In an analysis of vaccine breakthrough in over 100 healthcare workers across three centres in India, the Delta variant not only dominates vaccine-breakthrough infections with higher respiratory viral loads compared to non-delta infections (Ct value of 16.5 versus 19), but also generates greater transmission between HCW as compared to B.1.1.7 or B.1.617.1 (p=0.02). In vitro, the Delta variant shows 8 fold approximately reduced sensitivity to vaccine-elicited antibodies compared to wild type Wuhan-1 bearing D614G.

Several fast-spreading variants of SARS-CoV-2 have become the dominant circulating strains in the COVID-19 pandemic. We report here cryo-EM structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Amino acid substitutions in the B.1.1.7 protein increase the accessibility of its receptor binding domain and also the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2). The enhanced receptor engagement may account for the increased transmissibility.

Data about APOE expression levels was obtained from the Genotype-Tissue Expression Project and the allele frequencies of APOE variants was acquired from the populations included in the phase 3 release of the 1000 Genomes Project. A total of 128 variants showed a significant impact on the APOE expression in lung tissues (p < 0.0001). Linkage Disequilibrium analysis revealed that 98 variants were closely grouped into seven distinct haplotype blocks, of which six were composed of variants that significantly decrease APOE gene expression in the lungs.

SARS-CoV-2 variants with multiple spike mutations enable increased transmission and antibody resistance. Here, we combine cryo-EM, binding and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans, and others that originated and spread in human populations. All variants showed increased ACE2 receptor binding and increased propensity for RBD up states.

Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOC) and had a median Ct of 20.2 (IQR=17.1-23.3). When compared to 5174 contemporaneous samples sequenced in our laboratory, VOC were significantly enriched among breakthrough infections (p < .05).

Using model-inference estimates from March 2020 to May 2021, we estimate the Delta variant can escape adaptive immunity induced by prior wildtype infection roughly half of the time and is around 60% more infectious than wildtype SARS-CoV-2. In addition, our analysis suggests that the recent case decline in India was likely due to implemented non-pharmaceutical interventions and weather conditions less conducive for SARS-CoV-2 transmission during March - May, rather than high population immunity.

Sequencing SARS-CoV-2 from wastewater has become a useful tool in monitoring the spread of variants. We use a novel computation workflow with SARS-CoV-2 amplicon sequencing in order to track wastewater populations of the virus. As part of this workflow, we developed a program for both variant reporting and removal of PCR generated chimeric sequences. With these methods, we are able to track viral population dynamics over time. We observe the emergence of the variants of concern B.1.1.7 and P.1, and their displacement of the D614G B.1 variant.

We examined antigen-specific B cell responses in peripheral blood (n=41) and draining lymph nodes (LNs) in 14 individuals who received two doses of BNT162b2, an mRNA-based vaccine encoding full-length SARS-CoV-2 spike (S) gene. We found that SARS-CoV-2 mRNA-based vaccination of humans induces a persistent GC B cell response, enabling the generation of robust humoral immunity.

It is critical to identify putative causal targets for SARS coronavirus 2, which may guide drug repurposing options to reduce the public health burden of COVID-19. We applied complementary methods and multiphased design to pinpoint the most likely causal genes for COVID-19 severity. Through analyses of the COVID-19 HGI using complementary CMO and S-PrediXcan methods along with fine-mapping, XCR1, CCR2, SACM1L, OAS3, NSF, WNT3, NAPSA, and IFNAR2 are identified as putative causal genes for COVID-19 severity.

These data, together with our previous findings, reveal that AZD1222 recipients have lower NAbTs than BNT162b2 recipients against SARS-CoV-2 variants, including B.1.617.2. This finding is in line with the vaccine-induced NAbTs observed during clinical trials of AZD12224 and BNT162b2.

It is important to note that many millions of people have received COVID-19 vaccines that use mRNA technology. This is the only report to date of possible VITT or TTS in those recipients, and such a rare event, even if confirmed by additional reports, should not prevent persons from receiving the benefits of these vaccines.

Using the ARTIC Network amplicon-generation approach with sequencing on the Oxford Nanopore MinION, we demonstrate that sequencing SARS-CoV-2 from saliva produces genomes comparable to those from nasopharyngeal swabs, and that RNA extraction is necessary to generate complete genomes from saliva.

