Comparative Household Secondary Attack Rates associated with B.1.1.7, B.1.351, and P.1 SARS-CoV-2 Variants
TL;DR: In this paper, the authors compared the secondary attack rates of SARS-COV-2 mutations and variants in the Canadas largest province of Ontario, using a previously validated household-based approach.
Abstract: BackgroundThe emergence of SARS-CoV-2 variants associated with increased transmissibility are driving a 3rd global surge in COVID-19 incidence. There are currently few reliable estimates for the P.1 and B.1.351 lineages. We sought to compare the secondary attack rates of SARS-COV-2 mutations and variants in Canadas largest province of Ontario, using a previously validated household-based approach. MethodsWe identified individuals with confirmed SARS-CoV-2 infection in Ontarios provincial reportable disease surveillance system. Cases were grouped into households based on reported residential address. Index cases had the earliest of symptom onset in the household. Household secondary attack rate was defined as the percentage of household contacts identified as secondary cases within 1-14 days after the index case. ResultsWe identified 26,888 index household cases during the study period. Among these, 7,555 (28%) were wild-type, 17,058 (63%) were B.1.1.7, 1674 (6%) were B.1.351 or P.1, and 601 (2%) were non-VOC mutants (Table 1). The secondary attack rates, according to index case variant were as follows: 20.2% (wild-type), 25.1% (B.1.1.7), 27.2% (B.1.351 or P.1), and 23.3% (non-VOC mutants). In adjusted analyses, we found that B.1.1.7, B.1.351, and P.1 index cases had the highest transmissibility (presumptive B.1.1.7 ORadjusted=1.49, 95%CI 1.36, 1.64; presumptive B.1.351 or P.1 ORadjusted=1.60, 95%CI 1.37, 1.87). O_TBL View this table: org.highwire.dtl.DTLVardef@1f1a4e9org.highwire.dtl.DTLVardef@181f042org.highwire.dtl.DTLVardef@1c483fborg.highwire.dtl.DTLVardef@b4fba0org.highwire.dtl.DTLVardef@1f3d626_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO O_TABLECAPTIONSecondary attack rates of persons infected with SARS-CoV-2, March 1 to April 17. C_TABLECAPTION C_TBL DiscussionSubstantially higher transmissibility associated with variants will make control of SARS-CoV-2 more difficult, reinforcing the urgent need to increase vaccination rates globally.
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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: Key information is examined and provided on SARS-CoV-2 VOCs, including their transmissibility, infectivity rate, disease severity, affinity for angiotensin-converting enzyme 2 (ACE2) receptors, viral load, reproduction number, vaccination effectiveness, and vaccine breakthrough.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that belongs to the coronavirus family and is the cause of coronavirus disease 2019 (COVID-19). As of May 2022, it had caused more than 500 million infections and more than 6 million deaths worldwide. Several vaccines have been produced and tested over the last two years. The SARS-CoV-2 virus, on the other hand, has mutated over time, resulting in genetic variation in the population of circulating variants during the COVID-19 pandemic. It has also shown immune-evading characteristics, suggesting that vaccinations against these variants could be potentially ineffective. The purpose of this review article is to investigate the key variants of concern (VOCs) and mutations of the virus driving the current pandemic, as well as to explore the transmission rates of SARS-CoV-2 VOCs in relation to epidemiological factors and to compare the virus’s transmission rate to that of prior coronaviruses. We examined and provided key information on SARS-CoV-2 VOCs in this study, including their transmissibility, infectivity rate, disease severity, affinity for angiotensin-converting enzyme 2 (ACE2) receptors, viral load, reproduction number, vaccination effectiveness, and vaccine breakthrough.
19 citations
TL;DR: In this paper , a serological definition of reinfection (reactivity boosting following waning like a V-shaped curve in both assays or three spaced boostings), probable (two separate boosting events) and possible (reinfection detected by only one assay) reinfections was proposed.
