This study demonstrates that the COVID-19 pandemic shutdown led to delayed endoscopic surveillance in Lynch syndrome, with potentially impactful delays among young patients. This data also emphasizes the importance of timely surveillance in Lynch syndrome during this current, as well as potential future, global pandemics.

We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal (Mycoplasma salivarium), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality.

To survey for these novel variants in our patient population in New York City, PCR assays were designed to identify viruses with two signature mutations, E484K and N501Y. We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.3% in the past two weeks.

To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation, hospitalization and susceptibility.

We hypothesize that, in addition to viral load and host antibody repertoire, host genetic variants influence vulnerability to infection. Here we apply human induced pluripotent stem cell (hiPSC)-based models and CRISPR engineering to explore the host genetics of SARS-CoV-2. We demonstrate that a single-nucleotide polymorphism (rs4702), common in the population and located in the 3' UTR of the protease FURIN, influences alveolar and neuron infection by SARS-CoV-2 in vitro.

Here, using a live virus neutralization assay (LVNA), we compared neutral- ization of a first wave virus (B.1.1.117) versus the 501Y.V2 variant using plasma collected from adults hospitalized with COVID-19 from two South African infection waves, with the second wave dominated by 501Y.V2 infections.

In this matched cohort study of 54,773 pairs of participants matched by age, gender, ethnicity, index of multiple deprivation, lower tier local authority region, and sample date of positive specimen, and differing only by detectability of the spike protein gene. Death within 28 days after first positive test was higher among patients with VOC-202012/01. (hazard ratio 1.7, 95% CI 1.3-2.2).

The Wadsworth Center sought to characterize the transmission dynamics of SARS-CoV-2 across the entire state of New York from March to September with the addition of over 600 genomes from under-sampled and previously unsampled New York counties and to more fully understand the breadth of the initial outbreak in Westchester County. Additional sequencing confirmed the dominance of B.1 and descendant lineages (collectively referred to as B.1.X) in New York State.

Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers on patients with COVID-19 and DS. Data collected between April and October 2020 (N=1046) were analyzed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS.

We conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P = 4.94 x 10-8) near the natriuretic peptide receptor 3 gene (NPR3). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission.

"In RNA virus evolution, stochastic processes like narrow transmission bottlenecks and genetic drift typically act to constrain the overall pace of adaptive evolution. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge. This underscores the importance of continued genomic surveillance for new SARS-CoV-2 variants as well as heightened scrutiny for signatures of SARS-CoV-2 positive selection in humans and mammalian model systems."

"Houston is the first city in the United States to have all variants documented by genome sequencing. As vaccine deployment accelerates worldwide, increased genomic surveillance of SARS-CoV-2 is essential to understanding the presence and frequency of consequential variants and their patterns and trajectory of dissemination."

"Seropositivity across these seven homes [with no reported COVID cases) varied between 10.7-56.5%, with four exceeding community seroprevalence in London (14.8%). Seropositivity rates for staff and residents correlated significantly (rs 0.84, [95% CI 0.51-0.95] p <0.001) across the 13 homes. WGS identified multiple introductions into some homes and silent transmission of a single lineage between staff and residents in one home.

Using statistical and dynamic modelling approaches, we estimate that this variant has a 43–90%, higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and an accelerated vaccine roll-out, COVID-19 hospitalizations and deaths across England in 2021 will exceed those in 2020.

We have observed delayed large local reactions to the mRNA-1273 vaccine, with a median onset on day 8 (range, 4 to 11) after the first dose. These reactions had a variable appearance. Here, we report on a series of 12 patients with these reactions, all of which appeared near the injection site after complete resolution of the initial local and systemic symptoms associated with vaccination.

This study demonstrates that the COVID-19 pandemic shutdown led to delayed endoscopic surveillance in Lynch syndrome, with potentially impactful delays among young patients. This data also emphasizes the importance of timely surveillance in Lynch syndrome during this current, as well as potential future, global pandemics.

We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal (Mycoplasma salivarium), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality.

To survey for these novel variants in our patient population in New York City, PCR assays were designed to identify viruses with two signature mutations, E484K and N501Y. We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.3% in the past two weeks.

To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation, hospitalization and susceptibility.

We hypothesize that, in addition to viral load and host antibody repertoire, host genetic variants influence vulnerability to infection. Here we apply human induced pluripotent stem cell (hiPSC)-based models and CRISPR engineering to explore the host genetics of SARS-CoV-2. We demonstrate that a single-nucleotide polymorphism (rs4702), common in the population and located in the 3' UTR of the protease FURIN, influences alveolar and neuron infection by SARS-CoV-2 in vitro.

Here, using a live virus neutralization assay (LVNA), we compared neutral- ization of a first wave virus (B.1.1.117) versus the 501Y.V2 variant using plasma collected from adults hospitalized with COVID-19 from two South African infection waves, with the second wave dominated by 501Y.V2 infections.

In this matched cohort study of 54,773 pairs of participants matched by age, gender, ethnicity, index of multiple deprivation, lower tier local authority region, and sample date of positive specimen, and differing only by detectability of the spike protein gene. Death within 28 days after first positive test was higher among patients with VOC-202012/01. (hazard ratio 1.7, 95% CI 1.3-2.2).

The Wadsworth Center sought to characterize the transmission dynamics of SARS-CoV-2 across the entire state of New York from March to September with the addition of over 600 genomes from under-sampled and previously unsampled New York counties and to more fully understand the breadth of the initial outbreak in Westchester County. Additional sequencing confirmed the dominance of B.1 and descendant lineages (collectively referred to as B.1.X) in New York State.

Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers on patients with COVID-19 and DS. Data collected between April and October 2020 (N=1046) were analyzed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS.

We conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P = 4.94 x 10-8) near the natriuretic peptide receptor 3 gene (NPR3). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission.

"In RNA virus evolution, stochastic processes like narrow transmission bottlenecks and genetic drift typically act to constrain the overall pace of adaptive evolution. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge. This underscores the importance of continued genomic surveillance for new SARS-CoV-2 variants as well as heightened scrutiny for signatures of SARS-CoV-2 positive selection in humans and mammalian model systems."

"Houston is the first city in the United States to have all variants documented by genome sequencing. As vaccine deployment accelerates worldwide, increased genomic surveillance of SARS-CoV-2 is essential to understanding the presence and frequency of consequential variants and their patterns and trajectory of dissemination."

"Seropositivity across these seven homes [with no reported COVID cases) varied between 10.7-56.5%, with four exceeding community seroprevalence in London (14.8%). Seropositivity rates for staff and residents correlated significantly (rs 0.84, [95% CI 0.51-0.95] p <0.001) across the 13 homes. WGS identified multiple introductions into some homes and silent transmission of a single lineage between staff and residents in one home.

Using statistical and dynamic modelling approaches, we estimate that this variant has a 43–90%, higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and an accelerated vaccine roll-out, COVID-19 hospitalizations and deaths across England in 2021 will exceed those in 2020.

We have observed delayed large local reactions to the mRNA-1273 vaccine, with a median onset on day 8 (range, 4 to 11) after the first dose. These reactions had a variable appearance. Here, we report on a series of 12 patients with these reactions, all of which appeared near the injection site after complete resolution of the initial local and systemic symptoms associated with vaccination.

This study demonstrates that the COVID-19 pandemic shutdown led to delayed endoscopic surveillance in Lynch syndrome, with potentially impactful delays among young patients. This data also emphasizes the importance of timely surveillance in Lynch syndrome during this current, as well as potential future, global pandemics.

We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal (Mycoplasma salivarium), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality.

To survey for these novel variants in our patient population in New York City, PCR assays were designed to identify viruses with two signature mutations, E484K and N501Y. We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.3% in the past two weeks.

To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation, hospitalization and susceptibility.

We hypothesize that, in addition to viral load and host antibody repertoire, host genetic variants influence vulnerability to infection. Here we apply human induced pluripotent stem cell (hiPSC)-based models and CRISPR engineering to explore the host genetics of SARS-CoV-2. We demonstrate that a single-nucleotide polymorphism (rs4702), common in the population and located in the 3' UTR of the protease FURIN, influences alveolar and neuron infection by SARS-CoV-2 in vitro.

Here, using a live virus neutralization assay (LVNA), we compared neutral- ization of a first wave virus (B.1.1.117) versus the 501Y.V2 variant using plasma collected from adults hospitalized with COVID-19 from two South African infection waves, with the second wave dominated by 501Y.V2 infections.

In this matched cohort study of 54,773 pairs of participants matched by age, gender, ethnicity, index of multiple deprivation, lower tier local authority region, and sample date of positive specimen, and differing only by detectability of the spike protein gene. Death within 28 days after first positive test was higher among patients with VOC-202012/01. (hazard ratio 1.7, 95% CI 1.3-2.2).

The Wadsworth Center sought to characterize the transmission dynamics of SARS-CoV-2 across the entire state of New York from March to September with the addition of over 600 genomes from under-sampled and previously unsampled New York counties and to more fully understand the breadth of the initial outbreak in Westchester County. Additional sequencing confirmed the dominance of B.1 and descendant lineages (collectively referred to as B.1.X) in New York State.

Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers on patients with COVID-19 and DS. Data collected between April and October 2020 (N=1046) were analyzed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS.

We conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P = 4.94 x 10-8) near the natriuretic peptide receptor 3 gene (NPR3). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission.

"In RNA virus evolution, stochastic processes like narrow transmission bottlenecks and genetic drift typically act to constrain the overall pace of adaptive evolution. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge. This underscores the importance of continued genomic surveillance for new SARS-CoV-2 variants as well as heightened scrutiny for signatures of SARS-CoV-2 positive selection in humans and mammalian model systems."

"Houston is the first city in the United States to have all variants documented by genome sequencing. As vaccine deployment accelerates worldwide, increased genomic surveillance of SARS-CoV-2 is essential to understanding the presence and frequency of consequential variants and their patterns and trajectory of dissemination."

"Seropositivity across these seven homes [with no reported COVID cases) varied between 10.7-56.5%, with four exceeding community seroprevalence in London (14.8%). Seropositivity rates for staff and residents correlated significantly (rs 0.84, [95% CI 0.51-0.95] p <0.001) across the 13 homes. WGS identified multiple introductions into some homes and silent transmission of a single lineage between staff and residents in one home.

Using statistical and dynamic modelling approaches, we estimate that this variant has a 43–90%, higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and an accelerated vaccine roll-out, COVID-19 hospitalizations and deaths across England in 2021 will exceed those in 2020.

We have observed delayed large local reactions to the mRNA-1273 vaccine, with a median onset on day 8 (range, 4 to 11) after the first dose. These reactions had a variable appearance. Here, we report on a series of 12 patients with these reactions, all of which appeared near the injection site after complete resolution of the initial local and systemic symptoms associated with vaccination.