Baseline Seroprevalence Research Articles

Hepatitis C Virus Seroprevalence, Incidence, and Screening Patterns in Ontario Preexposure Prophylaxis Users.

Hepatitis C virus (HCV) has emerged as a sexually transmitted infection in gay, bisexual, and other men who have sex with men (GBM). We estimated the seroprevalence and incidence of HCV infection and examined patterns of HCV testing among GBM using human immunodeficiency virus preexposure prophylaxis (PrEP) in Ontario, Canada. We analyzed data from the Ontario PrEP Cohort Study (ON-PrEP), a prospective cohort of PrEP users from 10 Ontario clinics. Participants completed an online questionnaire and study staff collected clinical information into a study database biannually for 2 years. We estimated the baseline seroprevalence and incidence of HCV infection and examined patterns of HCV testing during follow-up. We further explored differences in sociodemographic/clinical variables between those with and without prevalent/incident HCV infection through bivariate analysis. Among 557 eligible PrEP users, 382 (68.6%) underwent baseline HCV antibody testing, of whom 5 tested HCV seropositive, giving a seroprevalence of 1.3% (95% confidence interval [CI], .43%-3.03%). Only 245 (43.9%) participants underwent HCV antibody testing after baseline, and median time to participants' first follow-up test was 245 days. During follow-up, 2 participants tested newly HCV seropositive, giving an incidence of 0.47/100 person-years (95% CI, .06-1.69) over 428.9 years of follow-up. Participants with prevalent/incident HCV infection during the study appeared more likely to report giving money, drugs, gifts, or services for sex in the 3 months preceding enrollment compared to those who never tested HCV seropositive (P = .02). HCV seroprevalence and incidence were low but not negligible among Ontario PrEP users. HCV antibody and RNA testing were suboptimal.

Seroprevalence of immunity to hepatitis A and hepatitis B among gay, bisexual and other men who have sex with men (GBMSM) attending sexual health clinics in London and Leeds, England, 2017–2018

ObjectivesAlthough hepatitis A virus (HAV) and hepatitis B virus (HBV) immunisation is recommended in the UK for gay, bisexual and other men who have sex with men (GBMSM), data on...

Exploring Natural Immune Responses to Shigella Exposure Using Multiplex Bead Assays on Dried Blood Spots in High-Burden Countries: Protocol From a Multisite Diarrhea Surveillance Study.

Molecular diagnostics on human fecal samples have identified a larger burden of shigellosis than previously appreciated by culture. Evidence of fold changes in immunoglobulin G (IgG) to conserved and type-specific Shigella antigens could be used to validate the molecular assignment of type-specific Shigella as the etiology of acute diarrhea and support polymerase chain reaction (PCR)-based microbiologic end points for vaccine trials. We will test dried blood spots collected at enrollment and 4 weeks later using bead-based immunoassays for IgG to invasion plasmid antigen B and type-specific lipopolysaccharide O-antigen for Shigella flexneri 1b, 2a, 3a, and 6 and Shigella sonnei in Shigella-positive cases and age-, site-, and season-matched test-negative controls from all sites in the Enterics for Global Health (EFGH) Shigella surveillance study. Fold antibody responses will be compared between culture-positive, culture-negative but PCR-attributable, and PCR-positive but not attributable cases and test-negative controls. Age- and site-specific seroprevalence distributions will be identified, and the association between baseline antibodies and Shigella attribution will be estimated. The integration of these assays into the EFGH study will help support PCR-based attribution of acute diarrhea to type-specific Shigella, describe the baseline seroprevalence of conserved and type-specific Shigella antibodies, and support correlates of protection for immunity to Shigella diarrhea. These insights can help support the development and evaluation of Shigella vaccine candidates.

Investigating SARS-CoV-2 Incidence and Morbidity in Ponce, Puerto Rico: Protocol and Baseline Results From a Community Cohort Study.

