SARS-CoV-2 seroepidemiology in Mongolia, 2020–2021: a longitudinal national study

Background The COVID-19 pandemic has global impacts but is relatively understudied in developing countries. Mongolia, a lower-middle-income country, instituted strict control measures in early 2020 and avoided widespread transmission until vaccines became available in February, 2021. Mongolia achieved its 60% vaccination coverage goal by July 2021. We investigated the distribution and determinants of SARS-CoV-2 seroprevalence in Mongolia over 2020 and 2021. Methods We performed a longitudinal seroepidemiologic study aligned with WHO's Unity Studies protocols. We collected data from a panel of 5000 individuals in four rounds between October 2020 and December 2021. We selected participants through local health centres across Mongolia by age-stratified multi-stage cluster sampling. We tested serum for the presence of total antibodies against SARS-CoV-2 receptor-binding domain, and levels of anti-SARS-CoV-2 spike IgG and neutralising antibodies. We linked participant data with national mortality, COVID-19 case, and vaccination registries. We estimated population seroprevalence and vaccine uptake, as well as unvaccinated population prior-infection prevalence. Findings At the final round in late 2021, 82% (n = 4088) of participants completed follow-up. Estimated seroprevalence increased from 1.5% (95% CI: 1.2–2.0), to 82.3% (95% CI: 79.5–84.8) between late-2020 and late-2021. At the final round an estimated 62.4% (95% CI: 60.2–64.5) of the population were vaccinated, and of the unvaccinated population 64.5% (95% CI: 59.7–69.0) had been infected. Cumulative case ascertainment in the unvaccinated was 22.8% (95% CI: 19.1%–26.9%) and the overall infection-fatality ratio was 0.100% (95% CI: 0.088–0.124). Health workers had higher odds for being COVID-19 confirmed cases at all rounds. Males (1.72 (95% CI: 1.33–2.22)) and adults aged 20 and above (12.70 (95% CI: 8.14–20.26)) had higher odds for seroconverting by mid-2021. Among the seropositive, 87.1% (95% CI: 82.3%–90.8%) had SARS-CoV-2 neutralising antibodies by late 2021. Interpretation Our study enabled tracking of SARS-CoV-2 serological markers in the Mongolian population over one year. We found low SARS-CoV-2 seroprevalence in 2020 and early 2021, with seropositivity increasing over a 3-month interval in 2021 due to vaccine roll out and rapid infection of most of the unvaccinated population. Despite high seroprevalence in Mongolia amongst both vaccinated and unvaccinated individuals by end-2021, the SARS-CoV-2 Omicron immune escape variant caused a substantial epidemic. Funding 10.13039/100004423World Health Organization, WHO UNITY Studies initiative, with funding by the COVID-19 Solidarity Response Fund and the German Federal Ministry of Health (BMG) COVID-19 Research and development. The Ministry of Health, Mongolia partially funded this study.

SARS-CoV-2 seroprevalence in Mongolia: Results from a national population survey.

BACKGROUND: With the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in early 2020, Mongolia implemented rapid emergency measures and did not report local transmission until November 2020. We conducted a national seroprevalence survey to monitor the burden of SARS-CoV-2 in Mongolia in the months surrounding the first local transmission. METHODS: During October-December 2020, participants were randomly selected using age stratification and invited for interviews and blood samples at local primary health centres. We screened for total SARS-CoV-2 antibodies, followed by two-step quantitative SARS-CoV-2 IgG serology tests for positive samples. Weighted and test-adjusted seroprevalences were estimated. We used chi-square, Fisher's exact and other tests to identify variables associated with seropositivity. FINDINGS: A total of 5000 subjects were enrolled. We detected SARS-CoV-2 IgG antibodies in 72 samples. Crude seroprevalence of SARS-CoV-2 antibodies was 1·44% (95%CI,1·21-1·67). Population weighted and test-adjusted seroprevalences were 1·36% (95%CI,1·11-1·63) and 1·45% (95%CI,1·11-1·63), respectively. Age, sex, geographical, and occupational factors were not associated with seropositivity (p>0·05). Symptoms and signs within past 3 months and seropositivity were not associated at the time of the survey (p>0·05). INTERPRETATION: SARS-CoV-2 seroprevalence in Mongolia was low in the first year of the pandemic potentially due to strong public health measures, including border restrictions, educational facilities closure, earlier adoption of mask-wearing and others. Our findings suggest large-scale community transmission could not have occurred up to November 2020 in Mongolia. Additional serosurveys are needed to monitor the local pandemic dynamic and estimate how far from herd immunity Mongolia will be following-up with vaccination programme in 2021 and 2022. FUNDING: World Health Organisation, WHO UNITY Studies initiative, with funding by the COVID-19 Solidarity Response Fund and the German Federal Ministry of Health (BMG) COVID-19 Research and development. TRANSLATION: Cyrillic and Traditional Mongolian translation of abstract is available on appendix section.

