Stijn P. Andeweg’s research while affiliated with National Institute for Public Health and the Environment and other places

Fatigue is one of the most common persistent symptoms of SARS-CoV-2 infection. We aimed to assess fatigue during and after a SARS-CoV-2 infection by age, sex, presence of a medical risk condition, SARS-CoV-2 variant and vaccination status, accounting for pre-infection fatigue and compared with uninfected individuals. We used data from an ongoing prospective cohort study in the Netherlands (VASCO). We included 22,705 first infections reported between 12 July 2021 and 9 March 2024. Mean fatigue scores increased during infection, declined rapidly in the first 90 days post-infection, but remained elevated until at least 270 days for Delta and 120 days for Omicron infections. Prevalence of severe fatigue was 18.5% before first infection. It increased to 24.4% and 22.5% during acute infection and decreased to 21.2% and 18.9% at 90 days after Delta and Omicron infection, respectively. The prevalence among uninfected participants was lower than among matched Delta-infected participants during the acute phase of the infection and 90 days post-infection. For matched Omicron-infected individuals this was only observed during the acute phase. We observed no differences in mean post- vs pre-infection fatigue scores at 90-270 days post-infection by vaccination status. The impact of SARS-CoV-2 infection on the prevalence of severe fatigue was modest at population level, especially for Omicron.

We assessed the validity of serum total anti-nucleoprotein Immunoglobulin (N-antibodies) to identify SARS-CoV-2 (re)infections by estimating the persistence of N-antibody seropositivity and boosting following infection. From a prospective Dutch cohort study (VASCO), we included adult participants with ≥2 consecutive self-collected serum samples, 4–8 months apart, between May 2021–May 2023. Sample pairs were stratified by N-seropositivity of the first sample and by self-reported infection within the sampling interval. We calculated the proportions of participants with N-seroconversion and fold-increase (1.5, 2, 3, 4) of N-antibody concentration over time since infection and explored determinants. We included 67,632 sample pairs. Pairs with a seronegative first sample (70%) showed 89% N-seroconversion after reported infection and 11% when no infection was reported. In pairs with a seropositive first sample (30%), 82%–65% showed a 1.5- to 4-fold increase with a reported reinfection, and 19%–10% without a reported reinfection, respectively. After one year, 83% remained N-seropositive post-first infection and 93%–61% showed a 1.5-fold to 4-fold increase post-reinfection. Odds for seroconversion/fold increase were higher for symptomatic infections and Omicron infections. In the current era with limited antigen or PCR testing, N-serology can be validly used to detect SARS-CoV-2 (re)infections at least up to a year after infection, supporting the monitoring of COVID-19 burden and vaccine effectiveness.

Immunity induced by vaccination and infection, referred to as hybrid immunity, provides better protection against SARS-CoV-2 infections compared to immunity induced by vaccinations alone. To assess the development of hybrid immunity we investigated the induction of Nucleoprotein-specific antibodies in PCR-confirmed infections by Delta or Omicron in vaccinated individuals (n = 520). Eighty-two percent of the participants with a breakthrough infection reached N-seropositivity. N-seropositivity was accompanied by Spike S1 antibody boosting, and independent of vaccination status or virus variant. Following the infection relatively more antibodies to the infecting virus variant were detected. In conclusion, these data show that hybrid immunity through breakthrough infections is hallmarked by Nucleoprotein antibodies and broadening of the Spike antibody repertoire. Exposure to future SARS-CoV-2 variants may therefore continue to maintain and broaden vaccine-induced population immunity.