A better understanding of SARS-CoV-2 infection risk among Hispanic and Latino populations and in low-resource settings in the United States is needed to inform control efforts and strategies to improve health equity. Puerto Rico has a high poverty rate and other population characteristics associated with increased vulnerability to COVID-19, and there are limited data to date to determine community incidence. This study describes the protocol and baseline seroprevalence of SARS-CoV-2 in a prospective community-based cohort study (COPA COVID-19 [COCOVID] study) to investigate SARS-CoV-2 infection incidence and morbidity in Ponce, Puerto Rico. In June 2020, we implemented the COCOVID study within the Communities Organized to Prevent Arboviruses project platform among residents of 15 communities in Ponce, Puerto Rico, aged 1 year or older. Weekly, participants answered questionnaires on acute symptoms and preventive behaviors and provided anterior nasal swab samples for SARS-CoV-2 polymerase chain reaction testing; additional anterior nasal swabs were collected for expedited polymerase chain reaction testing from participants that reported 1 or more COVID-19-like symptoms. At enrollment and every 6 months during follow-up, participants answered more comprehensive questionnaires and provided venous blood samples for multiantigen SARS-CoV-2 immunoglobulin G antibody testing (an indicator of seroprevalence). Weekly follow-up activities concluded in April 2022 and 6-month follow-up visits concluded in August 2022. Primary study outcome measures include SARS-CoV-2 infection incidence and seroprevalence, relative risk of SARS-CoV-2 infection by participant characteristics, SARS-CoV-2 household attack rate, and COVID-19 illness characteristics and outcomes. In this study, we describe the characteristics of COCOVID participants overall and by SARS-CoV-2 seroprevalence status at baseline. We enrolled a total of 1030 participants from 388 households. Relative to the general populations of Ponce and Puerto Rico, our cohort overrepresented middle-income households, employed and middle-aged adults, and older children (P<.001). Almost all participants (1021/1025, 99.61%) identified as Latino/a, 17.07% (175/1025) had annual household incomes less than US $10,000, and 45.66% (463/1014) reported 1 or more chronic medical conditions. Baseline SARS-CoV-2 seroprevalence was low (16/1030, 1.55%) overall and increased significantly with later study enrollment time (P=.003). The COCOVID study will provide a valuable opportunity to better estimate the burden of SARS-CoV-2 and associated risk factors in a primarily Hispanic or Latino population, assess the limitations of surveillance, and inform mitigation measures in Puerto Rico and other similar populations. RR1-10.2196/53837.

Baseline Seroprevalence of SARS-CoV-2 Specific Antibodies in Hot Spot Areas of Great Tunis, up to 3 Months Post Disease Onset in Tunisia.

The extent of the SARS-CoV-2 circulation and the COVID-19 epidemic in Tunisia three months after virus circulation was unknown. The aim of this study was to determine the extent of SARS-CoV-2 infection among household contacts of confirmed COVID-19 cases living in Hot spot areas of Great Tunis, Tunisia by estimating the seroprevalence of antibodies anti SARS-CoV-2 and to identify factors associated to seroprevalence at the first stage of the pandemic in order to guide decision making and to constitute a baseline for further longitudinal analysis of protective immunity to SARS-CoV-2. The National Observatory of New and Emerging Diseases (ONMNE), Ministry of Health Tunisia (MoH), with the support of the Office of the World Health Organization Representative in Tunisia and the WHO Regional Office for the Eastern Mediterranean (EMRO)), conducted a household cross-sectional survey on April 2020 in Great Tunis (Tunis, Ariana, Manouba and Ben Arous). The study was based on the WHO seroepidemiological investigation protocol for SARS-CoV-2 infection. SARS-CoV-2 specific antibodies (IgG and IgM) were qualitatively detected using a lateral immunoassay that detect SARS-CoV-2 nucleocapsid protein and administered by the interviewers. The included subjects were confirmed COVID-19 cases and their households contacts resided in hot spot areas (cumulative incidence rate ≥ 10 cases/100,000 inhabitants) of Great Tunis. Results: In total, 1165 subjects were enrolled: 116 confirmed COVID-19 cases (43 active cases and 73 convalescents cases) and 1049 household contacts resided in 291 households. The median age of participants was 39.0 with 31 years' interquartile range (Min = 8 months; Max = 96 years). The sex ratio (M/F) was 0.98. Twenty-nine per cent of participants resided in Tunis. The global crude seroprevalence among household contacts was 2.5% (26/1049); 95% CI 1.6-3.6%, 4.8%; 95% CI 2.3-8.7% in Ariana governorate and 0.3%; 95% CI 0.01%-1.8% in Manouba governorate. In multivariate analysis, the associated factors independently related to seroprevalence were age ≥25 years (aOR = 5.1; 95% CI 1.2-22.0), history of travel outside Tunisia since January 2020 (aOR = 4.6; 95% CI 1.7-12.9), symptomatic illness in the previous four months (aOR = 3.5; 95% CI 1.4-9.0) and governorate of residence (p = 0.02). The low seroprevalence estimated among household contacts in Great Tunis reflect the effect of public health measures early taken (national lockdown, borders closed, remote work), the respect of non-pharmaceutical interventions and the efficacy of COVID-19 contact-tracing and case management at the first stage of the pandemic in Tunisia.

