Increased household secondary attacks rates with Variant of Concern SARS-CoV-2 index cases.
TL;DR: In this paper, the authors compared secondary attack rates in households with B.1.7 variant of concern (VOC) versus non-VOC index cases in a matched cohort in Ontario, Canada.
Abstract: We compared secondary attack rates in households with B.1.1.7 variant of concern (VOC) versus non-VOC index cases in a matched cohort in Ontario, Canada. The secondary attack rate for VOC index cases was 1.31 times higher than non-VOC index cases. This increase was particularly accentuated for asymptomatic or presymptomatic index cases.
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02 Aug 2021
TL;DR: A previous systematic review and meta-analysis of household transmission of SARS-CoV-2 that summarized 54 published studies through October 19, 2020, found an overall secondary attack rate (SAR) of 16.6% (95% CI, 14.0%-19.3%).
Abstract: Importance A previous systematic review and meta-analysis of household transmission of SARS-CoV-2 that summarized 54 published studies through October 19, 2020, found an overall secondary attack rate (SAR) of 16.6% (95% CI, 14.0%-19.3%). However, the understanding of household secondary attack rates for SARS-CoV-2 is still evolving, and updated analysis is needed. Objective To use newly published data to further the understanding of SARS-CoV-2 transmission in the household. Data sources PubMed and reference lists of eligible articles were used to search for records published between October 20, 2020, and June 17, 2021. No restrictions on language, study design, time, or place of publication were applied. Studies published as preprints were included. Study selection Articles with original data that reported at least 2 of the following factors were included: number of household contacts with infection, total number of household contacts, and secondary attack rates among household contacts. Studies that reported household infection prevalence (which includes index cases), that tested contacts using antibody tests only, and that included populations overlapping with another included study were excluded. Search terms were SARS-CoV-2 or COVID-19 with secondary attack rate, household, close contacts, contact transmission, contact attack rate, or family transmission. Data extraction and synthesis Meta-analyses were performed using generalized linear mixed models to obtain SAR estimates and 95% CIs. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Main outcomes and measures Overall household SAR for SARS-CoV-2, SAR by covariates (contact age, sex, ethnicity, comorbidities, and relationship; index case age, sex, symptom status, presence of fever, and presence of cough; number of contacts; study location; and variant), and SAR by index case identification period. Results A total of 2722 records (2710 records from database searches and 12 records from the reference lists of eligible articles) published between October 20, 2020, and June 17, 2021, were identified. Of those, 93 full-text articles reporting household transmission of SARS-CoV-2 were assessed for eligibility, and 37 studies were included. These 37 new studies were combined with 50 of the 54 studies (published through October 19, 2020) from our previous review (4 studies from Wuhan, China, were excluded because their study populations overlapped with another recent study), resulting in a total of 87 studies representing 1 249 163 household contacts from 30 countries. The estimated household SAR for all 87 studies was 18.9% (95% CI, 16.2%-22.0%). Compared with studies from January to February 2020, the SAR for studies from July 2020 to March 2021 was higher (13.4% [95% CI, 10.7%-16.7%] vs 31.1% [95% CI, 22.6%-41.1%], respectively). Results from subgroup analyses were similar to those reported in a previous systematic review and meta-analysis; however, the SAR was higher to contacts with comorbidities (3 studies; 50.0% [95% CI, 41.4%-58.6%]) compared with previous findings, and the estimated household SAR for the B.1.1.7 (α) variant was 24.5% (3 studies; 95% CI, 10.9%-46.2%). Conclusions and relevance The findings of this study suggest that the household remains an important site of SARS-CoV-2 transmission, and recent studies have higher household SAR estimates compared with the earliest reports. More transmissible variants and vaccines may be associated with further changes.
99 citations
TL;DR: In this article, the authors discuss the different SARS-CoV-2 variants, emphasizing variants of concern circulating the world and highlight the various mutations and how these mutations affect the characteristics of the virus.
65 citations
01 Sep 2022
TL;DR: The effects of various spike (S) protein mutations in SARS-CoV-2 and its VOC on transmissibility, illness severity, hospitalization risk, fatality rate, immunological evasion, and vaccine efficacy are compared in this review.
Abstract: In December 2019, the severe acute respiratory syndrome 2 (SARS-CoV-2) coronavirus outbreak began in Wuhan, China, and quickly spread to practically every corner of the globe, killing millions of people. SARS-CoV-2 produced numerous variants, five of which have been identified as variants of concern (VOC) by the World Health Organization (WHO) (Alpha, Beta, Gamma, Delta, and Omicron). We conducted a comparative epidemiological analysis of SARS-CoV-2 and its VOC in this paper. We compared the effects of various spike (S) protein mutations in SARS-CoV-2 and its VOC on transmissibility, illness severity, hospitalization risk, fatality rate, immunological evasion, and vaccine efficacy in this review. We also looked into the clinical characteristics of patients infected with SARS-CoV-2 and its VOC.
