murine model. To begin to characterize the impact of naturally occurring accessory mutations and nonspike mutations found in the variants on the pathogenesis of SARS-CoV-2, we developed recombinant variant spike proteins in the WA-1 backbone (B.1.1.7, B.1.351, and P.1). We then compared the replicative fitness in vitro of these recombinant viruses to the parent variants and characterized differences in pathogenesis in a mouse model.     

Estimating the serial intervals of SARS-CoV-2 Omicron BA.4, BA.5, and BA.2.12.1 variants in Hong Kong

Empirical evidence on the epidemiological characteristics of the emerged SARS-CoV-2 variants could shed light on the transmission potential of the virus and strategic outbreak control planning. In this study, by using contact tracing data collected during an Omicron-predominant epidemic phase in Hong Kong, we estimated the mean serial interval of SARS-CoV-2 Omicron BA.4, BA.5, and BA.2.12.1 variants at 2.8 days (95% credible interval [CrI]: 1.5, 6.7), 2.7 days (95% CrI: 2.1, 3.6), and 4.4 days (95% CrI: 2.6, 7.5), respectively, with adjustment for right truncation and sampling bias. The short serial interval for the current circulating variant indicated that outbreak mitigations through contact tracing and case isolation would be quite challenging.     

In-Silico Analysis of Monoclonal Antibodies against SARS-CoV-2 Omicron

Omicron was designated by the WHO as a VOC on 26 November 2021, only 4 days after its sequence was first submitted. However, the impact of Omicron on current antibodies and vaccines remains unknown and evaluations are still a few weeks away. We analysed the mutations in the Omicron variant against epitopes. In our database, 132 epitopes of the 120 antibodies are classified into five groups, namely NTD, RBD-1, RBD-2, RBD-3, and RBD-4. The Omicron mutations impact all epitopes in NTD, RBD-1, RBD-2, and RBD-3, with no antibody epitopes spared by these mutations. Only four out of 120 antibodies may confer full resistance to mutations in the Omicron spike, since all antibodies in these three groups contain one or more epitopes that are affected by these mutations. Of all antibodies under EUA, the neutralisation potential of Etesevimab, Bamlanivimab, Casirivimab, Imdevima, Cilgavimab, Tixagevimab, Sotrovimab, and Regdanvimab might be dampened to varying degrees. Our analysis suggests the impact of Omicron on current therapeutic antibodies by the Omicron spike mutations may also apply to current COVID-19 vaccines.     

Impact of the Omicron variant on SARS-CoV-2 reinfections in France,March 2021 to February 2022

Since the first reports in summer 2020, SARS-CoV-2 reinfections have raised concerns about the immunogenicity of the virus, which will affect SARS-CoV-2 epidemiology and possibly the burden of COVID-19 on our societies in the future. This study provides data on the frequency and characteristics of possible reinfections, using the French national COVID-19 testing database. The Omicron variant had a large impact on the frequency of possible reinfections in France, which represented 3.8% of all confirmed COVID-19 cases since December 2021.     