Pre-Omicron seroprevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies among a cohort of children and teenagers in Montréal, Canada

To use serological testing to assess the pre-Omicron seroprevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies in children and adolescents in Montreal, Canada. This analysis is from a prospective cohort study of children aged 2 to 17 years (at baseline) that included blood spots (DBS) for antibody detection. The serostatus of participants was determined by enzyme-linked immunosorbent assays (ELISAs) using the receptor-binding domain (RBD) from the spike protein and the nucleocapsid protein (N) as antigens. We estimated seroprevalence, seroconversion rates, and the likelihood of seroreversion at six months and one year. The baseline (October 2020 to April 2021) seroprevalence was 5.8% (95% CI 4.8-7.1), which increased to 10.5% (May to September 2021) and 11.0% (November 2021 to March 2022) for the respective follow-ups (95% CI 8.6-12.7; 95% CI 8.8-13.5). The crude rate of seroconversion over the study period was 12.8 per 100 person-years (95% CI 11.0-14.7). Adjusted hazard rates of seroconversion by child characteristics showed higher rates in children who were female, whose parent identified as a racial or ethnic minority, and in households with incomes in the lowest tercile of our study population. The likelihood of remaining seropositive at six months was 68% (95% CI 60%-77%) and dropped to 42% (95% CI 32%-56%) at one year. Serological studies continue to provide valuable contributions for infection prevalence estimates and help us better understand the dynamics of antibody levels following infection.

Nigeria healthcare worker SARS-CoV-2 serology study: Results from a prospective, longitudinal cohort.

Healthcare workers, both globally and in Nigeria, have an increased risk for SARS-CoV-2 infection compared with the general population due to higher risk contacts, including occupational exposures. In addition, primary healthcare workers represent an important group for estimating prior infection to SARS-CoV-2 because they work at the first point-of-contact for most patients yet have not been included in prior COVID-19 seroepidemiology research in Nigeria. We sought to evaluate baseline seroprevalence, rates of seroconversion (IgG- to IgG+) and seroreversion (IgG+ to IgG-), change in IgG concentration at 3- and 6-month follow-up, and factors associated with seropositivity. From June 2020 to December 2020, we conducted a longitudinal seroepidemiology study among frontline health care workers in Nigeria using a validated dried blood spot assay. Among 525 participants, mean (SD) age was 39.1 (9.7) years, 61.0% were female, and 45.1% were community health workers. The six-month follow-up rate was 93.5%. Seropositivity rates increased from 31% (95% CI: 27%, 35%) at baseline to 45% (95% CI: 40%, 49%) at 3-month follow-up, and 70% (95% CI: 66%, 74%) at 6-month follow-up. There was a corresponding increase in IgG levels from baseline (median = 0.18 ug/mL) to 3-month (median = 0.35 ug/mL) and 6-month follow-up (median = 0.59 ug/mL, Ptrend < .0001). A minority of participants reported symptoms from February 2020 until baseline (12.2%) or during 3-month (6.6%) or 6-month (7.5%) follow-up. only 1 participant was hospitalized. This study demonstrated high baseline, 3-month and 6-month follow-up prevalence of IgG antibodies to SARS-CoV-2 during the first two waves of the COVID-19 pandemic in Nigeria among a cohort of unvaccinated frontline healthcare workers, including primary healthcare workers despite low symptomatology. These results may have implications in state- and national-level disease pandemic modeling. Trial registration: NCT04158154.

