Published on 01/27/2022
COVID-19 Genomics and Precision Public Health Weekly Update Content
Pathogen and Human Genomics Studies
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A 6-mRNA host response classifier in whole blood predicts outcomes in COVID-19 and other acute viral infections.
Buturovic Ljubomir et al. Scientific reports 2022 1 (1) 889Predicting the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for the severity of viral infections and validate it in independent data, including COVID-19. We developed a logistic regression-based classifier for the severity of viral infections and validated it in multiple viral infection settings including COVID-19. We used training data (N = 705) from 21 retrospective transcriptomic clinical studies of influenza and other viral illnesses looking at a preselected panel of host immune response messenger RNAs. We selected 6 host RNAs and trained logistic regression classifier with a cross-validation area under curve of 0.90 for predicting 30-day mortality in viral illnesses. -
Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose
C Kuhlmann et al, The Lancet, January 18, 2022These were the first documented breakthrough infections with the omicron variant in fully vaccinated individuals after receipt of booster vaccine doses. Some of these individuals had received heterologous vaccine doses, in line with emerging global practice. Booster doses were administered 21–37 weeks after the second vaccine doses, and breakthrough infections occurred 22–59 days thereafter. At the onset of their breakthrough infections, all individuals had high levels of viral spike protein binding antibodies, similar to levels reported 4 weeks following second vaccine doses6 and as expected after receipt of booster vaccine doses. -
Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study
N Wolter et al, The Lancet, January 19, 2022Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity. -
Comparison of mRNA-1273 and BNT162b2 Vaccines on Breakthrough SARS-CoV-2 Infections, Hospitalizations, and Death During the Delta-Predominant Period.
Wang Lindsey et al. JAMA 2022 1This study examined breakthrough infections, hospitalizations, and mortality in a general population for these 2 vaccines during the Delta period while considering risk characteristics of vaccine recipients and the varying time since vaccination.We used the cloud-based TriNetX Analytics Platform to obtain web-based real-time secure access to fully deidentified electronic health records of 89 million patients from 63 health care organizations including inpatient and outpatient settings, representing 27% of the US population from 50 states. The study found that recipients of mRNA-1273 compared with BNT162b2 had a lower risk of breakthrough SARS-CoV-2 infections and hospitalizations during the Delta period. -
Notes from the Field: Early Evidence of the SARS-CoV-2 B.1.1.529 (Omicron) Variant in Community Wastewater - United States, November-December 2021.
Kirby Amy E et al. MMWR. Morbidity and mortality weekly report 2022 1 (3) 103-105The National Wastewater Surveillance System (NWSS) comprises 43 health departments funded by CDC to provide data on presence of and trends in SARS-CoV-2 infections that are independent of clinical testing. In addition to total SARS-CoV-2 testing, some health departments track SARS-CoV-2 variants by detecting variant-associated mutations in wastewater. Health departments in four states (California, Colorado, New York, and Texas) were the first wastewater surveillance programs to detect evidence of Omicron in community wastewater. This report describes the initial detections in wastewater during November 21–December 16, 2021, and the interpretative framework for these types of data. -
Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain.
Nabel Katherine G et al. Science (New York, N.Y.) 2021 12 (6578) eabl6251Throughout the course of the COVID-19 pandemic, variants have arisen in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that increase infectivity or reduce its susceptibility to existing antibodies. a new study focuses on mutations in the spike protein, which is found on the viral surface and is responsible for binding and entering host cells, and show that the structure exhibits plasticity in resisting neutralizing antibodies. -
Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study
SAC Clemens et al, The Lancet, January 21, 2022Antibody concentrations were low at 6 months after previous immunisation with two doses of CoronaVac. However, all four vaccines administered as a third dose induced a significant increase in binding and neutralising antibodies, which could improve protection against infection. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection. -
Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants.
