Pathogen and Human Genomics Studies
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months
SJ Thomas et al, NEJM, September 15, 2021>
Vaccine efficacy against Covid-19 was 91.3% (95% confidence interval [CI], 89.0 to 93.2) through 6 months of follow-up among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated. There was a gradual decline in vaccine efficacy. Vaccine efficacy of 86 to 100% was seen across countries and in populations with diverse ages, sexes, race or ethnic groups, and risk factors for Covid-19 among participants without evidence of previous infection with SARS-CoV-2. Vaccine efficacy against severe disease was 96.7% (95% CI, 80.3 to 99.9). In South Africa, where the SARS-CoV-2 variant of concern B.1.351 (or beta) was predominant, a vaccine efficacy of 100% (95% CI, 53.5 to 100) was observed.
Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel
YM Bar-On et al, NEJM, September 15, 2021>
In this study involving participants who were 60 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, we found that the rates of confirmed Covid-19 and severe illness were substantially lower among those who received a booster (third) dose of the BNT162b2 vaccine.
Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis
A Choi et al, Nature Medicine, September 15, 2021>
Clinical trial participants who received a two-dose primary series of the COVID-19 vaccine mRNA-1273 approximately 6 months earlier entered an open-label phase 2a study (NCT04405076) to evaluate the primary objectives of safety and immunogenicity of a single booster dose of mRNA-1273 or variant-modified mRNAs, including multivalent mRNA-1273.211. As the trial is currently ongoing, this exploratory interim analysis includes preliminary descriptive results only of four booster groups (n?=?20 per group). Immediately before the booster dose, neutralizing antibodies against wild-type D614G virus had waned (P?<?0.0001) relative to peak titers against wild-type D614G measured 1 month after the primary series, and neutralization titers against B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta) VOCs were either low or undetectable. Both the mRNA-1273 booster and variant-modified boosters were safe and well-tolerated.
Analysis of 2.1 million SARS-CoV-2 genomes identifies mutations associated with transmissibility
FH Obermeyer et al, MEDRXIV, September 13, 2021>
We developed PyR0, a hierarchical Bayesian multinomial logistic regression model that infers relative transmissibility of all viral lineages across geographic regions, detects lineages increasing in prevalence, and identifies mutations relevant to transmissibility. Applying PyR0 to all publicly available SARS-CoV-2 genomes, we identify numerous substitutions that increase transmissibility, including previously identified spike mutations and many non-spike mutations within the nucleocapsid and nonstructural proteins.
Considerations in boosting COVID-19 vaccine immune responses
PR Krause et al, Lancet, September 13, 2021>
Although the idea of further reducing the number of COVID-19 cases by enhancing immunity in vaccinated people is appealing, any decision to do so should be evidence-based and consider the benefits and risks for individuals and society. COVID-19 vaccines continue to be effective against severe disease, including that caused by the delta variant.
Emergence of an early SARS-CoV-2 epidemic in the United States.
Zeller Mark et al. Cell 2021 9 >
To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large-scale events accelerate transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana had limited diversity compared to other U.S. states and that one introduction of SARS-CoV-2 led to almost all of the early transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras, and the festival dramatically accelerated transmission.
A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa
E Wilkinson et al, Science, September 10, 2021>
Progression of the SARS-CoV-2 pandemic in Africa has so far been heterogeneous and the full impact is not yet well understood. Here, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest.
Causal Associations Between Blood Lipids and COVID-19 Risk: A Two-Sample Mendelian Randomization Study.
Zhang Kun et al. Arteriosclerosis, thrombosis, and vascular biology 2021 9 ATVBAHA121316324>
We performed 2-sample Mendelian randomization (MR) analyses to explore the causal effects of blood lipids on COVID-19 susceptibility and severity. Using the outcome data from the UK Biobank (1221 cases and 4117 controls), we observed potential positive causal effects of dyslipidemia (odds ratio [OR], 1.27 [95% CI, 1.08-1.49], P=3.18×10-3), total cholesterol (OR, 1.19 [95% CI, 1.07-1.32], P=8.54×10-4), and ApoB (apolipoprotein B; OR, 1.18 [95% CI, 1.07-1.29], P=1.01×10-3) on COVID-19 susceptibility.