SARS-CoV-2 seroepidemiology in Mongolia, 2020-2021: a longitudinal national study.

Background: The COVID-19 pandemic has global impacts but is relatively understudied in developing countries. Mongolia, a lower-middle-income country, instituted strict control measures in early 2020 and avoided widespread transmission until vaccines became available in February, 2021. Mongolia achieved its 60% vaccination coverage goal by July 2021. We investigated the distribution and determinants of SARS-CoV-2 seroprevalence in Mongolia over 2020 and 2021. Methods: We performed a longitudinal seroepidemiologic study aligned with WHO's Unity Studies protocols. We collected data from a panel of 5000 individuals in four rounds between October 2020 and December 2021. We selected participants through local health centres across Mongolia by age-stratified multi-stage cluster sampling. We tested serum for the presence of total antibodies against SARS-CoV-2 receptor-binding domain, and levels of anti-SARS-CoV-2 spike IgG and neutralising antibodies. We linked participant data with national mortality, COVID-19 case, and vaccination registries. We estimated population seroprevalence and vaccine uptake, as well as unvaccinated population prior-infection prevalence. Findings: At the final round in late 2021, 82% (n = 4088) of participants completed follow-up. Estimated seroprevalence increased from 1.5% (95% CI: 1.2-2.0), to 82.3% (95% CI: 79.5-84.8) between late-2020 and late-2021. At the final round an estimated 62.4% (95% CI: 60.2-64.5) of the population were vaccinated, and of the unvaccinated population 64.5% (95% CI: 59.7-69.0) had been infected. Cumulative case ascertainment in the unvaccinated was 22.8% (95% CI: 19.1%-26.9%) and the overall infection-fatality ratio was 0.100% (95% CI: 0.088-0.124). Health workers had higher odds for being COVID-19 confirmed cases at all rounds. Males (1.72 (95% CI: 1.33-2.22)) and adults aged 20 and above (12.70 (95% CI: 8.14-20.26)) had higher odds for seroconverting by mid-2021. Among the seropositive, 87.1% (95% CI: 82.3%-90.8%) had SARS-CoV-2 neutralising antibodies by late 2021. Interpretation: Our study enabled tracking of SARS-CoV-2 serological markers in the Mongolian population over one year. We found low SARS-CoV-2 seroprevalence in 2020 and early 2021, with seropositivity increasing over a 3-month interval in 2021 due to vaccine roll out and rapid infection of most of the unvaccinated population. Despite high seroprevalence in Mongolia amongst both vaccinated and unvaccinated individuals by end-2021, the SARS-CoV-2 Omicron immune escape variant caused a substantial epidemic. Funding: World Health Organization, WHO UNITY Studies initiative, with funding by the COVID-19 Solidarity Response Fund and the German Federal Ministry of Health (BMG) COVID-19 Research and development. The Ministry of Health, Mongolia partially funded this study.

Facing the future of respiratory virus surveillance: "The mosaic surveillance framework".

It is impossible to address the many complex needs of respiratory virus surveillance with a single system. Therefore, multiple surveillance systems and complementary studies must fit together as tiles in a "mosaic" to provide a complete picture of the risk, transmission, severity, and impact of respiratory viruses of epidemic and pandemic potential. Below we present a framework (WHO Mosaic Respiratory Surveillance Framework) to assist national authorities to identify priority respiratory virus surveillance objectives and the best approaches to meet them; to develop implementation plans according to national context and resources; and to prioritize and target technical assistance and financial investments to meet most pressing needs.

Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: a systematic review and meta-regression.