We describe the wide-scale implementation of a reverse transcriptase polymerase chain reaction (RT-PCR) multiple variants assay with melting curve analysis as a routine procedure. We prospectively performed multiple variants RT-PCR on consecutive SARS-CoV-2 RT-PCR positive samples from patients, healthcare workers and nursing home residents from our hospital catchment area. This technique was implemented in our automated Roche FLOW system with a turn-around time of 6 h.

During the study period 55 HCWs were found positive for SARS-CoV-2, most of whom (44/55) were identified from March 28 to April 14 during an in-hospital COVID-19 outbreak. Of the 55 HCWs, 21 were fully vaccinated and another three had received one dose. Most cases (54/55) were due to variant B.1.1.7

Application of the integrated system from August to December 2020 enabled a characterization of viral population structure, analysis of four outbreaks at a maximum care hospital, and genetically based identification of five putative population infection clusters, all of which were confirmed by contact tracing. The system contributed to the development of improved hospital infection control and prevention measures and enabled the identification of previously unrecognized transmission chains, involving a martial arts gym and establishing a link between the hospital to the local population.

In this study of 7 patients with acute myocarditis, 4 occurred within 5 days of COVID-19 vaccination between February 1 and April 30, 2021. All 4 patients had received the second dose of a messenger RNA (mRNA) vaccine, presented with severe chest pain, had biomarker evidence of myocardial injury, were hospitalized, and had cardiac magnetic resonance imaging findings typical of myocarditis.

We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants.

In an analysis of vaccine breakthrough in over 100 healthcare workers across three centres in India, the Delta variant not only dominates vaccine-breakthrough infections with higher respiratory viral loads compared to non-delta infections (Ct value of 16.5 versus 19), but also generates greater transmission between HCW as compared to B.1.1.7 or B.1.617.1 (p=0.02). In vitro, the Delta variant shows 8 fold approximately reduced sensitivity to vaccine-elicited antibodies compared to wild type Wuhan-1 bearing D614G.

Several fast-spreading variants of SARS-CoV-2 have become the dominant circulating strains in the COVID-19 pandemic. We report here cryo-EM structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Amino acid substitutions in the B.1.1.7 protein increase the accessibility of its receptor binding domain and also the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2). The enhanced receptor engagement may account for the increased transmissibility.

Data about APOE expression levels was obtained from the Genotype-Tissue Expression Project and the allele frequencies of APOE variants was acquired from the populations included in the phase 3 release of the 1000 Genomes Project. A total of 128 variants showed a significant impact on the APOE expression in lung tissues (p < 0.0001). Linkage Disequilibrium analysis revealed that 98 variants were closely grouped into seven distinct haplotype blocks, of which six were composed of variants that significantly decrease APOE gene expression in the lungs.

SARS-CoV-2 variants with multiple spike mutations enable increased transmission and antibody resistance. Here, we combine cryo-EM, binding and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans, and others that originated and spread in human populations. All variants showed increased ACE2 receptor binding and increased propensity for RBD up states.

Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOC) and had a median Ct of 20.2 (IQR=17.1-23.3). When compared to 5174 contemporaneous samples sequenced in our laboratory, VOC were significantly enriched among breakthrough infections (p < .05).

Using model-inference estimates from March 2020 to May 2021, we estimate the Delta variant can escape adaptive immunity induced by prior wildtype infection roughly half of the time and is around 60% more infectious than wildtype SARS-CoV-2. In addition, our analysis suggests that the recent case decline in India was likely due to implemented non-pharmaceutical interventions and weather conditions less conducive for SARS-CoV-2 transmission during March - May, rather than high population immunity.

Sequencing SARS-CoV-2 from wastewater has become a useful tool in monitoring the spread of variants. We use a novel computation workflow with SARS-CoV-2 amplicon sequencing in order to track wastewater populations of the virus. As part of this workflow, we developed a program for both variant reporting and removal of PCR generated chimeric sequences. With these methods, we are able to track viral population dynamics over time. We observe the emergence of the variants of concern B.1.1.7 and P.1, and their displacement of the D614G B.1 variant.

We examined antigen-specific B cell responses in peripheral blood (n=41) and draining lymph nodes (LNs) in 14 individuals who received two doses of BNT162b2, an mRNA-based vaccine encoding full-length SARS-CoV-2 spike (S) gene. We found that SARS-CoV-2 mRNA-based vaccination of humans induces a persistent GC B cell response, enabling the generation of robust humoral immunity.

