First imported Cases of MPXV Clade Ib in Goma, Democratic Republic of the Congo: Implications for Global Surveillance and Transmission Dynamics.

The ongoing national mpox outbreak in the Democratic Republic of the Congo has resulted in more >30,000 suspected cases in the country from January 2023 to August 2024. While these historic case totals have been driven by primarily by zoonosis, the emergence of Clade Ib monkeypox virus (MPXV), which is connected to more sustained human-to-human transmission, has been associated with increasing public health impacts in eastern DRC. First identified in South Kivu province, Clade Ib MPXV has been identified in multiple non-endemic East African countries for the first time. In DRC, there have been concerns over broader Clade Ib expansion in the country that could further complicate containment and mitigation responses. Here, we report the first introductions of Clade Ib into North Kivu province, including within internal displacement camps, with suspected close contact transmission that includes non-intimate contacts and children. These findings demonstrate that mpox case investigations and community messaging campaigns should include considerations for non-sexual contact-mediated transmission of Clade Ib that includes children <15 years.

Global genomic surveillance of monkeypox virus.

Monkeypox virus (MPXV) is endemic in Western and Central Africa and, in May 2022, a clade IIb lineage (B.1) caused a global outbreak outside Africa, resulting in its detection in 116 countries/territories. To understand the global phylogenetics of MPXV, we analysed all available MPXV sequences, including 10,670 sequences from 65 countries collected between 1958 and 2024. Our analysis reveals high mobility of clade I viruses within Central Africa, sustained human-to-human transmission of clade IIb lineage A viruses within the Eastern Mediterranean region, and distinct mutational signatures that can distinguish sustained human-to-human from animal-to-animal transmission. Moreover, distinct clade I sequences from Sudan suggest local MPXV circulation in areas of Eastern Africa over the past four decades. Our study underscores the importance of genomic surveillance in tracking spatiotemporal dynamics of MXPV clades and the need to strengthen such surveillance, including in some parts of Eastern Africa.

Clade I mpox virus genomic diversity in the Democratic Republic of the Congo, 2018-2024: Predominance of zoonotic transmission.

Recent reports raise concerns on the changing epidemiology of mpox in the Democratic Republic of the Congo (DRC). High-quality genomes were generated for 337 patients from 14/26 provinces to document whether the increase in number of cases is due to zoonotic spillover events or viral evolution, with enrichment of APOBEC3 mutations linked to human adaptation. Our study highlights two patterns of transmission contributing to the source of human cases. All new sequences from the eastern South Kivu province (n = 17; 4.8%) corresponded to the recently described clade Ib, associated with sexual contact and sustained human-to-human transmission. By contrast, all other genomes are clade Ia, which exhibits high genetic diversity with low numbers of APOBEC3 mutations compared with clade Ib, suggesting multiple zoonotic introductions. The presence of multiple clade I variants in urban areas highlights the need for coordinated international response efforts and more studies on the transmission and the reservoir of mpox.

Co-circulation of monkeypox virus subclades Ia and Ib in Kinshasa Province, Democratic Republic of the Congo, July to August 2024.

Between January and August 2024, mpox cases have been reported in nearly all provinces of the Democratic Republic of the Congo (DRC). Monkeypox virus genome sequences were obtained from 11 mpox cases' samples, collected in July-August 2024 in several health zones of Kinshasa. Characterisation of the sequences showed subclades Ia and Ib co-circulating in the Limete health zone, while phylogenetic analyses suggested multiple introductions of the two subclades in Kinshasa. This illustrates the growing complexity of Clade I mpox outbreaks in DRC.

Adherence of SARS-CoV-2 Seroepidemiologic Studies to the ROSES-S Reporting Guideline During the COVID-19 Pandemic.