Accorsi Emma K et al. JAMA 2022 1What is the association between 3 doses of mRNA COVID-19 vaccine and symptomatic SARS-CoV-2 infection with the Omicron and Delta variants? In this test-negative case-control analysis that included 70?155 tests from symptomatic adults, the likelihood of vaccination with 3 mRNA vaccine doses (vs unvaccinated) was significantly lower among both Omicron (odds ratio, 0.33) and Delta (odds ratio, 0.065) cases than SARS-CoV-2–negative controls; a similar pattern was observed with 3 vaccine doses vs 2 doses (Omicron odds ratio, 0.34; Delta odds ratio, 0.16). -
Mutations in SARS-CoV-2 variants of concern link to increased spike cleavage and virus transmission
A Escalera et al, Cell Host and Microbe, January 20, 2022SARS-CoV-2 lineages have diverged into highly prevalent variants termed Variants of Concern (VOCs). Here, we characterized emerging SARS-CoV-2 spike polymorphisms in vitro and in vivo to understand their impact on transmissibility, virus pathogenicity and fitness. We demonstrate that the substitution S:655Y, represented in the Gamma and Omicron VOCs, enhances viral replication and spike protein cleavage. -
Trends in Disease Severity and Health Care Utilization During the Early Omicron Variant Period Compared with Previous SARS-CoV-2 High Transmission Periods — United States, December 2020–January 2022
AD Luliano et al, MMWR, January 25, 2022The SARS-CoV-2 B.1.1.529 (Omicron) variant became predominant in the United States by late December 2021, leading to a surge in COVID-19 cases and associated ED visits and hospitalizations. Despite Omicron seeing the highest reported numbers of COVID-19 cases and hospitalizations during the pandemic, disease severity indicators, including length of stay, ICU admission, and death, were lower than during previous pandemic peaks. -
Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021
ME Oster et al, JAMA< January 25, 2022In this descriptive study of 1626 cases of myocarditis in a national passive reporting system, the crude reporting rates within 7 days after vaccination exceeded the expected rates across multiple age and sex strata. The rates of myocarditis cases were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). -
Carditis After COVID-19 Vaccination With a Messenger RNA Vaccine and an Inactivated Virus VaccineFREE
A Case–Control Study
TTT Lai et al, Ann Int Med, January 25, 2022A total of 160 case patients and 1533 control participants were included. Incidence of carditis per 100 000 doses of CoronaVac and BNT162b2 administered was estimated to be 0.31 (95% CI, 0.13 to 0.66) and 0.57 (CI, 0.36 to 0.90), respectively. Multivariable analyses showed that recipients of the BNT162b2 vaccine had higher odds of carditis (adjusted odds ratio [OR], 3.57 [CI, 1.93 to 6.60]) than unvaccinated persons. Stratified by sex, the OR was 4.68 (CI, 2.25 to 9.71) for males and 2.22 (CI, 0.57 to 8.69) for females receiving the BNT162b2 vaccine. The ORs for adults and adolescents receiving the BNT162b2 vaccine were 2.41 (CI, 1.18 to 4.90) and 13.79 (CI, 2.86 to 110.38), respectively. -
Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant.
Li Baisheng et al. Nature communications 2022 1 (1) 460We report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. -
Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar.
Chemaitelly Hiam et al. The New England journal of medicine 2021 10 (24) e83 -
Homologous and Heterologous Covid-19 Booster Vaccinations.
Atmar Robert L et al. The New England journal of medicine 2022 1In this phase 1–2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 µg, Ad26.COV2.S (Johnson & Johnson–Janssen) at a dose of 5×1010 virus particles, or BNT162b2 (Pfizer–BioNTech) at a dose of 30 µg. We found that homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier -
Myocarditis after BNT162b2 Vaccination in Israeli Adolescents.
Mevorach Dror et al. The New England journal of medicine 2022 1The risk estimates of myocarditis among male recipients in the 21 days after the first and second doses were 0.56 cases per 100,000 after the first dose and 8.09 cases per 100,000 after the second dose; the risk estimates among female recipients were 0 cases per 100,000 after the first dose and 0.69 cases per 100,000 after the second dose. The risk of myocarditis after receipt of the second vaccine dose among male adolescents 12 to 15 years of age was estimated to be 1 case per 12,361; the corresponding risk among female adolescents was estimated to be 1 case per 144,439. -
SARS-CoV-2 Omicron Variant Neutralization after mRNA-1273 Booster Vaccination.
Pajon Rolando et al. The New England journal of medicine 2022 1We show that after the primary two-dose series of the mRNA-1273 vaccine, neutralization titers against the omicron variant were 35.0 times lower than those against the D614G variant. These lower titers could lead to an increased risk of severe breakthrough infection. However, a booster dose of mRNA-1273 vaccine was associated with neutralization titers against the omicron variant that were 20.0 times higher than those assessed after the second dose of vaccine, and these titers may substantially reduce the risk of breakthrough infection. The decline in neutralization of the omicron variant 6 months after the booster injection was similar to the decline in neutralization titers against the D614G variant 7 months after the second dose.