BACKGROUND: The global surge in the omicron (B.1.1.529) variant has resulted in many individuals with hybrid immunity (immunity developed through a combination of SARS-CoV-2 infection and vaccination). We aimed to systematically review the magnitude and duration of the protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against infection and severe disease caused by the omicron variant. METHODS: For this systematic review and meta-regression, we searched for cohort, cross-sectional, and case-control studies in MEDLINE, Embase, Web of Science, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, the WHO COVID-19 database, and Europe PubMed Central from Jan 1, 2020, to June 1, 2022, using keywords related to SARS-CoV-2, reinfection, protective effectiveness, previous infection, presence of antibodies, and hybrid immunity. The main outcomes were the protective effectiveness against reinfection and against hospital admission or severe disease of hybrid immunity, hybrid immunity relative to previous infection alone, hybrid immunity relative to previous vaccination alone, and hybrid immunity relative to hybrid immunity with fewer vaccine doses. Risk of bias was assessed with the Risk of Bias In Non-Randomized Studies of Interventions Tool. We used log-odds random-effects meta-regression to estimate the magnitude of protection at 1-month intervals. This study was registered with PROSPERO (CRD42022318605). FINDINGS: 11 studies reporting the protective effectiveness of previous SARS-CoV-2 infection and 15 studies reporting the protective effectiveness of hybrid immunity were included. For previous infection, there were 97 estimates (27 with a moderate risk of bias and 70 with a serious risk of bias). The effectiveness of previous infection against hospital admission or severe disease was 74·6% (95% CI 63·1-83·5) at 12 months. The effectiveness of previous infection against reinfection waned to 24·7% (95% CI 16·4-35·5) at 12 months. For hybrid immunity, there were 153 estimates (78 with a moderate risk of bias and 75 with a serious risk of bias). The effectiveness of hybrid immunity against hospital admission or severe disease was 97·4% (95% CI 91·4-99·2) at 12 months with primary series vaccination and 95·3% (81·9-98·9) at 6 months with the first booster vaccination after the most recent infection or vaccination. Against reinfection, the effectiveness of hybrid immunity following primary series vaccination waned to 41·8% (95% CI 31·5-52·8) at 12 months, while the effectiveness of hybrid immunity following first booster vaccination waned to 46·5% (36·0-57·3) at 6 months. INTERPRETATION: All estimates of protection waned within months against reinfection but remained high and sustained for hospital admission or severe disease. Individuals with hybrid immunity had the highest magnitude and durability of protection, and as a result might be able to extend the period before booster vaccinations are needed compared to individuals who have never been infected. FUNDING: WHO COVID-19 Solidarity Response Fund and the Coalition for Epidemic Preparedness Innovations.

Global SARS-CoV-2 seroprevalence from January 2020 to April 2022: A systematic review and meta-analysis of standardized population-based studies.

BACKGROUND: Our understanding of the global scale of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains incomplete: Routine surveillance data underestimate infection and cannot infer on population immunity; there is a predominance of asymptomatic infections, and uneven access to diagnostics. We meta-analyzed SARS-CoV-2 seroprevalence studies, standardized to those described in the World Health Organization's Unity protocol (WHO Unity) for general population seroepidemiological studies, to estimate the extent of population infection and seropositivity to the virus 2 years into the pandemic. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis, searching MEDLINE, Embase, Web of Science, preprints, and grey literature for SARS-CoV-2 seroprevalence published between January 1, 2020 and May 20, 2022. The review protocol is registered with PROSPERO (CRD42020183634). We included general population cross-sectional and cohort studies meeting an assay quality threshold (90% sensitivity, 97% specificity; exceptions for humanitarian settings). We excluded studies with an unclear or closed population sample frame. Eligible studies-those aligned with the WHO Unity protocol-were extracted and critically appraised in duplicate, with risk of bias evaluated using a modified Joanna Briggs Institute checklist. We meta-analyzed seroprevalence by country and month, pooling to estimate regional and global seroprevalence over time; compared seroprevalence from infection to confirmed cases to estimate underascertainment; meta-analyzed differences in seroprevalence between demographic subgroups such as age and sex; and identified national factors associated with seroprevalence using meta-regression. We identified 513 full texts reporting 965 distinct seroprevalence studies (41% low- and middle-income countries [LMICs]) sampling 5,346,069 participants between January 2020 and April 2022, including 459 low/moderate risk of bias studies with national/subnational scope in further analysis. By September 2021, global SARS-CoV-2 seroprevalence from infection or vaccination was 59.2%, 95% CI [56.1% to 62.2%]. Overall seroprevalence rose steeply in 2021 due to infection in some regions (e.g., 26.6% [24.6 to 28.8] to 86.7% [84.6% to 88.5%] in Africa in December 2021) and vaccination and infection in others (e.g., 9.6% [8.3% to 11.0%] in June 2020 to 95.9% [92.6% to 97.8%] in December 2021, in European high-income countries [HICs]). After the emergence of Omicron in March 2022, infection-induced seroprevalence rose to 47.9% [41.0% to 54.9%] in Europe HIC and 33.7% [31.6% to 36.0%] in Americas HIC. In 2021 Quarter Three (July to September), median seroprevalence to cumulative incidence ratios ranged from around 2:1 in the Americas and Europe HICs to over 100:1 in Africa (LMICs). Children 0 to 9 years and adults 60+ were at lower risk of seropositivity than adults 20 to 29 (p < 0.001 and p = 0.005, respectively). In a multivariable model using prevaccination data, stringent public health and social measures were associated with lower seroprevalence (p = 0.02). The main limitations of our methodology include that some estimates were driven by certain countries or populations being overrepresented. CONCLUSIONS: In this study, we observed that global seroprevalence has risen considerably over time and with regional variation; however, over one-third of the global population are seronegative to the SARS-CoV-2 virus. Our estimates of infections based on seroprevalence far exceed reported Coronavirus Disease 2019 (COVID-19) cases. Quality and standardized seroprevalence studies are essential to inform COVID-19 response, particularly in resource-limited regions.