BACKGROUND: Complete reporting of seroepidemiologic studies is critical to their utility in evidence synthesis and public health decision making. The Reporting of Seroepidemiologic studies-SARS-CoV-2 (ROSES-S) guideline is a checklist that aims to improve reporting in SARS-CoV-2 seroepidemiologic studies. Adherence to the ROSES-S guideline has not yet been evaluated. OBJECTIVES: This study aims to evaluate the completeness of SARS-CoV-2 seroepidemiologic study reporting by the ROSES-S guideline during the COVID-19 pandemic, determine whether guideline publication was associated with reporting completeness, and identify study characteristics associated with reporting completeness. METHODS: A random sample from the SeroTracker living systematic review database was evaluated. For each reporting item in the guideline, the percentage of studies that were adherent was calculated, as well as median and interquartile range (IQR) adherence across all items and by item domain. Beta regression analyses were used to evaluate predictors of adherence to ROSES-S. RESULTS: One hundred and ninety-nine studies were analyzed. Median adherence was 48.1% (IQR 40.0%-55.2%) per study, with overall adherence ranging from 8.8% to 72.7%. The laboratory methods domain had the lowest median adherence (33.3% [IQR 25.0%-41.7%]). The discussion domain had the highest median adherence (75.0% [IQR 50.0%-100.0%]). Reporting adherence to ROSES-S before and after guideline publication did not significantly change. Publication source (p < 0.001), study risk of bias (p = 0.001), and sampling method (p = 0.004) were significantly associated with adherence. CONCLUSIONS: Completeness of reporting in SARS-CoV-2 seroepidemiologic studies was suboptimal. Publication of the ROSES-S guideline was not associated with changes in reporting practices. Authors should improve adherence to the ROSES-S guideline with support from stakeholders.

Informing the pandemic response: the role of the WHO's COVID-19 Weekly Epidemiological Update.

On 31 December 2019, the Municipal Health Commission of Wuhan, China, reported a cluster of atypical pneumonia cases. On 5 January 2020, the WHO publicly released a Disease Outbreak News (DON) report, providing information about the pneumonia cases, implemented response interventions, and WHO's risk assessment and advice on public health and social measures. Following 9 additional DON reports and 209 daily situation reports, on 17 August 2020, WHO published the first edition of the COVID-19 Weekly Epidemiological Update (WEU). On 1 September 2023, the 158th edition of the WEU was published on WHO's website, marking its final issue. Since then, the WEU has been replaced by comprehensive global epidemiological updates on COVID-19 released every 4 weeks. During the span of its publication, the webpage that hosts the WEU and the COVID-19 Operational Updates was accessed annually over 1.4 million times on average, with visits originating from more than 100 countries. This article provides an in-depth analysis of the WEU process, from data collection to publication, focusing on the scope, technical details, main features, underlying methods, impact and limitations. We also discuss WHO's experience in disseminating epidemiological information on the COVID-19 pandemic at the global level and provide recommendations for enhancing collaboration and information sharing to support future health emergency responses.

WHO's Investigations and Studies, Unity Studies: A global initiative creating equitable opportunities for enhanced surveillance, operational research, capacity building, and global knowledge sharing.

The World Health Organization's Unity Studies global initiative provides a generic preparedness and readiness framework for conducting detailed investigations and epidemiological studies critical for the early and ongoing assessment of emerging respiratory pathogens of pandemic potential. During the COVID-19 pandemic, the initiative produced standardized investigation protocols and supported Member States to generate robust and comparable data to inform public health decision making. The subsequent iteration of the initiative is being implemented to develop revised and new investigation protocols, implementation toolkits and work to build a sustainable global network of sites, enabling the global community to be better prepared for the next emerging respiratory pathogen with epidemic or pandemic potential.

Human mpox: global trends, molecular epidemiology and options for vaccination.

The eradication of smallpox and the cessation of vaccination have led to the growth of the susceptible human population to poxviruses. This has led to the increasing detection of zoonotic orthopoxviruses. Among those viruses, monkeypox virus (MPV) is the most commonly detected in Western and Central African regions. Since 2022, MPV is causing local transmission in newly affected countries all over the world. While the virus causing the current outbreak remains part of clade II (historically referred to as West African clade), it has a significant number of mutations as compared to other clade II sequences and is therefore referred to as clade IIb. It remains unclear whether those mutations may have caused a change in the virus phenotype. Vaccine effectiveness data show evidence of a high cross-protection of vaccines designed to prevent smallpox against mpox. These vaccines therefore represent a great opportunity to control human-to-human transmission, provided that their availability has short time-frames and that mistakes from the recent past (vaccine inequity) will not be reiterated.

Systematic review of seroprevalence of SARS-CoV-2 antibodies and appraisal of evidence, prior to the widespread introduction of vaccine programmes in the WHO European Region, January-December 2020.