Genomics, social media and mobile phone data enable mapping of SARS-CoV-2 lineages to inform health policy in Bangladesh.
Cowley Lauren A et al. Nature microbiology 2021 9 >
We sequenced the complete genomes of 67 SARS-CoV-2 samples (collected by the IEDCR in Bangladesh between March and July 2020) and combined these data with 324 publicly available Global Initiative on Sharing All Influenza Data (GISAID) SARS-CoV-2 genomes from Bangladesh at that time. We found that most (85%) of the sequenced isolates were Pango lineage B.1.1.25 (58%), B.1.1 (19%) or B.1.36 (8%) in early-mid 2020. Bayesian time-scaled phylogenetic analysis predicted that SARS-CoV-2 first emerged during mid-February in Bangladesh, from abroad, with the first case of coronavirus disease 2019 (COVID-19) reported on 8 March 2020. At the end of March 2020, three discrete lineages expanded and spread clonally across Bangladesh. The shifting pattern of viral diversity in Bangladesh, combined with the mobility data, revealed that the mass migration of people from cities to rural areas at the end of March, followed by frequent travel between Dhaka (the capital of Bangladesh) and the rest of the country, disseminated three dominant viral lineages.
Unexpected details regarding nosocomial transmission revealed by whole-genome sequencing of severe acute respiratory coronavirus virus 2 (SARS-CoV-2).
Myhrman Sofia et al. Infection control and hospital epidemiology 2021 9 1-5>
Effective infection prevention and control (IPC) measures are key for protecting patients from nosocomial infections and require knowledge of transmission mechanisms in different settings. We performed a detailed outbreak analysis of the transmission and outcome of coronavirus disease 2019 (COVID-19) in a geriatric ward by combining whole-genome sequencing (WGS) with epidemiological data.
Using Wastewater Surveillance Data to Support the COVID-19 Response - United States, 2020-2021.
Kirby Amy E et al. MMWR. Morbidity and mortality weekly report 2021 9 (36) 1242-1244>
This report summarizes NWSS activities and describes innovative applications of wastewater surveillance data by two states, which have included generating alerts to local jurisdictions, allocating mobile testing resources, evaluating irregularities in traditional surveillance, refining health messaging, and forecasting clinical resource needs. NWSS complements traditional surveillance and enables health departments to intervene earlier with focused support in communities experiencing increasing concentrations of SARS-CoV-2 in wastewater.
SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis
TB Hoeg et al, MEDRXIV, September 9, 2021>
Post-vaccination cardiac adverse effects (CAE) rate was highest in young boys aged 12-15 following dose two. For boys 12-17 without medical comorbidities, the likelihood of post vaccination dose two CAE is 162.2 and 94.0/million respectively. This incidence exceeds their expected 120-day COVID-19 hospitalization rate at both moderate (August 21, 2021 rates) and high COVID-19 hospitalization incidence.
Non-Genomics Precision Health
Measurement of respiratory rate using wearable devices and applications to COVID-19 detection
A Natarajan et al, NPJ Digital Medicine, September 25, 2021
We show that heart rate enabled wearable devices can be used to measure respiratory rate. Respiration modulates the heart rate creating excess power in the heart rate variability at a frequency equal to the respiratory rate, a phenomenon known as respiratory sinus arrhythmia. We isolate this component from the power spectral density of the heart beat interval time series, and show that the respiratory rate thus estimated is in good agreement with a validation dataset.