Non-Genomics Precision Health Studies
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A 6-mRNA host response classifier in whole blood predicts outcomes in COVID-19 and other acute viral infections.
Buturovic Ljubomir et al. Scientific reports 2022 1 (1) 889Predicting the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for the severity of viral infections and validate it in independent data, including COVID-19. We developed a logistic regression-based classifier for the severity of viral infections and validated it in multiple viral infection settings including COVID-19. We used training data (N = 705) from 21 retrospective transcriptomic clinical studies of influenza and other viral illnesses looking at a preselected panel of host immune response messenger RNAs. We selected 6 host RNAs and trained logistic regression classifier with a cross-validation area under curve of 0.90 for predicting 30-day mortality in viral illnesses. -
Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose
C Kuhlmann et al, The Lancet, January 18, 2022These were the first documented breakthrough infections with the omicron variant in fully vaccinated individuals after receipt of booster vaccine doses. Some of these individuals had received heterologous vaccine doses, in line with emerging global practice. Booster doses were administered 21–37 weeks after the second vaccine doses, and breakthrough infections occurred 22–59 days thereafter. At the onset of their breakthrough infections, all individuals had high levels of viral spike protein binding antibodies, similar to levels reported 4 weeks following second vaccine doses6 and as expected after receipt of booster vaccine doses. -
Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study
N Wolter et al, The Lancet, January 19, 2022Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity. -
Comparison of mRNA-1273 and BNT162b2 Vaccines on Breakthrough SARS-CoV-2 Infections, Hospitalizations, and Death During the Delta-Predominant Period.
Wang Lindsey et al. JAMA 2022 1This study examined breakthrough infections, hospitalizations, and mortality in a general population for these 2 vaccines during the Delta period while considering risk characteristics of vaccine recipients and the varying time since vaccination.We used the cloud-based TriNetX Analytics Platform to obtain web-based real-time secure access to fully deidentified electronic health records of 89 million patients from 63 health care organizations including inpatient and outpatient settings, representing 27% of the US population from 50 states. The study found that recipients of mRNA-1273 compared with BNT162b2 had a lower risk of breakthrough SARS-CoV-2 infections and hospitalizations during the Delta period. -
Notes from the Field: Early Evidence of the SARS-CoV-2 B.1.1.529 (Omicron) Variant in Community Wastewater - United States, November-December 2021.
Kirby Amy E et al. MMWR. Morbidity and mortality weekly report 2022 1 (3) 103-105The National Wastewater Surveillance System (NWSS) comprises 43 health departments funded by CDC to provide data on presence of and trends in SARS-CoV-2 infections that are independent of clinical testing. In addition to total SARS-CoV-2 testing, some health departments track SARS-CoV-2 variants by detecting variant-associated mutations in wastewater. Health departments in four states (California, Colorado, New York, and Texas) were the first wastewater surveillance programs to detect evidence of Omicron in community wastewater. This report describes the initial detections in wastewater during November 21–December 16, 2021, and the interpretative framework for these types of data. -
Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain.
Nabel Katherine G et al. Science (New York, N.Y.) 2021 12 (6578) eabl6251Throughout the course of the COVID-19 pandemic, variants have arisen in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that increase infectivity or reduce its susceptibility to existing antibodies. a new study focuses on mutations in the spike protein, which is found on the viral surface and is responsible for binding and entering host cells, and show that the structure exhibits plasticity in resisting neutralizing antibodies. -
Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study
SAC Clemens et al, The Lancet, January 21, 2022Antibody concentrations were low at 6 months after previous immunisation with two doses of CoronaVac. However, all four vaccines administered as a third dose induced a significant increase in binding and neutralising antibodies, which could improve protection against infection. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection. -
Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants.