OBJECTIVES: Systematic review of SARS-CoV-2 seroprevalence studies undertaken in the WHO European Region to measure pre-existing and cumulative seropositivity prior to the roll out of vaccination programmes. DESIGN: A systematic review of the literature. DATA SOURCES: We searched MEDLINE, EMBASE and the preprint servers MedRxiv and BioRxiv in the WHO 'COVID-19 Global literature on coronavirus disease' database using a predefined search strategy. Articles were supplemented with unpublished WHO-supported Unity-aligned seroprevalence studies and other studies reported directly to WHO Regional Office for Europe and European Centre for Disease Prevention and Control. ELIGIBILITY CRITERIA: Studies published before the widespread implementation of COVID-19 vaccination programmes in January 2021 among the general population and blood donors, at national and regional levels. DATA EXTRACTION AND SYNTHESIS: At least two independent researchers extracted the eligible studies; a third researcher resolved any disagreements. Study risk of bias was assessed using a quality scoring system based on sample size, sampling and testing methodologies. RESULTS: In total, 111 studies from 26 countries published or conducted between 1 January 2020 and 31 December 2020 across the WHO European Region were included. A significant heterogeneity in implementation was noted across the studies, with a paucity of studies from the east of the Region. Sixty-four (58%) studies were assessed to be of medium to high risk of bias. Overall, SARS-CoV-2 seropositivity prior to widespread community circulation was very low. National seroprevalence estimates after circulation started ranged from 0% to 51.3% (median 2.2% (IQR 0.7-5.2%); n=124), while subnational estimates ranged from 0% to 52% (median 5.8% (IQR 2.3%-12%); n=101), with the highest estimates in areas following widespread local transmission. CONCLUSIONS: The low levels of SARS-CoV-2 antibody in most populations prior to the start of vaccine programmes underlines the critical importance of targeted vaccination of priority groups at risk of severe disease, while maintaining reduced levels of transmission to minimise population morbidity and mortality.

Surveillance for variants of SARS-CoV-2 to inform risk assessments.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged, some leading to large increases in infections, hospitalizations and deaths globally. The virus's impact on public health depends on many factors, including the emergence of new viral variants and their global spread. Consequently, the early detection and surveillance of variants and characterization of their clinical effects are vital for assessing their health risk. The unprecedented capacity for viral genomic sequencing and data sharing built globally during the pandemic has enabled new variants to be rapidly detected and assessed. This article describes the main variants circulating globally between January 2020 and June 2023, the genetic features driving variant evolution, and the epidemiological impact of these variants across countries and regions. Second, we report how integrating genetic variant surveillance with epidemiological data and event-based surveillance, through a network of World Health Organization partners, supported risk assessment and helped provide guidance on pandemic responses. In addition, given the evolutionary characteristics of circulating variants and the immune status of populations, we propose future directions for the sustainable genomic surveillance of SARS-CoV-2 variants, both nationally and internationally: (i) optimizing variant surveillance by including environmental monitoring; (ii) coordinating laboratory assessment of variant evolution and phenotype; (iii) linking data on circulating variants with clinical data; and (iv) expanding genomic surveillance to additional pathogens. Experience during the COVID-19 pandemic has shown that genomic surveillance of pathogens can provide essential, timely and evidence-based information for public health decision-making.

Depuis le début de la pandémie de coronavirus survenue en 2019 (COVID-19), de nombreux variants du coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2) sont apparus, certains entraînant une forte augmentation du nombre d'infections, d'hospitalisations et de décès dans le monde. L'impact du virus sur la santé publique dépend de nombreux facteurs, notamment l'émergence de nouveaux variants viraux et leur propagation à l'échelle mondiale. Par conséquent, la détection précoce et la surveillance des variants ainsi que la caractérisation de leurs effets cliniques sont essentielles pour évaluer leur risque pour la santé. La capacité sans précédent de séquençage du génome viral et de partage des données, capacité mise en place à l'échelle mondiale pendant la pandémie, a permis de détecter et d'évaluer rapidement de nouveaux variants. Le présent article décrit les principaux variants circulant dans le monde entre janvier 2020 et juin 2023, les caractéristiques génétiques à l'origine de leur évolution et leur impact épidémiologique dans les différents pays et régions. Ensuite, nous expliquerons comment l'intégration de la surveillance des variants génétiques aux données épidémiologiques et à la surveillance fondée sur les événements, par l'intermédiaire d'un réseau de partenaires de l'Organisation mondiale de la santé, a permis de faciliter l'évaluation des risques et de fournir des orientations sur les mesures à prendre en période de pandémie. En outre, compte tenu des caractéristiques évolutives des variants en circulation et de l'état immunitaire des populations, nous proposons des orientations futures pour une surveillance génomique durable des variants du SARS-CoV-2, au niveau tant national qu'international: (i) optimiser la surveillance des variants en incluant le suivi environnemental; (ii) coordonner l'évaluation en laboratoire de l'évolution des variants et du phénotype; (iii) établir un lien entre les données sur les variants en circulation et les données cliniques; et (iv) étendre la surveillance génomique à d'autres agents pathogènes. L'expérience de la pandémie de COVID-19 a mis en évidence que la surveillance génomique des agents pathogènes peut fournir en temps utile des informations essentielles fondées sur des preuves en vue de la prise de décisions en matière de santé publique.