Structural basis for mouse receptor recognition by SARS-CoV-2 omicron variant

The sudden emergence and rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant has raised questions about its animal reservoir. Here, we investigated receptor recognition of the omicron’s receptor-binding domain (RBD), focusing on four of its mutations (Q493R, Q498R, N501Y, and Y505H) surrounding two mutational hotspots. These mutations have variable effects on the RBD’s affinity for human angiotensin-converting enzyme 2 (ACE2), but they all enhance the RBD’s affinity for mouse ACE2. We further determined the crystal structure of omicron RBD complexed with mouse ACE2. The structure showed that all four mutations are viral adaptations to mouse ACE2: three of them (Q493R, Q498R, and Y505H) are uniquely adapted to mouse ACE2, whereas the other one (N501Y) is adapted to both human ACE2 and mouse ACE2. These data reveal that the omicron RBD was well adapted to mouse ACE2 before omicron started to infect humans, providing insight into the potential evolutionary origin of the omicron variant.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant emerged abruptly and spread rapidly around the globe (1–4). Tracking the animal reservoir of SARS-CoV-2 and its variants is important for understanding the current COVID-19 pandemic and preventing future pandemics. Speculations about the source of the omicron variant are abundant, yet experimental evidence has been scarce (5). The interactions between the receptor-binding domain (RBD) of coronavirus spike proteins and their host receptor are among the best systems for understanding coronavirus evolution (6, 7). Both SARS-CoV-2 and closely related SARS-CoV-1 recognize human angiotensin-converting enzyme 2 (ACE2) as their receptor (8–10). Previous research on the receptor recognition of SARS-CoV-1 has provided insight into the animal origin of SARS-CoV-1 (11–15). The RBD of the original SARS-CoV-2 strain (i.e., prototypic RBD) differs from the RBD of a bat coronavirus by only a few residues, supporting a bat origin of the prototypic RBD (16). The omicron RBD (strain BA.2) differs from the prototypic RBD by 16 residues, seven of which are located in the receptor-binding motif (RBM) that directly contacts ACE2 (3). To recover the evolutionary traces left by these RBM mutations, this study compared the structural adaptations of the omicron RBD to ACE2 from human and mouse, two possible sources of omicron (5).Three virus-binding hotspots have been identified at the interfaces between SARS-CoV-2 RBD and human ACE2 (hACE2) and between SARS-CoV-1 RBD and hACE2 (14, 17, 18). These hotspots center on Lys31 in hACE2 (i.e., hotspot-31), Lys353 in hACE2 (i.e., hotspot-353), and a receptor-binding ridge in the viral RBD (i.e., hotspot-ridge) (Fig. 1A). These virus-binding hotspots are also mutational hotspots for SARS-CoV-1: all of the RBM mutations occurred around the hotspots and impacted the structural stability of the hotspots (13, 14). Establishment of the “hotspots” concept was instrumental in determining the molecular mechanisms by which SARS-CoV-1 was transmitted from palm civets to humans (11–15). The RBM mutations in the SARS-CoV-2 omicron variant are also around the hotspots (Fig. 1A). Curiously, only a few of these omicron mutations enhance the RBD’s affinity for hACE2, while some other mutations reduce it (Fig. 1B) (17). Structural details of the interface between the omicron RBM (strain BA.1) and hACE2 elucidated the role of each of these mutations in binding hACE2 (17). The omicron mutations that reduce the RBD’s affinity for hACE2 are structurally incompatible with hACE2, raising questions about what other species may have mediated the evolution of omicron.Open in a separate windowFig. 1.Binding interactions between SARS-CoV-2 RBD (from prototypic strain or omicron strain) and ACE2 (from human or mouse). (A) Structure of the interface between prototypic RBM and hACE2 (PDB ID: 6VW1). RBM is in magenta. hACE2 is in green. RBD residues that have undergone mutations from the prototypic strain to the omicron variant (strain BA.2) are shown as sticks. Three mutational hotspots are highlighted: hotspot-353 centers on Lys353 in hACE2, hotspot-31 centers on Lys31 in hACE2, and hotspot-ridge centers on the receptor-binding ridge in hACE2. (B and C) SPR assay for the binding of RBD (from prototypic strain or omicron strain) to ACE2 (from human or mouse). ACE2-Fc was coated to a protein A chip in a fixed direction, and individual RBDs flowed through. Data in B are from one of our recent studies (17), except that the omicron variant (strain BA.2) in this study replaced strain BA.1 in the previous study. Data in C are from the current study. The data in B and C are presented as mean ± SEM (n = 3 or n = 4) on a log scale. A Student’s two-tailed t test was performed to analyze the statistical difference between the RBD on the Left in either panel and each of the other RBDs in the same panel; the results are labeled on top of each bar. The statistical difference between the R493Q mutation and the N477S/R493Q double mutations was also analyzed in C; the result was labeled between the two bars. The horizontal dashed lines represent the measurements for the prototypic RBD in B or the omicron RBD in C and are used for comparison with other measurements in the respective panel. ***P < 0.001; **P < 0.01; *P < 0.05. n.s., statistically not significant, N.D., not detected.In this study, we provide biochemical and structural evidence demonstrating that the omicron mutations are better adapted to mouse ACE2 (mACE2) than to hACE2, suggesting that mice mediated the onset of the omicron variant. Our study helps clarify the animal reservoir of the omicron variant and contributes to the understanding of SARS-CoV-2 evolution. The findings may facilitate epidemiological surveillance of SARS-CoV-2 in animals to prevent future coronavirus pandemics.     

Analysis of Genomic Characteristics of SARS-CoV-2 in Italy, 29 January to 27 March 2020

We performed next-generation sequencing (NGS), phylogenetic analysis, gene flows, and N- and O-glycosylation prediction on SARS-CoV-2 genomes collected from lab-confirmed cases from different Italian regions. To this end, a total of 111 SARS-CoV-2 genomes collected in Italy between 29 January and 27 March 2020 were investigated. The majority of the genomes belonged to lineage B.1, with some descendant lineages. The gene flow analysis showed that the spread occurred mainly from the north to the center and to the south of Italy, as confirmed by epidemiological data. The mean evolutionary rate estimated here was 8.731 × 10⁻⁴ (95% highest posterior density, HPD intervals 5.809 × 10⁻⁴ to 1.19 × 10⁻³), in line with values reported by other authors. The dated phylogeny suggested that SARS-CoV-2 lineage B.1 probably entered Italy between the end of January and early February 2020. Continuous molecular surveillance is needed to trace virus circulation and evolution.     