Seroepidemiological Study of Dengue Virus Infection Suspected Cases in Burkina Faso

Dengue fever is a mosquito-borne disease caused by four related but antigenically distinct dengue viruses. In the last half-century, the prevalence of dengue fever has increased dramatically (up to 30%) worldwide, especially in Sub-Saharan Africa. In Burkina Faso, the last dengue epidemic occurred in 2016, and the epidemiological situation is still poorly documented at the national level. Therefore, the present study aimed to conduct a sentinel seroepidemiology of suspected dengue virus infections from 2017 to 2020 at Charles de Gaulle University Pediatric Hospital Center of Ouagadougou. This investigation was designed to be a descriptive and analytical study. Patients with suspected cases of dengue fever were recruited from January 2017 to December 2020 during general medicine consultation and referred to Charles de Gaulle University Pediatric Hospital Center of Ouagadougou for the serological diagnosis of dengue. Venous blood was collected in dry or EDTA tubes and tested for DENV NS1 antigen, anti-dengue IgM, and anti-dengue IgG using SD Bioline Dengue Duo Rapid Detection Kit (Standard Diagnostic Inc., Korea). A total of 3400 blood samples from clinically suspected dengue cases were analyzed, of which 1784 (52.5%) were males, and 1616 (47.5%) were females. Among the 3400 patients included in the study, 661 (19.4%) were tested at least positive for NS1 antigen, anti-dengue IgM or anti-IgG. Among them, individuals positive for IgG suggesting past dengue virus infection were found in more than a third of 262 (7.7%) of the cases. Approximately, 80.0% (2705/3400) dengue suspected cases and 85.5% (341/399) early or primary dengue infections were recorded in the last four months of the study (September to December 2020), with a peak in mid-October and mid-November. There was no statistically significant difference in seroprevalence between males and females (p = 0.7), but an increasing seropositivity trend with age, from 11.6% for the patient under 5 years group to 39.7% for 30 years and over age group were noted. This study puts in evidence a considerable level of transmission of dengue viruses in Burkina Faso and provides baseline seroprevalence data. The recurrent outbreaks of dengue infection in multiple geographical areas need comprehensive surveillance and a diagnostic system to identify the actual burden and pinpoint the risk factors. A larger study is, therefore, needed to determine the actual prevalence of dengue in Burkina Faso and map the serotypes.

The cost-effectiveness of maternal and neonatal screening for congenital cytomegalovirus infection in Japan.

Congenital cytomegalovirus infection is the most common congenital infection.Using a decision tree model, cost-effectiveness of maternal screening with subsequent prenatal valacyclovir treatment and newborn screening with neonatal valganciclovir treatment was evaluated. The incremental cost-effectiveness ratio (ICER) was calculated for (1) universal maternal antibody screening with prenatal valacyclovir treatment compared to targeted newborn screening, and (2) universal newborn screening with postnatal valganciclovir treatment compared to targeted newborn screening. We performed a one-way sensitivity analysis.Compared to targeted newborn screening, the ICERs for universal newborn screening and maternal screening were 2 966 296 Japanese Yen (JPY) (21 188 USD) and 1 026 984 JPY (7336 USD), respectively. In all scenarios in the one-way sensitivity analysis, the ICERs of the maternal screening and the universal newborn screening strategies were less than three gross domestic product per capita compared with the targeted newborn screening strategy.Both maternal and universal newborn screening strategies may be cost-effective than a targeted newborn screening program. The potential utility of the maternal screening with valacyclovir treatment strategy, while potentially cost effective in regions with lower baseline seroprevalence rates, requires further study as the modeling was based on limited evidence.

Comparable diagnostic accuracy of SARS-CoV-2 Spike RBD and N-specific IgG tests to determine pre-vaccination nation-wide baseline seroprevalence in Mexico

A major challenge for developing countries during the COVID-19 pandemic is affordable and adequate monitoring of disease progression and population exposure as the primary source relevant epidemiological indicators. Serology testing enables assessing population exposure and to guide vaccination strategies but requires rigorous accuracy validation before population-wide implementation. We adapted a two-step ELISA protocol as a single-step protocol for detection of IgG against the Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein and compared its diagnostic accuracy with a commercial immunoassay anti-nucleoprotein IgG. Both methods yielded adequate and comparable diagnostic accuracy after 3 weeks post-symptom onset and were implemented in a nation-wide population based serological survey during August–November 2020. Anti-RBD National seroprevalence was 23.6%, 1.3% lower, but not significantly, than for anti-N. Double positive seroprevalence was 19.7%. Anti-N single-positive seroprevalence was 3.72% and anti-RBD single-positive seroprevalence was 1.98%. Discrepancies in the positivity to either single marker may be due to different kinetics of each antibody marker as well as the heterogeneity of the sampling time in regards to local epidemic waves. Baseline single positivity prevalence will be useful to assess the serological impact of vaccination and natural infection in further serosurveillance efforts.