Desde el inicio de la pandemia de la enfermedad por coronavirus de 2019 (COVID-19), han aparecido numerosas variantes del coronavirus de tipo 2 causante del síndrome respiratorio agudo severo (SRAS-CoV-2), algunas de las que han provocado un gran aumento de las infecciones, hospitalizaciones y muertes en todo el mundo. El impacto del virus en la salud pública depende de muchos factores, entre ellos la aparición de nuevas variantes víricas y su propagación mundial. En consecuencia, la detección y vigilancia tempranas de las variantes y la caracterización de sus efectos clínicos son vitales para evaluar su riesgo sanitario. La capacidad sin precedentes de secuenciación genómica viral y de intercambio de datos creada a nivel mundial durante la pandemia ha permitido detectar y evaluar rápidamente variantes nuevas. En este artículo se describen las principales variantes que circulan a nivel mundial entre enero de 2020 y junio de 2023, la característica genética que impulsa la evolución de las variantes y el impacto epidemiológico de estas variantes en los diferentes países y regiones. En segundo lugar, se informa de cómo la integración de la vigilancia de variantes genéticas con los datos epidemiológicos y la vigilancia basada en eventos, a través de una red de asociados de la Organización Mundial de la Salud, apoyó la evaluación de riesgos y ayudó a proporcionar orientación sobre las respuestas a la pandemia. Además, dadas las características evolutivas de las variantes circulantes y el estado inmunitario de las poblaciones, se proponen orientaciones futuras para la vigilancia genómica sostenible de las variantes del SRAS-CoV-2, tanto a nivel nacional como internacional: (i) optimizar la vigilancia de las variantes mediante la inclusión de la monitorización ambiental; (ii) coordinar la evaluación de laboratorio de la evolución y el fenotipo de las variantes; (iii) vincular los datos sobre las variantes circulantes con los datos clínicos; y (iv) ampliar la vigilancia genómica a patógenos adicionales. La experiencia durante la pandemia de la COVID-19 ha demostrado que la vigilancia genómica de patógenos puede proporcionar información esencial, oportuna y basada en evidencias para la toma de decisiones en materia de salud pública.

Evolution of seroprevalence to SARS-CoV-2 in blood donors in Sarajevo Canton, Federation of Bosnia and Herzegovina: Cross-sectional and longitudinal studies.

Background: Sarajevo Canton in the Federation of Bosnia and Herzegovina has recorded several waves of high SARS-CoV-2 transmission and has struggled to reach adequate vaccination coverage. We describe the evolution of infection- and vaccine-induced SARS-CoV-2 antibody response and persistence. Methods: We conducted repeated cross-sectional analyses of blood donors aged 18-65 years in Sarajevo Canton in November-December 2020 and 2021. We analyzed serum samples for anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies. To assess immune durability, we conducted longitudinal analyses of seropositive participants at 6 and 12 months. Results: One thousand fifteen participants were included in Phase 1 (November-December 2020) and 1152 in Phase 2 (November-December 2021). Seroprevalence increased significantly from 19.2% (95% CI: 17.2%-21.4%) in Phase 1 to 91.6% (95% CI: 89.8%-93.1%) in Phase 2. Anti-S IgG titers were significantly higher among vaccinated (58.5%) than unvaccinated infected participants across vaccine products (p < 0.001), though highest among those who received an mRNA vaccine. At 6 months, 78/82 (95.1%) participants maintained anti-spike seropositivity; at 12 months, 58/58 (100.0%) participants were seropositive, and 33 (56.9%) had completed the primary vaccine series within 6 months. Among 11 unvaccinated participants who were not re-infected at 12 months, anti-S IgG declined from median 770.1 (IQR 615.0-1321.7) to 290.8 (IQR 175.7-400.3). Anti-N IgG antibodies waned earlier, from 35.4% seropositive at 6 months to 24.1% at 12 months. Conclusions: SARS-CoV-2 seroprevalence increased significantly over 12 months from end of 2020 to end of 2021. Although individuals with previous infection may have residual protection, COVID-19 vaccination is vital to strengthening population immunity.