Abstract: The city of Manaus, north Brazil, was stricken by a second epidemic wave of SARS-CoV-2 despite high seroprevalence estimates, coinciding with the emergence of the Gamma (P.1) variant. Reinfections were postulated as a partial explanation for the second surge. However, accurate calculation of reinfection rates is difficult when stringent criteria as two time-separated RT-PCR tests and/or genome sequencing are required. To estimate the proportion of reinfections caused by Gamma during the second wave in Manaus and the protection conferred by previous infection, we identified anti-SARS-CoV-2 antibody boosting in repeat blood donors as a mean to infer reinfection.We tested serial blood samples from unvaccinated repeat blood donors in Manaus for the presence of anti-SARS-CoV-2 IgG antibodies using two assays that display waning in early convalescence, enabling the detection of reinfection-induced boosting. Donors were required to have three or more donations, being at least one during each epidemic wave. We propose a strict serological definition of reinfection (reactivity boosting following waning like a V-shaped curve in both assays or three spaced boostings), probable (two separate boosting events) and possible (reinfection detected by only one assay) reinfections. The serial samples were used to divide donors into six groups defined based on the inferred sequence of infection and reinfection with non-Gamma and Gamma variants.From 3655 repeat blood donors, 238 met all inclusion criteria, and 223 had enough residual sample volume to perform both serological assays. We found 13.6% (95% CI 7.0-24.5%) of all presumed Gamma infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections, these percentages increase respectively to 22.7% (95% CI 14.3-34.2%) and 39.3% (95% CI 29.5-50.0%). Previous infection conferred a protection against reinfection of 85.3% (95% CI 71.3-92.7%), decreasing to respectively 72.5% (95% CI 54.7-83.6%) and 39.5% (95% CI 14.1-57.8%) if probable and possible reinfections are included.Reinfection by Gamma is common and may play a significant role in epidemics where Gamma is prevalent, highlighting the continued threat variants of concern pose even to settings previously hit by substantial epidemics.
14 citations
TL;DR: In this article, the reinfections induce a recrudescence (or boosting) of plasma anti-N IgG antibody levels, yielding a V-shaped time series of antibody reactivity levels, indicating that reinfection due to P.1 is common and more frequent than what has been detected by traditional epidemiologic, molecular and genomic surveillance of clinical cases.
Abstract: The city of Manaus, north Brazil, was stricken by a severe epidemic of SARS-Cov-2 in March 2020, reaching a seroprevalence of 76% by October 2020. Nevertheless, in late November an abrupt increase in hospitalizations and deaths hit Manaus, causing higher number of deaths compared to the first epidemic wave. It has been hypothesized that virus lineages circulating in the second wave, namely the P.1 variant of concern first detected in early December in Manaus, could be better at evading immunity generated in response to previous infection with other lineages. In order to estimate the reinfection rate during the resurgence of SARS-CoV-2 in Manaus, we tested serial samples from 238 unvaccinated repeat blood donors using a SARS-CoV-2 anti-N IgG chemiluminescence microparticle assay. Blood donors were divided into six groups that reflected the inferred sequence of infection and reinfection with non-P.1 and P.1 variants. We assumed that reinfections induce a recrudescence (or "boosting") of plasma anti-N IgG antibody levels, yielding a V-shaped time series of antibody reactivity levels. We infer that 16.9% (95% CI [9.48%, 28.5%]) of all presumed P.1 infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections (defined by considering the time period when the antibody levels are expected to grow after recovery and the range of half-lives for antibody waning after seroconversion), these percentages increase respectively to 25.8% (95% CI [16.7%, 37.4%]), and 31.0% (95% CI [21.4%, 42.5%]). Our data suggest that reinfection due to P.1 is common and more frequent than what has been detected by traditional epidemiologic, molecular and genomic surveillance of clinical cases.
11 citations
TL;DR: By repeated saliva self-sampling combined with NPS, OPS, and serology, this work found the highest SARS-CoV-2 household transmission rates reported to date.
Abstract: Abstract Background Understanding the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) household transmission is important for adequate infection control measures in this ongoing pandemic. Methods Households were enrolled upon a polymerase chain reaction–confirmed index case between October and December 2020, prior to the coronavirus disease 2019 vaccination program. Saliva samples were obtained by self-sampling at days 1, 3, 5, 7, 10, 14, 21, 28, 35, and 42 from study inclusion. Nasopharyngeal swabs (NPS) and oropharyngeal swabs (OPS) were collected by the research team at day 7 and capillary blood samples at day 42. Household secondary attack rate (SAR) and per-person SAR were calculated based on at least 1 positive saliva, NPS, OPS, or serum sample. Whole genome sequencing was performed to investigate the possibility of multiple independent SARS-CoV-2 introductions within a household. Results Eighty-five households were included consisting of 326 (unvaccinated) individuals. Comparable numbers of secondary cases were identified by saliva (133/241 [55.2%]) and serum (127/213 [59.6%]). The household SAR was 88.2%. The per-person SAR was 64.3%. The majority of the secondary cases tested positive in saliva at day 1 (103/150 [68.7%]). Transmission from index case to household member was not affected by age or the nature of their relationship. Phylogenetic analyses suggested a single introduction for the investigated households. Conclusions Households have a pivotal role in SARS-CoV-2 transmission. By repeated saliva self-sampling combined with NPS, OPS, and serology, we found the highest SARS-CoV-2 household transmission rates reported to date. Salivary (self-) sampling of adults and children is suitable and attractive for near real-time monitoring of SARS-CoV-2 transmission in this setting.
7 citations
References
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TL;DR: The SARS-CoV-2 lineage B.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020 as mentioned in this paper.
Abstract: The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic diversity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England; extrapolation to other transmission contexts therefore requires caution.
547 citations
TL;DR: In this article, the spread of the B.1.7 SARs-CoV-2 variant in the Greater Toronto Area over 4 months was determined by tracking S-gene target failure as marker.
Abstract: This study determined the spread of the B.1.1.7 SARs-CoV-2 variant in the Greater Toronto Area over 4 months by tracking S-gene target failure as marker.
82 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
TL;DR: In this article, a propensity-score matched cohort was derived to calculate adjusted estimates of the secondary attack rate for VOC index cases in households and showed that asymptomatic and pre-symptomatic transmission may be of particular importance for index cases.
Abstract: IMPORTANCEHigher secondary attack rates related to variant of concern (VOC) index cases have been reported, but have not been explored within households, which continue to be an important source of coronavirus disease 2019 (COVID-19) transmission OBJECTIVETo compare secondary attack rates in households with VOC versus non-VOC index cases DESIGNA retrospective cohort study of household index cases reported from February 7 - 27, 2021 A propensity-score matched cohort was derived to calculate adjusted estimates SETTINGOntario, Canada PARTICIPANTSA population-based cohort of all private households with index cases We excluded cases in congregate settings, as well as households with one individual or with >1 case with the same earliest symptom onset date EXPOSUREVOC status, defined as either individuals confirmed as B117 using whole genome sequencing or those that screened positive for the N501Y mutation using real-time PCR MAIN OUTCOME AND MEASUREHousehold secondary attack rate, defined as the number of household secondary cases that occurred 1-14 days after the index case divided by the total number of household secondary contacts RESULTSWe included 1,259 index VOC and non-VOC cases in the propensity score-matched analysis The secondary attack rate for VOC index cases in this matched cohort was 131 times higher than non-VOC index cases (RR=131, 95%CI 114-149), similar to the unadjusted estimate In stratified analyses, the higher secondary attack rate for VOC compared to non-VOC index cases was accentuated for asymptomatic index cases (RR=191, 95% CI 096-380) and presymptomatic cases (RR=341, 95%CI 113-1026) CONCLUSIONS AND RELEVANCEThis study provides strong evidence of increased transmissibility in households due to VOCs and suggests that asymptomatic and pre-symptomatic transmission may be of particular importance for VOCs Our study suggests that more aggressive public health measures will be needed to control VOCs and that ongoing research is needed to understand mechanisms of VOC transmissibility to curb their associated morbidity and mortality
7 citations