SARS-CoV-2 Infections in Vaccinated and Unvaccinated Populations in Camp Lemonnier,Djibouti, from April 2020 to January 2022

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the disparity between developed and developing countries for infectious disease surveillance and the sequencing of pathogen genomes. The majority of SARS-CoV-2 sequences published are from Europe, North America, and Asia. Between April 2020 and January 2022, 795 SARS-CoV-2-positive nares swabs from individuals in the U.S. Navy installation Camp Lemonnier, Djibouti, were collected, sequenced, and analyzed. In this study, we described the results of genomic sequencing and analysis for 589 samples, the first published viral sequences for Djibouti, including 196 cases of vaccine breakthrough infections. This study contributes to the knowledge base of circulating SARS-CoV-2 lineages in the under-sampled country of Djibouti, where only 716 total genome sequences are available at time of publication. Our analysis resulted in the detection of circulating variants of concern, mutations of interest in lineages in which those mutations are not common, and emerging spike mutations.     

Nosocomial outbreak caused by the SARS-CoV-2 Delta variant in a highly vaccinated population,Israel, July 2021

A nosocomial outbreak of SARS-CoV-2 Delta variant infected 42 patients, staff and family members; 39 were fully vaccinated. The attack rate was 10.6% (16/151) among exposed staff and reached 23.7% (23/97) among exposed patients in a highly vaccinated population, 16–26 weeks after vaccination (median: 25 weeks). All cases were linked and traced to one patient. Several transmissions occurred between individuals wearing face masks. Fourteen of 23 patients became severely sick or died, raising a question about possible waning immunity.     

Risk and protective factors for SARS-CoV-2 reinfections,surveillance data,Italy, August 2021 to March 2022

We explored the risk factors associated with SARS-CoV-2 reinfections in Italy between August 2021 and March 2022. Regardless of the prevalent virus variant, being unvaccinated was the most relevant risk factor for reinfection. The risk of reinfection increased almost 18-fold following emergence of the Omicron variant compared with Delta. A severe first SARS-CoV-2 infection and age over 60 years were significant risk factors for severe reinfection.     

Early Genomic,Epidemiological, and Clinical Description of the SARS-CoV-2 Omicron Variant in Mexico City

Omicron is the most mutated SARS-CoV-2 variant—a factor that can affect transmissibility, disease severity, and immune evasiveness. Its genomic surveillance is important in cities with millions of inhabitants and an economic center, such as Mexico City. Results. From 16 November to 31 December 2021, we observed an increase of 88% in Omicron prevalence in Mexico City. We explored the R346K substitution, prevalent in 42% of Omicron variants, known to be associated with immune escape by monoclonal antibodies. In a phylogenetic analysis, we found several independent exchanges between Mexico and the world, and there was an event followed by local transmission that gave rise to most of the Omicron diversity in Mexico City. A haplotype analysis revealed that there was no association between haplotype and vaccination status. Among the 66% of patients who have been vaccinated, no reported comorbidities were associated with Omicron; the presence of odynophagia and the absence of dysgeusia were significant predictor symptoms for Omicron, and the RT-qPCR Ct values were lower for Omicron. Conclusions. Genomic surveillance is key to detecting the emergence and spread of SARS-CoV-2 variants in a timely manner, even weeks before the onset of an infection wave, and can inform public health decisions and detect the spread of any mutation that may affect therapeutic efficacy.     