Short communication-Lessons learnt during the implementation of Unity-aligned SARS-CoV-2 seroprevalence studies in Africa.

The WHO Unity Studies initiative engaged low- and middle-income countries in the implementation of standardised SARS-CoV-2 sero-epidemiological investigation protocols and timely sharing of comparable results for evidence-based action. To gain a deeper understanding of the methodological challenges faced when conducting seroprevalence studies in the African region, we conducted unstructured interviews with key study teams in five countries. We discuss the challenges identified: participant recruitment and retention, sampling, sample and data management, data analysis and presentation. Potential solutions to aid future implementation include preparedness actions such as the development of new tools, robust planning and practice.

Towards the development of a SARS-CoV-2 variant risk assessment tool: expert consultation on the assessment of scientific evidence on emerging variants.

A systematic approach is required for the development of an evidence-based risk assessment tool to robustly estimate the risks and implications of SARS-CoV-2 variants. We conducted a survey among experts involved in technical advisory roles for WHO to capture their assessment of the robustness of different study types that provide evidence for potential changes in transmissibility, antigenicity, virulence, treatability, and detectability of SARS-CoV-2 variants. The views of 62 experts indicated that studies could be grouped on the basis of robustness and reliability for the different risk indicators mentioned. Several study types that experts scored as providing reliable evidence and that can be performed in a timely manner were identified. Although experts from different technical areas had varying responses, there was agreement on the highest and lowest scoring study types. These findings can help to prioritise, harmonise, and optimise study designs for the further development of a systematic, evidence-based, SARS-CoV-2 variant risk assessment tool.

Comprehensive, Comparative Evaluation of 35 Manual SARS-CoV-2 Serological Assays.

The onset of the coronavirus disease 2019 (COVID-19) pandemic resulted in hundreds of in vitro diagnostic devices (IVDs) coming to market, facilitated by regulatory authorities allowing "emergency use" without a comprehensive evaluation of performance. The World Health Organization (WHO) released target product profiles (TPPs) specifying acceptable performance characteristics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assay devices. We evaluated 26 rapid diagnostic tests and 9 enzyme immunoassays (EIAs) for anti-SARS-CoV-2, suitable for use in low- and middle-income countries (LMICs), against these TPPs and other performance characteristics. The sensitivity and specificity ranged from 60.1 to 100% and 56.0 to 100%, respectively. Five of 35 test kits reported no false reactivity for 55 samples with potentially cross-reacting substances. Six test kits reported no false reactivity for 35 samples containing interfering substances, and only one test reported no false reactivity with samples positive for other coronaviruses (not SARS-CoV-2). This study demonstrates that a comprehensive evaluation of the performance of test kits against defined specifications is essential for the selection of test kits, especially in a pandemic setting. IMPORTANCE The markets have been flooded with hundreds of SARS-CoV-2 serology tests, and although there are many published reports on their performance, comparative reports are far fewer and tend to be limited to only a few tests. In this report, we comparatively assessed 35 rapid diagnostic tests or microtiter plate enzyme immunoassays (EIAs) using a large set of samples from individuals with a history of mild to moderate COVID-19, commensurate with the target population for serosurveillance, which included serum samples from individuals previously infected, at undetermined time periods, with other seasonal human coronaviruses, Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-1. The significant heterogeneity in their performances, with only a few tests meeting WHO target product profile performance requirements, highlights the importance of independent comparative assessments to inform the use and procurement of these tests for both diagnostics and epidemiological investigations.

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.

Viral clade is associated with severity of symptomatic genotype 3 hepatitis E virus infections in Belgium, 2010-2018.