Risk of COVID-19 re-infection and its predictors (CORES): protocol for a community-based longitudinal cohort study in Vellore, India

IntroductionThe incidence of SARS-CoV-2 re-infection has not been widely evaluated in low-income and middle-income countries. Understanding immune responses elicited by SARS-CoV-2 natural infection and factors that lead to re-infection in...

English

Brucellosis is endemic in pastoral settings of Tanzania with significant socio-economic implications. However, comprehensive studies to establish its impacts had not been elucidated. A longitudinal study was conducted in order to elucidate the dynamics and its impact on production and reproduction. Initially, 464 animals were enrolled with baseline seroprevalence in each herd. Animals were bled every three months to determine the incidence rate, impacts and trends in sero-status. In addition, individual animal reproductive information was collected. Milk yield was measured indirectly by estimating the calves&rsquo; growth rate. Data were analysed using Epi Info 7.0 software where descriptive analyses were used to establish proportions, associations and relationships. Wilcoxon test was used to establish the growth rate differences. Forty-seven new c-ELISA seropositive animals were identified over the period of three months representing an incidence rate of 0.811 cases per animal-year at risk. Households with a high seroprevalence during baseline screening were observed to have high infection rate in the subsequent visit. There was no statistical association between new seropositive cases and seasons (P&gt;0.05). Furthermore, positive to negative seroconversion was observed. Of the 94 females that were expected to parturate, 15% aborted with 29% of these being seropositive. Retained placenta was observed in 4.3% of the domestic ruminants. Of the 79 calves that were screened, 21.5% were seropositive with majority born from seropositive dams. Calves born from seropositive dams were 27 times more likely to be seropositive. Growth rate was not different (p&gt;0.05) between calves suckling from seropositive and seronegative dams. Key words: Brucellosis impacts, incidence rate, seropositivity.

SARS CoV-2 seroprevalence and diagnostic accuracy during a COVID-19 outbreak in a major penitentiary complex in Brazil, June to July 2020.

This study aims to estimate the overall SARS-CoV-2 seroprevalence and evaluate the accuracy of an antibody rapid test compared to a reference serological assay during a COVID-19 outbreak in a prison complex housing over 13,000 prisoners in Brasília. The authors obtained a randomized, stratified representative sample of each prison unit and conducted a repeated serosurvey among prisoners between June and July 2020, using a lateral-flow immunochromatographic assay (LFIA). Samples were also retested using a chemiluminescence enzyme immunoassay (CLIA) to compare SARS-CoV-2 seroprevalence and 21-days incidence, as well as to estimate the overall infection fatality rate (IFR) and determine the diagnostic accuracy of the LFIA test. This study identified 485 eligible individuals and enrolled 460 participants. Baseline and 21-days follow-up seroprevalence were estimated at 52.0% (95% CI 44.9-59.0) and 56.7% (95% CI 48.2-65.3) with LFIA; and 80.7% (95% CI 74.1-87.3) and 81.1% (95% CI 74.4-87.8) with CLIA, with an overall IFR of 0.02%. There were 78.2% (95% CI 66.7-89.7) symptomatic individuals among the positive cases. Sensitivity and specificity of LFIA were estimated at 43.4% and 83.3% for IgM; 46.5% and 91.5% for IgG; and 59.1% and 77.3% for combined tests. The authors found high seroprevalence of anti-SARS-CoV-2 antibodies within the prison complex. The occurrence of asymptomatic infection highlights the importance of periodic mass testing in addition to case-finding of symptomatic individuals; however, the field performance of LFIA tests should be validated. This study recommends that vaccination strategies consider the inclusion of prisoners and prison staff in priority groups.