Accorsi Emma K et al. JAMA 2022 1What is the association between 3 doses of mRNA COVID-19 vaccine and symptomatic SARS-CoV-2 infection with the Omicron and Delta variants? In this test-negative case-control analysis that included 70?155 tests from symptomatic adults, the likelihood of vaccination with 3 mRNA vaccine doses (vs unvaccinated) was significantly lower among both Omicron (odds ratio, 0.33) and Delta (odds ratio, 0.065) cases than SARS-CoV-2–negative controls; a similar pattern was observed with 3 vaccine doses vs 2 doses (Omicron odds ratio, 0.34; Delta odds ratio, 0.16). -
Mutations in SARS-CoV-2 variants of concern link to increased spike cleavage and virus transmission
A Escalera et al, Cell Host and Microbe, January 20, 2022SARS-CoV-2 lineages have diverged into highly prevalent variants termed Variants of Concern (VOCs). Here, we characterized emerging SARS-CoV-2 spike polymorphisms in vitro and in vivo to understand their impact on transmissibility, virus pathogenicity and fitness. We demonstrate that the substitution S:655Y, represented in the Gamma and Omicron VOCs, enhances viral replication and spike protein cleavage. -
Trends in Disease Severity and Health Care Utilization During the Early Omicron Variant Period Compared with Previous SARS-CoV-2 High Transmission Periods — United States, December 2020–January 2022
AD Luliano et al, MMWR, January 25, 2022The SARS-CoV-2 B.1.1.529 (Omicron) variant became predominant in the United States by late December 2021, leading to a surge in COVID-19 cases and associated ED visits and hospitalizations. Despite Omicron seeing the highest reported numbers of COVID-19 cases and hospitalizations during the pandemic, disease severity indicators, including length of stay, ICU admission, and death, were lower than during previous pandemic peaks. -
Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021
ME Oster et al, JAMA< January 25, 2022In this descriptive study of 1626 cases of myocarditis in a national passive reporting system, the crude reporting rates within 7 days after vaccination exceeded the expected rates across multiple age and sex strata. The rates of myocarditis cases were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). -
Carditis After COVID-19 Vaccination With a Messenger RNA Vaccine and an Inactivated Virus VaccineFREE
A Case–Control Study
TTT Lai et al, Ann Int Med, January 25, 2022A total of 160 case patients and 1533 control participants were included. Incidence of carditis per 100 000 doses of CoronaVac and BNT162b2 administered was estimated to be 0.31 (95% CI, 0.13 to 0.66) and 0.57 (CI, 0.36 to 0.90), respectively. Multivariable analyses showed that recipients of the BNT162b2 vaccine had higher odds of carditis (adjusted odds ratio [OR], 3.57 [CI, 1.93 to 6.60]) than unvaccinated persons. Stratified by sex, the OR was 4.68 (CI, 2.25 to 9.71) for males and 2.22 (CI, 0.57 to 8.69) for females receiving the BNT162b2 vaccine. The ORs for adults and adolescents receiving the BNT162b2 vaccine were 2.41 (CI, 1.18 to 4.90) and 13.79 (CI, 2.86 to 110.38), respectively. -
Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant.
Li Baisheng et al. Nature communications 2022 1 (1) 460We report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. -
Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar.
Chemaitelly Hiam et al. The New England journal of medicine 2021 10 (24) e83 -
Homologous and Heterologous Covid-19 Booster Vaccinations.
Atmar Robert L et al. The New England journal of medicine 2022 1In this phase 1–2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 µg, Ad26.COV2.S (Johnson & Johnson–Janssen) at a dose of 5×1010 virus particles, or BNT162b2 (Pfizer–BioNTech) at a dose of 30 µg. We found that homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier -
Myocarditis after BNT162b2 Vaccination in Israeli Adolescents.
Mevorach Dror et al. The New England journal of medicine 2022 1The risk estimates of myocarditis among male recipients in the 21 days after the first and second doses were 0.56 cases per 100,000 after the first dose and 8.09 cases per 100,000 after the second dose; the risk estimates among female recipients were 0 cases per 100,000 after the first dose and 0.69 cases per 100,000 after the second dose. The risk of myocarditis after receipt of the second vaccine dose among male adolescents 12 to 15 years of age was estimated to be 1 case per 12,361; the corresponding risk among female adolescents was estimated to be 1 case per 144,439. -
SARS-CoV-2 Omicron Variant Neutralization after mRNA-1273 Booster Vaccination.
Pajon Rolando et al. The New England journal of medicine 2022 1We show that after the primary two-dose series of the mRNA-1273 vaccine, neutralization titers against the omicron variant were 35.0 times lower than those against the D614G variant. These lower titers could lead to an increased risk of severe breakthrough infection. However, a booster dose of mRNA-1273 vaccine was associated with neutralization titers against the omicron variant that were 20.0 times higher than those assessed after the second dose of vaccine, and these titers may substantially reduce the risk of breakthrough infection. The decline in neutralization of the omicron variant 6 months after the booster injection was similar to the decline in neutralization titers against the D614G variant 7 months after the second dose.