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

INTRODUCTION: Estimating 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. METHODS: We searched for seroprevalence studies conducted in Africa published 1 January 2020-30 December 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 seroprevalence protocol. 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. RESULTS: We identified 56 full texts or early results, reporting 153 distinct seroprevalence studies in Africa. Of these, 97 (63%) were low/moderate risk of bias studies. SARS-CoV-2 seroprevalence rose from 3.0% (95% CI 1.0% to 9.2%) in April-June 2020 to 65.1% (95% CI 56.3% to 73.0%) in July-September 2021. The ratios of seroprevalence from infection to cumulative incidence of confirmed cases was large (overall: 100:1, ranging from 18:1 to 954:1) and steady over time. Seroprevalence was highly heterogeneous both within countries-urban versus rural (lower seroprevalence for rural geographic areas), children versus adults (children aged 0-9 years had the lowest seroprevalence)-and between countries and African subregions. CONCLUSION: We report high seroprevalence in Africa suggesting greater population exposure to SARS-CoV-2 and potential protection against COVID-19 severe disease than indicated by surveillance data. As seroprevalence was heterogeneous, targeted PHSM and vaccination strategies need to be tailored to local epidemiological situations.

Transmission of SARS-CoV-2 in standardised first few X cases and household transmission investigations: A systematic review and meta-analysis.

We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for "Unity-aligned" First Few X cases (FFX) and HHTIs published 1 December 2019 to 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 Unity Studies collaborators) were retained in the systematic review; 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2% to 90% (95% prediction interval: 3%-71%; I 2 = 99.7%); I 2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.

Early epidemiological investigations: World Health Organization UNITY protocols provide a standardized and timely international investigation framework during the COVID-19 pandemic.

BACKGROUND: The declaration of Coronavirus disease 2019 (COVID-19) as a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 required rapid implementation of early investigations to inform appropriate national and global public health actions. METHODS: The suite of existing pandemic preparedness generic epidemiological early investigation protocols was rapidly adapted for COVID-19, branded the 'UNITY studies' and promoted globally for the implementation of standardized and quality studies. Ten protocols were developed investigating household (HH) transmission, the first few cases (FFX), population seroprevalence (SEROPREV), health facilities transmission (n = 2), vaccine effectiveness (n = 2), pregnancy outcomes and transmission, school transmission, and surface contamination. Implementation was supported by WHO and its partners globally, with emphasis to support building surveillance and research capacities in low- and middle-income countries (LMIC). RESULTS: WHO generic protocols were rapidly developed and published on the WHO website, 5/10 protocols within the first 3 months of the response. As of 30 June 2021, 172 investigations were implemented by 97 countries, of which 62 (64%) were LMIC. The majority of countries implemented population seroprevalence (71 countries) and first few cases/household transmission (37 countries) studies. CONCLUSION: The widespread adoption of UNITY protocols across all WHO regions indicates that they addressed subnational and national needs to support local public health decision-making to prevent and control the pandemic.

Evaluation of post-introduction COVID-19 vaccine effectiveness: Summary of interim guidance of the World Health Organization.

Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50 to 95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, emerging variants of concern, and the changing epidemiology of the pandemic, many questions still remain unanswered regarding vaccine performance. Post-introduction vaccine effectiveness evaluations can help us to understand the vaccine's effect on reducing infection and disease when used in real-world conditions. They can also address important questions that were either not studied or were incompletely studied in the trials and that will inform evolving vaccine policy, including assessment of the duration of effectiveness; effectiveness in key subpopulations, such as the very old or immunocompromised; against severe disease and death due to COVID-19; against emerging SARS-CoV-2 variants of concern; and with different vaccination schedules, such as number of doses and varying dosing intervals. WHO convened an expert panel to develop interim best practice guidance for COVID-19 vaccine effectiveness evaluations. We present a summary of the interim guidance, including discussion of different study designs, priority outcomes to evaluate, potential biases, existing surveillance platforms that can be used, and recommendations for reporting results.