Seroprevalence of SARS-CoV-2 in a Large Cohort of Italian Police Officers.

Certain professional categories are at a high occupational exposure to COVID-19. The aim of this survey was to quantify the seroprevalence of SARS-CoV-2 among police officers in Italy and identify its correlates. In this cross-sectional study, a nationally representative sample of State police employees was tested for IgG and IgM before the start of the National vaccination campaign. A total of 10,535 subjects (approximately 10% of the total workforce) participated in the study. The overall seroprevalence was 4.8% (95% CI: 4.4–5.3%). However, seropositivity was unevenly distributed across the country with a clear (p < 0.001) North–South gradient. In particular, the seroprevalence was 5.6 times higher in northern regions than in southern regions (9.0% vs. 1.6%). Most (71.2%) seropositive subjects reported having no recent symptoms potentially attributable to SARS-CoV-2 infection. Previous dysosmia, dysgeusia, and influenza-like illness symptoms were positive predictors of being seropositive. However, the prognostic value of dysosmia depended (p < 0.05) on both sex and prior influenza-like illness. The baseline seroprevalence of SARS-CoV-2 in police employees is considerable. A significant risk of occupational exposure, frequent asymptomatic cases and the progressive waning of neutralizing antibodies suggest that the police workers should be considered among the job categories prioritized for the booster COVID-19 vaccine dose.

Infection with severe fever with thrombocytopenia virus in healthy population: a cohort study in a high endemic region, China

BackgroundSevere fever with thrombocytopenia (SFTS) caused by SFTS virus (SFTSV) was a tick-borne hemorrhagic fever that posed significant threat to human health in Eastern Asia. The study was designed to measure the seroprevalence of SFTSV antibody in healthy population residing in a high endemic region.MethodsA cohort study was performed on healthy residents in Shangcheng County in Xinyang City from April to December in 2018, where the highest SFTS incidence in China was reported. Anti-SFTSV IgG was measured by indirect enzyme-linked immunosorbent assay and neutralizing antibody (NAb) was detected by using PRNT50. The logistic regression models were performed to analyze the variables that were associated with seropositive rates.ResultsTotally 886 individuals were recruited. The baseline seroprevalence that was tested before the epidemic season was 11.9% (70/587) for IgG and 6.8% (40/587) for NAb, which was increased to 13.4% (47/350) and 7.7% (27/350) during the epidemic season, and further to 15.8% (80/508) and 9.8% (50/508) post epidemic. The IgG antibody-based seropositivity was significantly related to the patients aged ≥ 70 years old [adjusted odds ratio (OR) = 2.440, 95% confidence interval (CI): 1.334–4.461 compared to the group of < 50 years old, P = 0.004], recent contact with cats (adjusted OR = 2.195, 95% CI: 1.261–3.818, P = 0.005), and working in tea garden (adjusted OR = 1.698, 95% CI: 1.002–2.880, P = 0.049) by applying multivariate logistic regression model. The NAb based seropositivity was similarly related to the patients aged ≥ 70 years old (adjusted OR = 2.691, 95% CI: 1.271–5.695 compared to the group of < 50 years old, P = 0.010), and recent contact with cats (OR = 2.648, 95% CI: 1.419–4.941, P = 0.002). For a cohort of individuals continually sampled with 1-year apart, the anti-SFTSV IgG were maintained at a stable level, while the NAb level reduced.ConclusionsSubclinical infection might not provide adequate immunity to protect reinfection of SFTSV, thus highlighting the ongoing threats of SFTS in endemic regions, which called for an imperative need for vaccine development. Identification of risk factors might help to target high-risk population for public health education and vaccination in the future.Graphical

Original antigenic sin responses to Betacoronavirus spike proteins are observed in a mouse model, but are not apparent in children following SARS-CoV-2 infection.