Characterization of a new SARS-CoV-2 variant that emerged in Brazil

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a key role in viral infectivity. It is also the major antigen stimulating the host''s protective immune response, specifically, the production of neutralizing antibodies. Recently, a new variant of SARS-CoV-2 possessing multiple mutations in the S protein, designated P.1, emerged in Brazil. Here, we characterized a P.1 variant isolated in Japan by using Syrian hamsters, a well-established small animal model for the study of SARS-CoV-2 disease (COVID-19). In hamsters, the variant showed replicative abilities and pathogenicity similar to those of early and contemporary strains (i.e., SARS-CoV-2 bearing aspartic acid [D] or glycine [G] at position 614 of the S protein). Sera and/or plasma from convalescent patients and BNT162b2 messenger RNA vaccinees showed comparable neutralization titers across the P.1 variant, S-614D, and S-614G strains. In contrast, the S-614D and S-614G strains were less well recognized than the P.1 variant by serum from a P.1-infected patient. Prior infection with S-614D or S-614G strains efficiently prevented the replication of the P.1 variant in the lower respiratory tract of hamsters upon reinfection. In addition, passive transfer of neutralizing antibodies to hamsters infected with the P.1 variant or the S-614G strain led to reduced virus replication in the lower respiratory tract. However, the effect was less pronounced against the P.1 variant than the S-614G strain. These findings suggest that the P.1 variant may be somewhat antigenically different from the early and contemporary strains of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged as a novel human pathogen in China at the end of 2019, is responsible for COVID-19, which causes symptoms such as cough and fever, severe pneumonia, and death. The World Health Organization reported that, as of April 2021, ∼130 million cases of COVID-19 and 2.8 million associated deaths have occurred.On January 6, 2021, Japan reported the detection of a new SARS-CoV-2 variant in travelers who arrived at Tokyo airport from Amazonas state, north Brazil (1, 2). This variant, designated P.1, is thought to have emerged in Brazil in November 2020 (3). As of April 2021, the P.1 variant has been detected in 36 countries, with local transmission occurring in 5 countries, including Brazil (4). The P.1 variant differs from early SARS-CoV-2 strains identified in Wuhan, China, by 12 amino acids in the spike (S) protein. S protein plays a key role in viral binding to host cell receptors (i.e., human angiotensin-converting enzyme 2 [hACE2]), and the P.1 variant has three mutations (K417T, E484K, and N501Y) in the receptor-binding domain (RBD). Previous studies suggest that both the E484K and N501Y mutations in the RBD may enhance the binding affinity of the S protein for hACE2 (5–7). In addition, the E484K substitution has been shown to confer resistance to monoclonal and polyclonal neutralizing antibodies in COVID-19 convalescent and postvaccination sera (8–12). However, the replicative capacity, pathogenicity, and antigenicity of the P.1 variant remain largely unknown. To better assess the risk posed by this variant, here we characterized isolates of the P.1 variant of SARS-CoV-2 in Japan in vitro and in vivo.     

COVID-19 Mortality and Social Inequalities: Epidemiological analysis of the emergence and disappearance of the SARS-CoV-2 Kappa variant within a region of British Columbia,Canada

BackgroundThe Kappa variant is designated as a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of interest (VOI). We identified 195 Kappa variant cases in a region of British Columbia, Canada—the largest published cluster in North America.ObjectivesTo describe the epidemiology of the Kappa variant in relation to other circulating SARS-CoV-2 variants of concern (VOC) in the region to determine if the epidemiology of the Kappa variant supports a VOI or VOC status.MethodsClinical specimens testing positive for SARS-CoV-2 collected between March 10 and May 2, 2021, were screened for the detection of known circulating VOCs; approximately 50% of specimens were subsequently selected for whole genome sequencing (WGS). Epidemiological analysis was performed comparing the characteristics of Kappa cases to the main circulating variants in the region (Alpha and Gamma) and to non-VOC/VOI cases.ResultsA total of 2,079 coronavirus disease 2019 (COVID-19) cases were reported in the region during the study period, of which 54% were selected for WGS. The 1,131 sequenced cases were categorized into Kappa, Alpha, Gamma and non-VOC/VOI. While Alpha and Gamma cases were found to have a significantly higher attack rate among household contacts compared to non-VOI/VOC cases, Kappa was not.ConclusionEpidemiological analysis supports the designation of Kappa as a VOI and not a VOC. The Alpha and Gamma variants were found to be more transmissible, explaining their subsequent dominance in the region and the rapid disappearance of the Kappa variant. Variant surveillance strategies should focus on both detection of established VOCs and detection of potential new VOCs.     

Emergence of Two Distinct SARS-CoV-2 Gamma Variants and the Rapid Spread of P.1-like-II SARS-CoV-2 during the Second Wave of COVID-19 in Santa Catarina,Southern Brazil

The western mesoregion of the state of Santa Catarina (SC), Southern Brazil, was heavily affected as a whole by the COVID-19 pandemic in early 2021. This study aimed to evaluate the dynamics of the SARS-CoV-2 virus spreading patterns in the SC state from March 2020 to April 2021 using genomic surveillance. During this period, there were 23 distinct variants, including Beta and Gamma, among which the Gamma and related lineages were predominant in the second pandemic wave within SC. A regionalization of P.1-like-II in the Western SC region was observed, concomitant to the increase in cases, mortality, and the case fatality rate (CFR) index. This is the first evidence of the regionalization of the SARS-CoV-2 transmission in SC and it highlights the importance of tracking the variants, dispersion, and impact of SARS-CoV-2 on the public health systems.     

Seroprevalence of antibodies against SARS-CoV-2 and risk of COVID-19 in Navarre,Spain, May to July 2022

In Navarre, Spain, in May 2022, the seroprevalence of anti-nucleocapsid (N) and anti-spike (S) antibodies of SARS-CoV-2 was 58.9% and 92.7%, respectively. The incidence of confirmed COVID-19 thereafter through July was lower in people with anti-N antibodies (adjusted odds ratio (aOR) = 0.08; 95% confidence interval (CI): 0.05–0.13) but not with anti-S antibodies (aOR = 1.06; 95% CI: 0.47–2.38). Hybrid immunity, including anti-N antibodies induced by natural exposure to SARS-CoV-2, seems essential in preventing Omicron COVID-19 cases.