News, Reviews and Commentaries
-
A 6-mRNA host response classifier in whole blood predicts outcomes in COVID-19 and other acute viral infections.
Buturovic Ljubomir et al. Scientific reports 2022 1 (1) 889Predicting the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for the severity of viral infections and validate it in independent data, including COVID-19. We developed a logistic regression-based classifier for the severity of viral infections and validated it in multiple viral infection settings including COVID-19. We used training data (N = 705) from 21 retrospective transcriptomic clinical studies of influenza and other viral illnesses looking at a preselected panel of host immune response messenger RNAs. We selected 6 host RNAs and trained logistic regression classifier with a cross-validation area under curve of 0.90 for predicting 30-day mortality in viral illnesses. -
Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose
C Kuhlmann et al, The Lancet, January 18, 2022These were the first documented breakthrough infections with the omicron variant in fully vaccinated individuals after receipt of booster vaccine doses. Some of these individuals had received heterologous vaccine doses, in line with emerging global practice. Booster doses were administered 21–37 weeks after the second vaccine doses, and breakthrough infections occurred 22–59 days thereafter. At the onset of their breakthrough infections, all individuals had high levels of viral spike protein binding antibodies, similar to levels reported 4 weeks following second vaccine doses6 and as expected after receipt of booster vaccine doses. -
Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study
N Wolter et al, The Lancet, January 19, 2022Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity. -
Comparison of mRNA-1273 and BNT162b2 Vaccines on Breakthrough SARS-CoV-2 Infections, Hospitalizations, and Death During the Delta-Predominant Period.
Wang Lindsey et al. JAMA 2022 1This study examined breakthrough infections, hospitalizations, and mortality in a general population for these 2 vaccines during the Delta period while considering risk characteristics of vaccine recipients and the varying time since vaccination.We used the cloud-based TriNetX Analytics Platform to obtain web-based real-time secure access to fully deidentified electronic health records of 89 million patients from 63 health care organizations including inpatient and outpatient settings, representing 27% of the US population from 50 states. The study found that recipients of mRNA-1273 compared with BNT162b2 had a lower risk of breakthrough SARS-CoV-2 infections and hospitalizations during the Delta period. -
Notes from the Field: Early Evidence of the SARS-CoV-2 B.1.1.529 (Omicron) Variant in Community Wastewater - United States, November-December 2021.
Kirby Amy E et al. MMWR. Morbidity and mortality weekly report 2022 1 (3) 103-105The National Wastewater Surveillance System (NWSS) comprises 43 health departments funded by CDC to provide data on presence of and trends in SARS-CoV-2 infections that are independent of clinical testing. In addition to total SARS-CoV-2 testing, some health departments track SARS-CoV-2 variants by detecting variant-associated mutations in wastewater. Health departments in four states (California, Colorado, New York, and Texas) were the first wastewater surveillance programs to detect evidence of Omicron in community wastewater. This report describes the initial detections in wastewater during November 21–December 16, 2021, and the interpretative framework for these types of data. -
Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain.
Nabel Katherine G et al. Science (New York, N.Y.) 2021 12 (6578) eabl6251Throughout the course of the COVID-19 pandemic, variants have arisen in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that increase infectivity or reduce its susceptibility to existing antibodies. a new study focuses on mutations in the spike protein, which is found on the viral surface and is responsible for binding and entering host cells, and show that the structure exhibits plasticity in resisting neutralizing antibodies. -
Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study
SAC Clemens et al, The Lancet, January 21, 2022Antibody concentrations were low at 6 months after previous immunisation with two doses of CoronaVac. However, all four vaccines administered as a third dose induced a significant increase in binding and neutralising antibodies, which could improve protection against infection. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection. -
Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants.