The effects of pre-existing endemic human coronavirus (HCoV) immunity on SARS-CoV-2 serologic and clinical responses are incompletely understood. We sought to determine the effects of prior exposure to HCoV Betacoronavirus HKU1 spike protein on serologic responses to SARS-CoV-2 spike protein after intramuscular administration in mice. We also sought to understand the baseline seroprevalence of HKU1 spike antibodies in healthy children and to measure their correlation with SARS-CoV-2 binding and neutralizing antibodies in children hospitalized with acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome (MIS-C). Groups of 5 mice were injected intramuscularly with two doses of alum-adjuvanted HKU1 spike followed by SARS-CoV-2 spike; or the reciprocal regimen of SARS-Cov-2 spike followed by HKU1 spike. Sera collected 21 days following each injection was analyzed for IgG antibodies to HKU1 spike, SARS-CoV-2 spike, and SARS-CoV-2 neutralization. Sera from children hospitalized with acute COVID-19, MIS-C or healthy controls (n = 14 per group) were analyzed for these same antibodies. Mice primed with SARS-CoV-2 spike and boosted with HKU1 spike developed high titers of SARS-CoV-2 binding and neutralizing antibodies; however, mice primed with HKU1 spike and boosted with SARS-CoV-2 spike were unable to mount neutralizing antibodies to SARS-CoV-2. HKU1 spike antibodies were detected in all children with acute COVID-19, MIS-C, and healthy controls. Although children with MIS-C had significantly higher HKU1 spike titers than healthy children (GMT 37239 vs. 7551, P = 0.012), these titers correlated positively with both SARS-CoV-2 binding (r = 0.7577, P<0.001) and neutralizing (r = 0.6201, P = 0.001) antibodies. Prior murine exposure to HKU1 spike protein completely impeded the development of neutralizing antibodies to SARS-CoV-2, consistent with original antigenic sin. In contrast, the presence of HKU1 spike IgG antibodies in children with acute COVID-19 or MIS-C was not associated with diminished neutralizing antibody responses to SARS-CoV-2.

COVID-19: Seroprevalence and Vaccine Responses in UK Dental Care Professionals

Dental care professionals (DCPs) are thought to be at enhanced risk of occupational exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, robust data to support this from large-scale seroepidemiological studies are lacking. We report a longitudinal seroprevalence analysis of antibodies to SARS-CoV-2 spike glycoprotein, with baseline sampling prior to large-scale practice reopening in July 2020 and follow-up postimplementation of new public health guidance on infection prevention control (IPC) and enhanced personal protective equipment (PPE). In total, 1,507 West Midlands DCPs were recruited into this study in June 2020. Baseline seroprevalence was determined using a combined IgGAM enzyme-linked immunosorbent assay and the cohort followed longitudinally for 6 mo until January/February 2021 through the second wave of the coronavirus disease 2019 pandemic in the United Kingdom and vaccination commencement. Baseline seroprevalence was 16.3%, compared to estimates in the regional population of 6% to 7%. Seropositivity was retained in over 70% of participants at 3- and 6-mo follow-up and conferred a 75% reduced risk of infection. Nonwhite ethnicity and living in areas of greater deprivation were associated with increased baseline seroprevalence. During follow-up, no polymerase chain reaction–proven infections occurred in individuals with a baseline anti–SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. After vaccination, antibody responses were more rapid and of higher magnitude in those individuals who were seropositive at baseline. Natural infection with SARS-CoV-2 prior to enhanced PPE was significantly higher in DCPs than the regional population. Natural infection leads to a serological response that remains detectable in over 70% of individuals 6 mo after initial sampling and 9 mo from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech 162b vaccine is associated with an antibody response indicative of immunological memory.

Anti-SARS-CoV-2 Antibodies Testing in Recipients of COVID-19 Vaccination: Why, When, and How?

Although universal vaccination is one of the most important healthcare strategies for limiting SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) circulation and averting the huge number of hospitalizations and deaths due to coronavirus disease 2019 (COVID-19), significant inter-individual variability of COVID-19 vaccines’ efficacies has been described, mostly due to heterogeneous immune response in recipients. This opinion paper hence aims to discuss aspects related to the opportunity of monitoring anti-SARS-CoV-2 antibodies before and after COVID-19 vaccination, highlighting the pros and cons of this strategy. In summary, the advantages of anti-SARS-CoV-2 antibodies’ testing in recipients of COVID-19 vaccination encompass an assessment of baseline seroprevalence of SARS-CoV-2 infection in non-vaccinated individuals; early identification of low or non-responders to COVID-19 vaccination; and timely detection of faster decay of anti-SARS-CoV-2 antibody levels. In contrast, potential drawbacks to date include an unproven equivalence between anti-SARS-CoV-2 antibody titer, neutralizing activity, and vaccine efficiency; the lack of cost-effective analyses of different testing strategies; the enormous volume of blood drawings and increase of laboratory workload that would be needed to support universal anti-SARS-CoV-2 antibodies testing. A potential solution entails the identification of cohorts to be prioritized for testing, including those at higher risk of being infected by variants of concern, those at higher risk of unfavorable disease progression, and subjects in whom vaccine immunogenicity may be expectedly lower and/or shorter.