6 citations
TL;DR: Results support the application for a Phase 1 clinical trial of ACM-polymersome-based Covid-19 vaccine, and recombinant Beta spike protein coadministered with synthetic CpG adjuvant is evaluated.
Abstract: Current parenteral coronavirus disease 2019 (Covid-19) vaccines inadequately protect against infection of the upper respiratory tract. Additionally, antibodies generated by wild type (WT) spike-based vaccines poorly neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. To address the need for a second-generation vaccine, we have initiated a preclinical program to produce and evaluate a potential candidate. Our vaccine consists of recombinant Beta spike protein coadministered with synthetic CpG adjuvant. Both components are encapsulated within artificial cell membrane (ACM) polymersomes, synthetic nanovesicles efficiently internalized by antigen presenting cells, including dendritic cells, enabling targeted delivery of cargo for enhanced immune responses. ACM vaccine is immunogenic in C57BL/6 mice and Golden Syrian hamsters, evoking high serum IgG and neutralizing responses. Compared to an ACM-WT spike vaccine that generates predominantly WT-neutralizing antibodies, the ACM-Beta spike vaccine induces antibodies that neutralize WT and Beta viruses equally. Intramuscular (IM)-immunized hamsters are strongly protected from weight loss and other clinical symptoms after the Beta challenge but show delayed viral clearance in the upper airway. With intranasal (IN) immunization, however, neutralizing antibodies are generated in the upper airway concomitant with rapid and potent reduction of viral load. Moreover, antibodies are cross-neutralizing and show good activity against Omicron. Safety is evaluated in New Zealand white rabbits in a repeated dose toxicological study under Good Laboratory Practice (GLP) conditions. Three doses, IM or IN, at two-week intervals do not induce an adverse effect or systemic toxicity. Cumulatively, these results support the application for a Phase 1 clinical trial of ACM-polymersome-based Covid-19 vaccine (ClinicalTrials.gov identifier: NCT05385991).
4 citations
TL;DR: This prospective cohort study presents results from 258 air and 252 surface samples from the surroundings of 23 hospitalized and eight home-treated COVID-19 index patients between July 2020 and March 2021 and compares the results between the measured environments and patient factors.
Abstract: Abstract SARS‐CoV‐2 has been detected both in air and on surfaces, but questions remain about the patient‐specific and environmental factors affecting virus transmission. Additionally, more detailed information on viral sampling of the air is needed. This prospective cohort study (N = 56) presents results from 258 air and 252 surface samples from the surroundings of 23 hospitalized and eight home‐treated COVID‐19 index patients between July 2020 and March 2021 and compares the results between the measured environments and patient factors. Additionally, epidemiological and experimental investigations were performed. The proportions of qRT‐PCR‐positive air (10.7% hospital/17.6% homes) and surface samples (8.8%/12.9%) showed statistical similarity in hospital and homes. Significant SARS‐CoV‐2 air contamination was observed in a large (655.25 m3) mechanically ventilated (1.67 air changes per hour, 32.4–421 L/s/patient) patient hall even with only two patients present. All positive air samples were obtained in the absence of aerosol‐generating procedures. In four cases, positive environmental samples were detected after the patients had developed a neutralizing IgG response. SARS‐CoV‐2 RNA was detected in the following particle sizes: 0.65–4.7 μm, 7.0–12.0 μm, >10 μm, and <100 μm. Appropriate infection control against airborne and surface transmission routes is needed in both environments, even after antibody production has begun.
4 citations
References
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TL;DR: An extensive series of Monte Carlo simulations were conducted to determine the optimal caliper width for estimating differences in means (for continuous outcomes) and risk differences (for binary outcomes).
Abstract: In a study comparing the effects of two treatments, the propensity score is the probability of assignment to one treatment conditional on a subject's measured baseline covariates. Propensity-score matching is increasingly being used to estimate the effects of exposures using observational data. In the most common implementation of propensity-score matching, pairs of treated and untreated subjects are formed whose propensity scores differ by at most a pre-specified amount (the caliper width). There has been a little research into the optimal caliper width. We conducted an extensive series of Monte Carlo simulations to determine the optimal caliper width for estimating differences in means (for continuous outcomes) and risk differences (for binary outcomes). When estimating differences in means or risk differences, we recommend that researchers match on the logit of the propensity score using calipers of width equal to 0.2 of the standard deviation of the logit of the propensity score. When at least some of the covariates were continuous, then either this value, or one close to it, minimized the mean square error of the resultant estimated treatment effect. It also eliminated at least 98% of the bias in the crude estimator, and it resulted in confidence intervals with approximately the correct coverage rates. Furthermore, the empirical type I error rate was approximately correct. When all of the covariates were binary, then the choice of caliper width had a much smaller impact on the performance of estimation of risk differences and differences in means. Copyright © 2010 John Wiley & Sons, Ltd.
2,538 citations
TL;DR: A mouse model in which a SARS-CoV-2 strain was infectious and could cause an inflammatory response and moderate pneumonia is developed, and a panel of adaptive mutations potentially associated with the increased virulence are revealed.
Abstract: The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.
623 citations
01 Dec 2020
TL;DR: The findings suggest that households are and will continue to be important venues for transmission, even in areas where community transmission is reduced.
Abstract: Importance Crowded indoor environments, such as households, are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives To examine evidence for household transmission of SARS-CoV-2, disaggregated by several covariates, and to compare it with other coronaviruses. Data Source PubMed, searched through October 19, 2020. Search terms includedSARS-CoV-2orCOVID-19withsecondary attack rate,household,close contacts,contact transmission,contact attack rate, orfamily transmission. Study Selection All articles with original data for estimating household secondary attack rate were included. Case reports focusing on individual households and studies of close contacts that did not report secondary attack rates for household members were excluded. Data Extraction and Synthesis Meta-analyses were done using a restricted maximum-likelihood estimator model to yield a point estimate and 95% CI for secondary attack rate for each subgroup analyzed, with a random effect for each study. To make comparisons across exposure types, study was treated as a random effect, and exposure type was a fixed moderator. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Main Outcomes and Measures Secondary attack rate for SARS-CoV-2, disaggregated by covariates (ie, household or family contact, index case symptom status, adult or child contacts, contact sex, relationship to index case, adult or child index cases, index case sex, number of contacts in household) and for other coronaviruses. Results A total of 54 relevant studies with 77 758 participants reporting household secondary transmission were identified. Estimated household secondary attack rate was 16.6% (95% CI, 14.0%-19.3%), higher than secondary attack rates for SARS-CoV (7.5%; 95% CI, 4.8%-10.7%) and MERS-CoV (4.7%; 95% CI, 0.9%-10.7%). Household secondary attack rates were increased from symptomatic index cases (18.0%; 95% CI, 14.2%-22.1%) than from asymptomatic index cases (0.7%; 95% CI, 0%-4.9%), to adult contacts (28.3%; 95% CI, 20.2%-37.1%) than to child contacts (16.8%; 95% CI, 12.3%-21.7%), to spouses (37.8%; 95% CI, 25.8%-50.5%) than to other family contacts (17.8%; 95% CI, 11.7%-24.8%), and in households with 1 contact (41.5%; 95% CI, 31.7%-51.7%) than in households with 3 or more contacts (22.8%; 95% CI, 13.6%-33.5%). Conclusions and Relevance The findings of this study suggest that given that individuals with suspected or confirmed infections are being referred to isolate at home, households will continue to be a significant venue for transmission of SARS-CoV-2.
512 citations
TL;DR: In this article, a cohort was assembled of all laboratory-confirmed cases of COVID-19 residing in private households in Ontario, Canada, and logistic regression models were fit to determine index case characteristics and neighbourhood characteristics associated with transmission.
Abstract: BACKGROUND: Within-household transmission of SARS-CoV-2 infection has been identified as one of the main sources of spread of COVID-19 after lockdown restrictions and self-isolation guidelines are implemented. Secondary attack rates among household contacts are estimated to be five to ten times higher than among non-household contacts, but it is unclear which individuals are more prone to transmit infection within their households. METHODS: Using address matching, a cohort was assembled of all laboratory-confirmed cases of COVID-19 residing in private households in Ontario, Canada. Descriptive analyses were performed to compare characteristics of cases in households that experienced secondary transmission versus those that did not. Logistic regression models were fit to determine index case characteristics and neighbourhood characteristics associated with transmission. RESULTS: Between January and July, 2020, there were 26,714 cases of COVID-19 residing in 21,226 households. Longer testing delays (≥5 days versus 0 days OR=3.02, 95% CI: 2.53 - 3.60) and male gender (OR=1.28, 95% CI: 1.18 - 1.38) were associated with greater odds of household secondary transmission, while being a healthcare worker (OR=0.56, 95% CI: 0.50 - 0.62) was associated with lower odds of transmission. Neighbourhoods with larger average family size and a higher proportion of households with multiple persons per room were also associated with greater odds of transmission. CONCLUSIONS: It is important for individuals to get tested for SARS-CoV-2 infection as soon as symptoms appear, and to isolate away from household contacts; this is particularly important in neighbourhoods with large family sizes and/or crowded households.
17 citations