Accorsi Emma K et al. JAMA 2022 1What is the association between 3 doses of mRNA COVID-19 vaccine and symptomatic SARS-CoV-2 infection with the Omicron and Delta variants? In this test-negative case-control analysis that included 70?155 tests from symptomatic adults, the likelihood of vaccination with 3 mRNA vaccine doses (vs unvaccinated) was significantly lower among both Omicron (odds ratio, 0.33) and Delta (odds ratio, 0.065) cases than SARS-CoV-2–negative controls; a similar pattern was observed with 3 vaccine doses vs 2 doses (Omicron odds ratio, 0.34; Delta odds ratio, 0.16). -
Mutations in SARS-CoV-2 variants of concern link to increased spike cleavage and virus transmission
A Escalera et al, Cell Host and Microbe, January 20, 2022SARS-CoV-2 lineages have diverged into highly prevalent variants termed Variants of Concern (VOCs). Here, we characterized emerging SARS-CoV-2 spike polymorphisms in vitro and in vivo to understand their impact on transmissibility, virus pathogenicity and fitness. We demonstrate that the substitution S:655Y, represented in the Gamma and Omicron VOCs, enhances viral replication and spike protein cleavage. -
Trends in Disease Severity and Health Care Utilization During the Early Omicron Variant Period Compared with Previous SARS-CoV-2 High Transmission Periods — United States, December 2020–January 2022
AD Luliano et al, MMWR, January 25, 2022The SARS-CoV-2 B.1.1.529 (Omicron) variant became predominant in the United States by late December 2021, leading to a surge in COVID-19 cases and associated ED visits and hospitalizations. Despite Omicron seeing the highest reported numbers of COVID-19 cases and hospitalizations during the pandemic, disease severity indicators, including length of stay, ICU admission, and death, were lower than during previous pandemic peaks. -
Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021
ME Oster et al, JAMA< January 25, 2022In this descriptive study of 1626 cases of myocarditis in a national passive reporting system, the crude reporting rates within 7 days after vaccination exceeded the expected rates across multiple age and sex strata. The rates of myocarditis cases were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). -
Carditis After COVID-19 Vaccination With a Messenger RNA Vaccine and an Inactivated Virus VaccineFREE
A Case–Control Study
TTT Lai et al, Ann Int Med, January 25, 2022A total of 160 case patients and 1533 control participants were included. Incidence of carditis per 100 000 doses of CoronaVac and BNT162b2 administered was estimated to be 0.31 (95% CI, 0.13 to 0.66) and 0.57 (CI, 0.36 to 0.90), respectively. Multivariable analyses showed that recipients of the BNT162b2 vaccine had higher odds of carditis (adjusted odds ratio [OR], 3.57 [CI, 1.93 to 6.60]) than unvaccinated persons. Stratified by sex, the OR was 4.68 (CI, 2.25 to 9.71) for males and 2.22 (CI, 0.57 to 8.69) for females receiving the BNT162b2 vaccine. The ORs for adults and adolescents receiving the BNT162b2 vaccine were 2.41 (CI, 1.18 to 4.90) and 13.79 (CI, 2.86 to 110.38), respectively. -
Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant.
Li Baisheng et al. Nature communications 2022 1 (1) 460We report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. -
Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar.
Chemaitelly Hiam et al. The New England journal of medicine 2021 10 (24) e83 -
Homologous and Heterologous Covid-19 Booster Vaccinations.
Atmar Robert L et al. The New England journal of medicine 2022 1In this phase 1–2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 µg, Ad26.COV2.S (Johnson & Johnson–Janssen) at a dose of 5×1010 virus particles, or BNT162b2 (Pfizer–BioNTech) at a dose of 30 µg. We found that homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier -
Myocarditis after BNT162b2 Vaccination in Israeli Adolescents.
Mevorach Dror et al. The New England journal of medicine 2022 1The risk estimates of myocarditis among male recipients in the 21 days after the first and second doses were 0.56 cases per 100,000 after the first dose and 8.09 cases per 100,000 after the second dose; the risk estimates among female recipients were 0 cases per 100,000 after the first dose and 0.69 cases per 100,000 after the second dose. The risk of myocarditis after receipt of the second vaccine dose among male adolescents 12 to 15 years of age was estimated to be 1 case per 12,361; the corresponding risk among female adolescents was estimated to be 1 case per 144,439. -
SARS-CoV-2 Omicron Variant Neutralization after mRNA-1273 Booster Vaccination.
Pajon Rolando et al. The New England journal of medicine 2022 1We show that after the primary two-dose series of the mRNA-1273 vaccine, neutralization titers against the omicron variant were 35.0 times lower than those against the D614G variant. These lower titers could lead to an increased risk of severe breakthrough infection. However, a booster dose of mRNA-1273 vaccine was associated with neutralization titers against the omicron variant that were 20.0 times higher than those assessed after the second dose of vaccine, and these titers may substantially reduce the risk of breakthrough infection. The decline in neutralization of the omicron variant 6 months after the booster injection was similar to the decline in neutralization titers against the D614G variant 7 months after the second dose.
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