Seropositivity in blood donors and pregnant women during the first year of SARS-CoV-2 transmission in Stockholm, Sweden.

BackgroundIn Sweden, social restrictions to contain SARS‐CoV‐2 have primarily relied upon voluntary adherence to a set of recommendations. Strict lockdowns have not been enforced, potentially affecting viral dissemination. To understand the levels of past SARS‐CoV‐2 infection in the Stockholm population before the start of mass vaccinations, healthy blood donors and pregnant women (n = 5,100) were sampled at random between 14 March 2020 and 28 February 2021.MethodsIn this cross‐sectional prospective study, otherwise‐healthy blood donors (n = 2,600) and pregnant women (n = 2,500) were sampled for consecutive weeks (at four intervals) throughout the study period. Sera from all participants and a cohort of historical (negative) controls (n = 595) were screened for IgG responses against stabilized trimers of the SARS‐CoV‐2 spike (S) glycoprotein and the smaller receptor‐binding domain (RBD). As a complement to standard analytical approaches, a probabilistic (cut‐off independent) Bayesian framework that assigns likelihood of past infection was used to analyse data over time.SettingHealthy participant samples were randomly selected from their respective pools through Karolinska University Hospital. The study was carried out in accordance with Swedish Ethical Review Authority: registration number 2020–01807.ParticipantsNo participants were symptomatic at sampling, and blood donors were all over the age of 18. No additional metadata were available from the participants.ResultsBlood donors and pregnant women showed a similar seroprevalence. After a steep rise at the start of the pandemic, the seroprevalence trajectory increased steadily in approach to the winter second wave of infections, approaching 15% of all individuals surveyed by 13 December 2020. By the end of February 2021, 19% of the population tested seropositive. Notably, 96% of seropositive healthy donors screened (n = 56) developed neutralizing antibody responses at titres comparable to or higher than those observed in clinical trials of SARS‐CoV‐2 spike mRNA vaccination, supporting that mild infection engenders a competent B‐cell response.ConclusionsThese data indicate that in the first year since the start of community transmission, seropositivity levels in metropolitan in Stockholm had reached approximately one in five persons, providing important baseline seroprevalence information prior to the start of vaccination.

Prevalence and Course of IgA and IgG Antibodies against SARS-CoV-2 in Healthcare Workers during the First Wave of the COVID-19 Outbreak in Germany: Interim Results from an Ongoing Observational Cohort Study.

(1) Background: Healthcare workers (HCWs) are prone to intensified exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the ongoing pandemic. We prospectively analyzed the prevalence of antibodies against SARS-CoV-2 in HCWs at baseline and follow up with regard to clinical signs and symptoms in two university hospitals in Brandenburg, Germany. (2) Methods: Screening for anti-SARS-CoV-2 IgA and IgG antibodies was offered to HCWs at baseline and follow up two months thereafter in two hospitals of Brandenburg Medical School during the first wave of the COVID-19 pandemic in Germany in an ongoing observational cohort study. Medical history and signs and symptoms were recorded by questionnaires and analyzed. (3) Results: Baseline seroprevalence of anti-SARS-CoV-2 IgA was 11.7% and increased to 15% at follow up, whereas IgG seropositivity was 2.1% at baseline and 2.2% at follow up. The rate of asymptomatic seropositive cases was 39.5%. Symptoms were not associated with general seropositivity for anti-SARS-CoV-2; however, class switch from IgA to IgG was associated with increased symptom burden. (4) Conclusions: The seroprevalence of antibodies against SARS-CoV-2 was low in HCWs but higher compared to population data and increased over time. Screening for antibodies detected a significant proportion of seropositive participants cases without symptoms.