Background Information on the magnitude and duration of antibody levels after COVID-19 vaccination in different groups may be useful for prioritizing of additional vaccinations. Methods Serum samples were collected every six months in a prospective cohort study among adults in the Netherlands. Geometric mean concentrations (GMCs) of antibodies against the receptor binding domain of the SARS-CoV-2 spike protein were calculated after the primary series, first, and second booster vaccinations. Effects of age (18-59 vs 60-85 years) and medical risk conditions on GMC 2-6 weeks and 21-25 weeks after each vaccination, and on waning during 3-25 weeks after each vaccination, were estimated by linear regression. Results We included 20,816, 16,820 and 5,879 samples collected after primary, first and second booster vaccination, respectively. GMCs at 2-6 and 21-25 weeks after primary series were lower in participants with older age or medical risk conditions. After the first booster, older age was associated with lower GMC at 2-6 weeks, higher GMC at 21-25 weeks, and slower waning. GMCs or waning after the first and second boosters (only 60-85) were not associated with medical risk conditions. Conclusions Since antibody differences by age and medical risk groups have become small with increasing number of doses, other factors such as disease severity rather than antibody levels are useful for prioritization of additional vaccinations.

During the COVID-19 pandemic, contact tracing was used to identify individuals who had been in contact with a confirmed case so that these contacted individuals could be tested and quarantined to prevent further spread of the SARS-CoV-2 virus. Many countries developed mobile apps to find these contacted individuals faster. We evaluate the epidemiological effectiveness of the Dutch app CoronaMelder, where we measure effectiveness as the reduction of the reproduction number R. To this end, we use a simulation model of SARS-CoV-2 spread and contact tracing, informed by data collected during the study period (December 2020 - March 2021) in the Netherlands. We show that the tracing app caused a clear but small reduction of the reproduction number, and the magnitude of the effect was found to be robust in sensitivity analyses. The app could have been more effective if more people had used it, and if time intervals between symptom onset and reporting of contacts would have been shorter. The model used is novel as it accounts for the clustered nature of social networks and as it accounts for cases informally alerting their contacts directly after symptom onset, without involvement of health authorities or a tracing app.

Immunity induced by vaccination and infection, referred to as hybrid immunity, provides better protection against SARS-CoV-2 infections compared to immunity induced by vaccinations alone. To assess the development of hybrid immunity we investigated the induction of Nucleoprotein-specific antibodies in PCR-confirmed infections by Delta or Omicron in vaccinated individuals (n = 520). Eighty-two percent of the participants with a breakthrough infection reached N-seropositivity. N-seropositivity was accompanied by Spike S1 antibody boosting, and independent of vaccination status or virus variant. Following the infection relatively more antibodies to the infecting virus variant were detected. In conclusion, these data show that hybrid immunity through breakthrough infections is hallmarked by Nucleoprotein antibodies and repertoire broadening of Spike antibodies. Exposure to future SARS-CoV-2 variants may therefore continue to maintain and broaden vaccine-induced population immunity.

Background: Children play a key role in the transmission of many infectious diseases. They have many of their close social encounters at home or at school. We hypothesized that most of the transmission of respiratory infections among children occur in these two settings and that transmission patterns can be predicted by a bipartite network of schools and households. Aim and methods: To confirm transmission over a school-household network, SARS-CoV-2 transmission pairs in children aged 4-17 years were analyzed by study year and primary/secondary school. Cases with symptom onset between 1 March 2021 and 4 April 2021 identified by source and contact-tracing in the Netherlands were included. In this period, primary schools were open and secondary school students attended class at least once per week. Within pairs, spatial distance between the postcodes was calculated as the Euclidean distance. Results: A total of 4059 transmission pairs were identified; 51.9% between primary schoolers; 19.6% between primary and secondary schoolers; 28.5% between secondary schoolers. Most (68.5%) of the transmission for children in the same study year occurred at school. In contrast, most of the transmission of children from different study years (64.3%) and most primary-secondary transmission (81.7%) occurred at home. The average spatial distance between infections was 1.2 km (median 0.4) for primary school pairs, 1.6 km (median 0) for primary-secondary school pairs and 4.1 km (median 1.2) for secondary school pairs. Conclusion: The results provide evidence of transmission on a bipartite school-household network. Schools play an important role in transmission within study years, and households play an important role in transmission between study years and between primary and secondary schools. Spatial distance between infections in a transmission pair reflects the smaller school catchment area of primary schools versus secondary schools. Many of these observed patterns likely hold for other respiratory pathogens.