ABSTRACT
Background Increasing the availability of antigen rapid diagnostic tests (Ag-RDTs) in low- and middle-income countries (LMICs) is key to alleviating global SARS-CoV-2 testing inequity (median testing rate in December 2021-March 2022 when the Omicron variant was spreading in multiple countries; high-income countries=600 tests/100,000 people/day; LMICs=14 tests/ 100,000 people/day). However, target testing levels and effectiveness of asymptomatic community screening to impact SARS-CoV-2 transmission in LMICs are unclear. Methods We used PATAT, an LMIC-focused agent-based model to simulate COVID-19 epidemics, varying the amount of Ag-RDTs available for symptomatic testing at healthcare facilities and asymptomatic community testing in different social settings. We assumed that testing was a function of access to healthcare facilities and availability of Ag-RDTs. We explicitly modelled symptomatic testing demand from non-SARS-CoV-2 infected individuals and measured impact based on the number of infections averted due to test-and-isolate. Findings Testing symptomatic individuals yields greater benefits than any asymptomatic community testing strategy until most symptomatic individuals who sought testing have been tested. Meeting symptomatic testing demand likely requires ~200-400 tests/100,000 people/day on average as symptomatic testing demand is highly influenced by non-SARS-CoV-2 infected individuals. After symptomatic testing demand is satisfied, excess tests to proactively screen for asymptomatic infections among household members yields the largest additional infections averted. Interpretation Testing strategies aimed at reducing transmission should prioritize symptomatic testing and incentivizing test-positive individuals to adhere to isolation to maximize effectiveness.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
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.
Subject(s)
COVID-19 , Kallmann SyndromeABSTRACT
Variants of concern (VOCs) of SARS-CoV-2 have caused resurging waves of infections worldwide. In the Netherlands, Alpha, Beta, Gamma and Delta variants circulated widely between September 2020 and August 2021. To understand how various control measures had impacted the spread of these VOCs, we analyzed 39,844 SARS-CoV-2 genomes collected under the Dutch national surveillance program. We found that all four VOCs were introduced before targeted flight restrictions were imposed on countries where the VOCs first emerged. Importantly, foreign introductions, predominantly from other European countries, continued during these restrictions. Our findings show that flight restrictions had limited effectiveness in deterring VOC introductions due to the strength of regional land travel importation risks. We also found that the Alpha and Delta variants largely circulated more populous regions with international connections after their respective introduction before asymmetric bidirectional transmissions occurred with the rest of the country and the variant dominated infections in the Netherlands. As countries consider scaling down SARS-CoV-2 surveillance efforts in the post-crisis phase of the pandemic, our results highlight that robust surveillance in regions of early spread is important for providing timely information for variant detection and outbreak control.
ABSTRACT
Large-scale vaccination campaigns have prevented countless SARS-CoV-2 infections, hospitalizations and deaths. However, the emergence of variants that escape from immunity challenges the effectiveness of current vaccines. Given this continuing evolution, an important question is when and how to update SARS-CoV-2 vaccines to antigenically match circulating variants, similar to seasonal influenza viruses where antigenic drift necessitates periodic vaccine updates. Here, we studied SARS-CoV-2 antigenic drift by assessing neutralizing activity against variants-of-concern (VOCs) of a unique set of sera from patients infected with a range of VOCs. Infections with ancestral or Alpha strains induced the broadest immunity, while individuals infected with other VOCs had more strain-specific responses. Omicron was substantially resistant to neutralization by sera elicited by all other variants. Antigenic cartography revealed that all VOCs preceding Omicron belong to one antigenic cluster, while Omicron forms a new antigenic cluster associated with immune escape and likely requiring vaccine updates to ensure vaccine effectiveness.
Subject(s)
Severe Acute Respiratory SyndromeABSTRACT
Background The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose sparing strategies, particularly single vaccine dosing of individuals with prior SARS-CoV-2 infection. Methods We evaluated SARS-CoV-2 specific antibody responses following a single-dose of BNT162b2 (Pfizer-BioNTech) mRNA vaccine in 155 previously SARS-CoV-2-infected individuals participating in a population-based prospective cohort study of COVID-19 patients. Participants varied widely in age, comorbidities, COVID-19 severity and time since infection, ranging from 1 to 15 months. Serum antibody titers were determined at time of vaccination and one week after vaccination. Responses were compared to those in SARS-CoV-2-naive health care workers after two BNT162b2 mRNA vaccine doses. Results Within one week of vaccination, IgG antibody levels to virus spike and RBD proteins increased 27 to 29-fold and neutralizing antibody titers increased 12-fold, exceeding titers of fully vaccinated SARS-CoV-2-naive controls (95% credible interval (CrI): 0.56 to 0.67 v. control 95% CrI: -0.16 to -0.02). Pre-vaccination neutralizing antibody titers had the largest positive mean effect size on titers following vaccination (95% CrI (0.16 to 0.45)). COVID-19 severity, the presence of comorbidities and the time interval between infection and vaccination had no discernible impact on vaccine response. Conclusion A single dose of BNT162b2 mRNA vaccine up to 15 months after SARS-CoV-2 infection provides neutralizing titers exceeding two vaccine doses in previously uninfected individuals. These findings support wide implementation of a single-dose mRNA vaccine strategy after prior SARS-CoV-2 infection.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
BACKGROUND It is unclear how, when and where health care workers (HCW) working in hospitals are infected with SARS-CoV-2. METHODS Prospective cohort study comprising 4-weekly measurement of SARS-CoV-2 specific antibodies and questionnaires from March to June 2020. We compared SARS-CoV-2 incidence between HCW working in Covid-19 patient care, HCW working in non-Covid-19 patient care and HCW not in patient care. Phylogenetic analyses of SARS-CoV-2 samples from patients and HCW were performed to identify potential transmission clusters. RESULTS We included 801 HCW: 439 in the Covid-19 patient care group, 164 in the non-Covid-19 patient care group and 198 in the no patient care group. SARS-CoV-2 incidence was highest in HCW working in Covid-19 patient care (13.2%), as compared with HCW in non-Covid-19 patient care (6.7%, hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.2 to 4.3) and in HCW not working in patient care (3.6%, HR 3.9, 95% CI 1.8 to 8.6). Within the group of HCW caring for Covid-19 patients, SARS-CoV-2 cumulative incidence was highest in HCW working on Covid-19 wards (25.7%), as compared with HCW working on intensive care units (7.1%, HR 3.6, 95% CI 1.9 to 6.9), and HCW working in the emergency room (8.0%, HR 3.3, 95% CI 1.5 to 7.1). Phylogenetic analyses on Covid-19 wards identified multiple potential HCW-to-HCW transmission clusters while no patient-to-HCW transmission clusters were identified. CONCLUSIONS HCW working on Covid-19 wards are at increased risk for nosocomial SARS-CoV-2 infection, with an important role for HCW-to-HCW transmission.