BACKGROUND & AIMS: HEV genotype (gt) 3 infections are prevalent in high-income countries and display a wide spectrum of clinical presentations. Host - but not viral - factors are reported to be associated with worse clinical outcomes. METHODS: Demographic, clinical, and biochemical data laboratory-confirmed HEV infections (by PCR and/or a combination of IgM and IgG serology) at the Belgian National Reference Centre between January 2010 and June 2018 were collected using standardised case report forms. Genotyping was based on HEV open reading frame 2 sequences. Serum CXCL10 levels were measured by a magnetic bead-based assay. H&E staining was performed on liver biopsies. RESULTS: A total of 274 HEV-infected individuals were included. Subtype assignment was possible for 179/218 viraemic cases, confirming gt3 as dominant with an almost equal representation of clades abchijklm and efg. An increased hospitalisation rate and higher peak serum levels of alanine aminotransferase, bilirubin, and alkaline phosphatase were found in clade efg-infected individuals in univariate analyses. In multivariable analyses, clade efg infections remained more strongly associated with severe disease presentation than any of the previously identified host risk factors, being associated with a 2.1-fold higher risk of hospitalisation (95% CI 1.1-4.4, p = 0.034) and a 68.2% higher peak of bilirubin levels (95% CI 13.3-149.9, p = 0.010), independently of other factors included in the model. In addition, acute clade efg infections were characterised by higher serum CXCL10 levels (p = 0.0005) and a more pronounced liver necro-inflammatory activity (p = 0.022). CONCLUSIONS: In symptomatic HEV gt3 infections, clade efg is associated with a more severe disease presentation, higher serum CXCL10 levels, and liver necro-inflammatory activity, irrespective of known host risk factors. CLINICAL TRIAL REGISTRATION: The protocol was submitted to clinicaltrials.gov (NCT04670419). IMPACT AND IMPLICATIONS: HEV genotype (gt) 3 infections display a wide spectrum of clinical presentations currently ascribed to host factors. Here we examined the role of viral factors on liver disease outcomes by combining viral phylogeny with clinical, biochemical, cytokine, and histological data from 274 Belgian adults infected with HEV presenting between 2010 and 2018. HEV gt 3 clade efg infections were associated with a more severe disease presentation, higher serum CXCL10 levels and liver necro-inflammatory activity, irrespective of known host risk factors. HEV gt3 clade-dependent clinical outcomes call for broad HEV gt3 subtyping in clinical practice and research to help identify those at higher risk for worse outcomes and to further unravel underlying virus-host interactions.

Serology Assays Used in SARS-CoV-2 Seroprevalence Surveys Worldwide: A Systematic Review and Meta-Analysis of Assay Features, Testing Algorithms, and Performance.

Background: Many serological assays to detect SARS-CoV-2 antibodies were developed during the COVID-19 pandemic. Differences in the detection mechanism of SARS-CoV-2 serological assays limited the comparability of seroprevalence estimates for populations being tested. Methods: We conducted a systematic review and meta-analysis of serological assays used in SARS-CoV-2 population seroprevalence surveys, searching for published articles, preprints, institutional sources, and grey literature between 1 January 2020, and 19 November 2021. We described features of all identified assays and mapped performance metrics by the manufacturers, third-party head-to-head, and independent group evaluations. We compared the reported assay performance by evaluation source with a mixed-effect beta regression model. A simulation was run to quantify how biased assay performance affects population seroprevalence estimates with test adjustment. Results: Among 1807 included serosurveys, 192 distinctive commercial assays and 380 self-developed assays were identified. According to manufacturers, 28.6% of all commercial assays met WHO criteria for emergency use (sensitivity [Sn.] >= 90.0%, specificity [Sp.] >= 97.0%). However, manufacturers overstated the absolute values of Sn. of commercial assays by 1.0% [0.1, 1.4%] and 3.3% [2.7, 3.4%], and Sp. by 0.9% [0.9, 0.9%] and 0.2% [−0.1, 0.4%] compared to third-party and independent evaluations, respectively. Reported performance data was not sufficient to support a similar analysis for self-developed assays. Simulations indicate that inaccurate Sn. and Sp. can bias seroprevalence estimates adjusted for assay performance; the error level changes with the background seroprevalence. Conclusions: The Sn. and Sp. of the serological assay are not fixed properties, but varying features depending on the testing population. To achieve precise population estimates and to ensure the comparability of seroprevalence, serosurveys should select assays with high performance validated not only by their manufacturers and adjust seroprevalence estimates based on assured performance data. More investigation should be directed to consolidating the performance of self-developed assays.