Population Immunity Against COVID-19 in the United States
SM Moghadas et al, Ann Int Med, September 14, 2021
Using age-specific IFR estimates from the Centers for Disease Control and Prevention, it was estimated that as of 15 July 2021, 114.9 (95% credible interval [CrI], 103.2 to 127.4) million persons had been infected with SARS-CoV-2 in the United States. The mean overall population immunity was 62.0% (CrI, 58.4% to 66.4%). Adults aged 65 years or older were estimated to have the highest immunity level (77.2% [CrI, 76.2% to 78.6%]), and children younger than 12 years had the lowest immunity level (17.9% [CrI, 14.4% to 21.9%]).
Contact tracing is an imperfect tool for controlling COVID-19 transmission and relies on population adherence
EL Davis et al, Nature Communications, September 13, 2021
Emerging evidence suggests that contact tracing has had limited success in the UK in reducing the R number across the COVID-19 pandemic. We investigate potential pitfalls and areas for improvement by extending an existing branching process contact tracing model, adding diagnostic testing and refining parameter estimates. Our results demonstrate that reporting and adherence are the most important predictors of program impact but tracing coverage and speed plus diagnostic sensitivity also play an important role.
News, Reviews and Commentaries
New Evidence on SARS-CoV-2 Vaccine Boosters
EJ Rubin et al, NEJM, September 16, 2021
he continuing spread of SARS-CoV-2 remains a Public Health Emergency of International Concern. What physicians need to know about transmission, diagnosis, and treatment of Covid-19 is the subject of ongoing updates from infectious disease experts. In this audio interview conducted on September 14, 2021, the editors discuss new studies that measure the effectiveness of booster doses in raising antibody levels and protecting against Covid-19.
Pfizer Analysis Makes Case For COVID Vaccine Booster
S Hensley, NPR, September 15, 2021
How patient data underpin COVID-19 research
M Renault, Nature, September 14, 2021
Tracking the coronavirus SARS-CoV-2, developing treatments and testing vaccines have relied on access to the health data of millions of people. This massive trove could be used to understand other diseases, but not everyone is convinced.
Digital exposure tools: Design for privacy, efficacy, and equity
S Landau, Science, September 10, 2021
Use of smartphone-based digital contact- tracing apps has shown promise in responding to the COVID-19 pandemic. But such apps can reveal very personal information; thus, their use raises important societal questions, not just during the current pandemic but as we learn and prepare for other inevitable outbreaks ahead. Can privacy-protective versions of such apps work? Are they efficacious? Because the apps influence who is notified of exposure and who gets tested—and possibly treated—we need to consider the apps in the context of health care equity.
Vaccines Will Not Produce Worse Variants
D Lowe, Science, September 10, 2021
There is every reason at both the population and individual level to expect that vaccination will strongly decrease the chances of a more dangerous coronavirus strain taking hold. If we'd had them earlier and were able to deploy them quickly and widely enough, we never would have seen the Delta variant in the first place.
The next phase of SARS-CoV-2 surveillance: real-time molecular epidemiology
BBO Munnink et al, Nature Medicine, September 9, 2021
To prepare for the next phase of the pandemic, a systematic approach is needed to link global genomic surveillance and timely assessment of the phenotypic characteristics of novel variants, which will support the development and updating of diagnostics, vaccines, therapeutics and nonpharmaceutical interventions. This Review summarizes the current knowledge on key viral mutations and variants and looks to the next phase of surveillance of the evolving pandemic.
Mechanisms underlying host defense and disease pathology in response to severe acute respiratory syndrome (SARS)-CoV2 infection: insights from inborn errors of immunity.
Tangye Stuart et al. Current opinion in allergy and clinical immunology 2021 9
Genetic, serological and cohort studies have provided key findings regarding host defense against SARS-CoV2 infection, and mechanisms of disease pathogenesis. Remarkably, the risk factors, severity of disease, and case fatality rate following SARS-CoV2 infection in patients with IEI were not too dissimilar to that observed for the general population. However, the type I interferon (IFN) signaling pathway - activated in innate immune cells in response to viral sensing - is critical for anti-SARS-CoV2 immunity. Indeed, genetic variants or autoAbs affecting type I IFN function account for up to 20% of all cases of life-threatening COVID-19.