It is critical to identify putative causal targets for SARS coronavirus 2, which may guide drug repurposing options to reduce the public health burden of COVID-19. We applied complementary methods and multiphased design to pinpoint the most likely causal genes for COVID-19 severity. Through analyses of the COVID-19 HGI using complementary CMO and S-PrediXcan methods along with fine-mapping, XCR1, CCR2, SACM1L, OAS3, NSF, WNT3, NAPSA, and IFNAR2 are identified as putative causal genes for COVID-19 severity.

These data, together with our previous findings, reveal that AZD1222 recipients have lower NAbTs than BNT162b2 recipients against SARS-CoV-2 variants, including B.1.617.2. This finding is in line with the vaccine-induced NAbTs observed during clinical trials of AZD12224 and BNT162b2.

It is important to note that many millions of people have received COVID-19 vaccines that use mRNA technology. This is the only report to date of possible VITT or TTS in those recipients, and such a rare event, even if confirmed by additional reports, should not prevent persons from receiving the benefits of these vaccines.

Using the ARTIC Network amplicon-generation approach with sequencing on the Oxford Nanopore MinION, we demonstrate that sequencing SARS-CoV-2 from saliva produces genomes comparable to those from nasopharyngeal swabs, and that RNA extraction is necessary to generate complete genomes from saliva.

We describe the wide-scale implementation of a reverse transcriptase polymerase chain reaction (RT-PCR) multiple variants assay with melting curve analysis as a routine procedure. We prospectively performed multiple variants RT-PCR on consecutive SARS-CoV-2 RT-PCR positive samples from patients, healthcare workers and nursing home residents from our hospital catchment area. This technique was implemented in our automated Roche FLOW system with a turn-around time of 6 h.

During the study period 55 HCWs were found positive for SARS-CoV-2, most of whom (44/55) were identified from March 28 to April 14 during an in-hospital COVID-19 outbreak. Of the 55 HCWs, 21 were fully vaccinated and another three had received one dose. Most cases (54/55) were due to variant B.1.1.7

Application of the integrated system from August to December 2020 enabled a characterization of viral population structure, analysis of four outbreaks at a maximum care hospital, and genetically based identification of five putative population infection clusters, all of which were confirmed by contact tracing. The system contributed to the development of improved hospital infection control and prevention measures and enabled the identification of previously unrecognized transmission chains, involving a martial arts gym and establishing a link between the hospital to the local population.

In this study of 7 patients with acute myocarditis, 4 occurred within 5 days of COVID-19 vaccination between February 1 and April 30, 2021. All 4 patients had received the second dose of a messenger RNA (mRNA) vaccine, presented with severe chest pain, had biomarker evidence of myocardial injury, were hospitalized, and had cardiac magnetic resonance imaging findings typical of myocarditis.

We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants.

In an analysis of vaccine breakthrough in over 100 healthcare workers across three centres in India, the Delta variant not only dominates vaccine-breakthrough infections with higher respiratory viral loads compared to non-delta infections (Ct value of 16.5 versus 19), but also generates greater transmission between HCW as compared to B.1.1.7 or B.1.617.1 (p=0.02). In vitro, the Delta variant shows 8 fold approximately reduced sensitivity to vaccine-elicited antibodies compared to wild type Wuhan-1 bearing D614G.

Several fast-spreading variants of SARS-CoV-2 have become the dominant circulating strains in the COVID-19 pandemic. We report here cryo-EM structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Amino acid substitutions in the B.1.1.7 protein increase the accessibility of its receptor binding domain and also the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2). The enhanced receptor engagement may account for the increased transmissibility.

Data about APOE expression levels was obtained from the Genotype-Tissue Expression Project and the allele frequencies of APOE variants was acquired from the populations included in the phase 3 release of the 1000 Genomes Project. A total of 128 variants showed a significant impact on the APOE expression in lung tissues (p < 0.0001). Linkage Disequilibrium analysis revealed that 98 variants were closely grouped into seven distinct haplotype blocks, of which six were composed of variants that significantly decrease APOE gene expression in the lungs.

SARS-CoV-2 variants with multiple spike mutations enable increased transmission and antibody resistance. Here, we combine cryo-EM, binding and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans, and others that originated and spread in human populations. All variants showed increased ACE2 receptor binding and increased propensity for RBD up states.

Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOC) and had a median Ct of 20.2 (IQR=17.1-23.3). When compared to 5174 contemporaneous samples sequenced in our laboratory, VOC were significantly enriched among breakthrough infections (p < .05).

Using model-inference estimates from March 2020 to May 2021, we estimate the Delta variant can escape adaptive immunity induced by prior wildtype infection roughly half of the time and is around 60% more infectious than wildtype SARS-CoV-2. In addition, our analysis suggests that the recent case decline in India was likely due to implemented non-pharmaceutical interventions and weather conditions less conducive for SARS-CoV-2 transmission during March - May, rather than high population immunity.

Sequencing SARS-CoV-2 from wastewater has become a useful tool in monitoring the spread of variants. We use a novel computation workflow with SARS-CoV-2 amplicon sequencing in order to track wastewater populations of the virus. As part of this workflow, we developed a program for both variant reporting and removal of PCR generated chimeric sequences. With these methods, we are able to track viral population dynamics over time. We observe the emergence of the variants of concern B.1.1.7 and P.1, and their displacement of the D614G B.1 variant.

We examined antigen-specific B cell responses in peripheral blood (n=41) and draining lymph nodes (LNs) in 14 individuals who received two doses of BNT162b2, an mRNA-based vaccine encoding full-length SARS-CoV-2 spike (S) gene. We found that SARS-CoV-2 mRNA-based vaccination of humans induces a persistent GC B cell response, enabling the generation of robust humoral immunity.

It is critical to identify putative causal targets for SARS coronavirus 2, which may guide drug repurposing options to reduce the public health burden of COVID-19. We applied complementary methods and multiphased design to pinpoint the most likely causal genes for COVID-19 severity. Through analyses of the COVID-19 HGI using complementary CMO and S-PrediXcan methods along with fine-mapping, XCR1, CCR2, SACM1L, OAS3, NSF, WNT3, NAPSA, and IFNAR2 are identified as putative causal genes for COVID-19 severity.

These data, together with our previous findings, reveal that AZD1222 recipients have lower NAbTs than BNT162b2 recipients against SARS-CoV-2 variants, including B.1.617.2. This finding is in line with the vaccine-induced NAbTs observed during clinical trials of AZD12224 and BNT162b2.

It is important to note that many millions of people have received COVID-19 vaccines that use mRNA technology. This is the only report to date of possible VITT or TTS in those recipients, and such a rare event, even if confirmed by additional reports, should not prevent persons from receiving the benefits of these vaccines.

Using the ARTIC Network amplicon-generation approach with sequencing on the Oxford Nanopore MinION, we demonstrate that sequencing SARS-CoV-2 from saliva produces genomes comparable to those from nasopharyngeal swabs, and that RNA extraction is necessary to generate complete genomes from saliva.

We describe the wide-scale implementation of a reverse transcriptase polymerase chain reaction (RT-PCR) multiple variants assay with melting curve analysis as a routine procedure. We prospectively performed multiple variants RT-PCR on consecutive SARS-CoV-2 RT-PCR positive samples from patients, healthcare workers and nursing home residents from our hospital catchment area. This technique was implemented in our automated Roche FLOW system with a turn-around time of 6 h.

During the study period 55 HCWs were found positive for SARS-CoV-2, most of whom (44/55) were identified from March 28 to April 14 during an in-hospital COVID-19 outbreak. Of the 55 HCWs, 21 were fully vaccinated and another three had received one dose. Most cases (54/55) were due to variant B.1.1.7

Application of the integrated system from August to December 2020 enabled a characterization of viral population structure, analysis of four outbreaks at a maximum care hospital, and genetically based identification of five putative population infection clusters, all of which were confirmed by contact tracing. The system contributed to the development of improved hospital infection control and prevention measures and enabled the identification of previously unrecognized transmission chains, involving a martial arts gym and establishing a link between the hospital to the local population.

In this study of 7 patients with acute myocarditis, 4 occurred within 5 days of COVID-19 vaccination between February 1 and April 30, 2021. All 4 patients had received the second dose of a messenger RNA (mRNA) vaccine, presented with severe chest pain, had biomarker evidence of myocardial injury, were hospitalized, and had cardiac magnetic resonance imaging findings typical of myocarditis.

We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants.