Superspreading of SARS-CoV-2: a systematic review and meta-analysis of event attack rates and individual transmission patterns (preprint)

SARS-CoV-2 superspreading occurs when transmission is highly efficient and/or an individual infects many others, contributing to rapid spread. To better quantify heterogeneity in SARS-CoV-2 transmission, particularly superspreading, we performed a systematic review of transmission events with data on secondary attack rates or contact tracing of individual index cases published before September 2021, prior to emergence of variants of concern and widespread vaccination. We reviewed 592 distinct events and 9,883 index cases from 491 papers. Meta-analysis of secondary attack rates identified substantial heterogeneity across 12 event types/settings, with the highest transmission (25-35%) in co-living situations including households, nursing homes, and other congregate housing. Among index cases, 67% produced zero secondary cases and only 3% (287) infected >5 secondary cases ("superspreaders"). The highest percentage of superspreaders was among symptomatic individuals, individuals aged 49-64 years, and individuals with over 100 total contacts. However, only 55% of index cases reported age, sex, symptoms, real-time PCR cycle threshold values, or total contacts. Despite the limitations, our review highlighted that SARS-CoV-2 superspreading is more likely in settings with prolonged close contact and among symptomatic adults with many contacts. Enhanced reporting on transmission events and contact tracing could help explain heterogeneity and facilitate control efforts.

Protective effectiveness of prior SARS-CoV-2 infection and hybrid immunity against Omicron infection and severe disease: a systematic review and meta-regression (preprint)

Background We aimed to systematically review the magnitude and duration of the protective effectiveness of prior infection (PE) and hybrid immunity (HE) against Omicron infection and severe disease. Methods We searched pre-print and peer-reviewed electronic databases for controlled studies from January 1, 2020, to June 1, 2022. Risk of bias (RoB) was assessed using the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I)-Tool. We used random-effects meta-regression to estimate the magnitude of protection at 1-month intervals and the average change in protection since the last vaccine dose or infection from 3 months to 6 or 12 months. We compared our estimates of PE and HE to previously published estimates of the magnitude and durability of vaccine effectiveness (VE) against Omicron. Findings Eleven studies of prior infection and 15 studies of hybrid immunity were included. For prior infection, there were 97 estimates (27 at moderate RoB and 70 at serious RoB), with the longest follow up at 15 months. PE against hospitalization or severe disease was 82.5% [71.8-89.7%] at 3 months, and 74.6% [63.1-83.5%] at 12 months. PE against reinfection was 65.2% [52.9-75.9%] at 3 months, and 24.7% [16.4-35.5%] at 12 months. For HE, there were 153 estimates (78 at moderate RoB and 75 at serious RoB), with the longest follow up at 11 months for primary series vaccination and 4 months for first booster vaccination. Against hospitalization or severe disease, HE involving either primary series vaccination or first booster vaccination was consistently >95% for the available follow up. Against reinfection, HE involving primary series vaccination was 69.0% [58.9-77.5%] at 3 months after the most recent infection or vaccination, and 41.8% [31.5-52.8%] at 12 months, while HE involving first booster vaccination was 68.6% [58.8-76.9%] at 3 months, and 46.5% [36.0-57.3%] at 6 months. Against hospitalization or severe disease at 6 months, hybrid immunity with first booster vaccination (effectiveness 95.3% [81.9-98.9%]) or with primary series alone (96.5% [90.2-98.8%]) provided significantly greater protection than prior infection alone (80.1% [70.3-87.2%]), first booster vaccination alone (76.7% [72.5-80.4%]), or primary series alone (64.6% [54.5-73.6%]). Results for protection against reinfection were similar. Interpretation Prior infection and hybrid immunity both provided greater and more sustained protection against Omicron than vaccination alone. All protection estimates waned quickly against infection but remained high for hospitalisation or severe disease. Individuals with hybrid immunity had the highest magnitude and durability of protection against all outcomes, reinforcing the global imperative for vaccination.

Low testing rates limit the ability of genomic surveillance programs to monitor SARS-CoV-2 variants: a mathematical modelling study (preprint)

Background Genomic surveillance is essential for monitoring the emergence and spread of SARS-CoV-2 variants. SARS-CoV-2 diagnostic testing is the starting point for SARS-CoV-2 genomic sequencing. However, testing rates in many low- and middle-income countries (LMICs) are low (mean = 27 tests/100,000 people/day) and global testing rates are falling in the post-crisis phase of the pandemic, leading to spatiotemporal biases in sample collection. Various public health agencies and academic groups have produced recommendations on sample sizes and sequencing strategies for effective genomic surveillance. However, these recommendations assume very high volumes of diagnostic testing that are currently well beyond reach in most LMICs. Methods To investigate how testing rates, sequencing strategies and the degree of spatiotemporal bias in sample collection impact variant detection and monitoring outcomes, we used an individual-based model to simulate COVID-19 epidemics in a prototypical LMIC. Within the model, we simulated a range of testing rates, accounted for likely testing demand and applied various genomic surveillance strategies, including sentinel surveillance. Findings Diagnostic testing rates play a substantially larger role in monitoring the prevalence and emergence of new variants than the proportion of samples sequenced. To enable timely detection and monitoring of emerging variants, programs should achieve average testing rates of at least 100 tests/100,000 people/day and sequence 5-10% of test-positive specimens, which may be accomplished through sentinel or other routine surveillance systems. Under realistic assumptions, this averages to ~10 samples for sequencing/1,000,000 people/week. Interpretation For countries where testing capacities are low and sample collection is spatiotemporally biased, surveillance programs should prioritize investments in wider access to diagnostic testing to enable more representative sampling, ahead of simply increasing quantities of sequenced samples. Funding European Research Council, the Rockefeller Foundation, and the Governments of Germany, Canada, UK, Australia, Norway, Saudi Arabia, Kuwait, Netherlands and Portugal.

Transmission of SARS-CoV-2 in standardised First Few X cases and household transmission investigations: a systematic review and meta-analysis (preprint)

First Few X cases (FFX) investigations and Household transmission investigations (HHTI) are essential epidemiological tools for early characterisation of novel infectious pathogens and their variants. We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies HHTI protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines (PROSPERO registration: CRD42021260065). We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for Unity-aligned FFX and HHTI published between 1 December 2019 and 26 July 2021. Standardised early results were shared by WHO Unity Studies Collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses. Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by WHO Unity Studies collaborators) were retained in the systematic review and 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2%-90% (95% prediction interval: 3%-71%; I2 = 99.7%); I2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. The large, unexplained variance in hSAR estimates emphasises the need for improved standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.

SARS-CoV-2 infection in Africa: A systematic review and meta-analysis of standardised seroprevalence studies, from January 2020 to December 2021 (preprint)

IntroductionEstimating COVID-19 cumulative incidence in Africa remains problematic due to challenges in contact tracing, routine surveillance systems and laboratory testing capacities and strategies. We undertook a meta-analysis of population-based seroprevalence studies to estimate SARS-CoV-2 seroprevalence in Africa to inform evidence-based decision making on Public Health and Social Measures (PHSM) and vaccine strategy. MethodsWe searched for seroprevalence studies conducted in Africa published 01-01-2020 to 30-12-2021 in Medline, Embase, Web of Science, and Europe PMC (preprints), grey literature, media releases and early results from WHO Unity studies. All studies were screened, extracted, assessed for risk of bias and evaluated for alignment with the WHO Unity protocol for seroepidemiological investigations. We conducted descriptive analyses of seroprevalence and meta-analysed seroprevalence differences by demographic groups, place and time. We estimated the extent of undetected infections by comparing seroprevalence and cumulative incidence of confirmed cases reported to WHO. PROSPERO: CRD42020183634. ResultsWe identified 54 full texts or early results, reporting 151 distinct seroprevalence studies in Africa Of these, 95 (63%) were low/moderate risk of bias studies. SARS-CoV-2 seroprevalence rose from 3.0% [95% CI: 1.0-9.2%] in Q2 2020 to 65.1% [95% CI: 56.3-73.0%] in Q3 2021. The ratios of seroprevalence from infection to cumulative incidence of confirmed cases was large (overall: 97:1, ranging from 10:1 to 958:1) and steady over time. Seroprevalence was highly heterogeneous both within countries - urban vs. rural (lower seroprevalence for rural geographic areas), children vs. adults (children aged 0-9 years had the lowest seroprevalence) - and between countries and African sub-regions (Middle, Western and Eastern Africa associated with higher seroprevalence). ConclusionWe report high seroprevalence in Africa suggesting greater population exposure to SARS-CoV-2 and protection against COVID-19 disease than indicated by surveillance data. As seroprevalence was heterogeneous, targeted PHSM and vaccination strategies need to be tailored to local epidemiological situations.

Global disparities in SARS-CoV-2 genomic surveillance (preprint)

Genomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes >21 days after sample collection, and 77% of low and middle income countries sequenced <0.5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT <21 days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness. One-Sentence SummarySocioeconomic inequalities impacted the SARS-CoV-2 genomic surveillance, and undermined the global pandemic preparedness.

Mask Use in Community Settings in the Context of COVID-19: A Systematic Review of Ecological Data (preprint)

Background: The wearing of medical and non-medicaal masks by the general public in community settings is one intervention that is important for the reduction of SARS-COV-2 transmission, and has been the subject of considerable research, policy, advocacy and debate. Several observational studies have used ecological (population-level) data to assess the effect of masks on transmission, hospitalization, and mortality at the region or community level. Methods: We undertook this systematic review to summarize the study designs, outcomes, and key quality indicators of using ecological data to evaluate the association between mask wearing and COVID-19 outcomes. We searched the World Health Organization (WHO) COVID-19 global literature database up to 4 March 2021 for studies reporting the impact of mask use in community settings on outcomes related to SARS-COV-2 transmission using ecologic data. Findings: 21 articles were identified that analysed ecological data to assess the protective effect of policies mandating community mask wearing. All studies reported SARS-COV-2 benefits in terms of reductions in either the incidence, hospitalization, or mortality, or a combination of these outcomes. Few studies assessed compliance to mask wearing policies or controlled for the possible influence of other preventive measures such as hand hygiene and physical distancing, and information about compliance to these policies was lacking. Interpretation: Ecological studies have been cited as evidence to advocate for the adoption of universal masking policies. The studies summarized by this review suggest that community mask policies may reduce the population-level burden of SARS-CoV-2. Methodological limitations, in particular controlling for the actual practice of mask wearing and other preventive policies make it difficult to determine causality. There are several important limitations to consider for improving the validity of ecological data.Funding Statement: None.Declaration of Interests: None.