Sex-specific differences in physiological parameters related to SARS-CoV-2 infections among a national cohort (COVI-GAPP study) (preprint)

Considering sex as a biological variable in modern digital health solutions, we investigated sex-specific differences in the trajectory of four physiological parameters across a COVID-19 infection. A wearable medical device measured breathing rate, heart rate, heart rate variability, and wrist skin temperature in 1163 participants (mean age = 44.1 years, standard deviation [SD]=5.6; 667 [57%] females). Participants reported daily symptoms and confounders in a complementary app. A machine learning algorithm retrospectively ingested daily biophysical parameters to detect COVID-19 infections. COVID-19 serology samples were collected from all participants at baseline and follow-up. We analysed potential sex-specific differences in physiology and antibody titres using multilevel modelling and t-tests. Over 1.5 million hours of physiological data were recorded. During the symptomatic period of infection, men demonstrated larger increases in skin temperature, breathing rate and heart rate as well as larger decreases in heart rate variability than women. The COVID-19 infection detection algorithm performed similarly well for men and women. Our study belongs to the first research to provide evidence for differential physiological responses to COVID-19 between females and males, highlighting the potential of wearable technology to inform future precision medicine approaches. This work has received support from the Princely House of the Principality of Liechtenstein, the government of the Principality of Liechtenstein, the Hanela Foundation in Switzerland, and the Innovative Medicines Initiative (IMI) 2 Joint Undertaking under grant agreement No 101005177. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA.

Vaccine effectiveness of primary and booster COVID-19 vaccinations against SARS-CoV-2 infection in the Netherlands from 12 July 2021 to 6 June 2022: a prospective cohort study (preprint)

Introduction - Monitoring of COVID-19 vaccine effectiveness (VE) is needed to inform vaccine policy. We estimated VE of primary vaccination, and first and second booster vaccination, against SARS-CoV-2 infection overall, and in four risk groups defined by age and medical risk condition, in the Delta and Omicron BA.1/BA.2 periods. Methods - VASCO is an ongoing prospective cohort study among vaccinated and unvaccinated Dutch adults. The primary endpoint was a self-reported positive SARS-CoV-2 test during 12 July 2021-6 June 2022. Participants with a prior SARS-CoV-2 infection, based on a positive test or serology, were excluded. We used Cox proportional hazard models with vaccination status as time-varying exposure and adjustment for age, sex, educational level, and medical risk condition. We stratified by Delta and Omicron BA.1/BA.2 periods, risk group, and time since vaccination. Results - 37,170 participants (mean age 57 years) were included. In the Delta period, VE <6 weeks after primary vaccination was 80% (95%CI 69-87) and decreased to 71% (65-77) after 6 months. VE increased to 96% (86-99) shortly after the first booster vaccination. In the Omicron period these estimates were 46% (22-63), 25% (8-39) and 57% (52-62), respectively. VE was 50% (34-62) <6 weeks after a second booster vaccination in participants aged [≥]60 years. For the Omicron period, an interaction term between vaccination status and risk group significantly improved the model (p<0.001), with generally lower VEs for those with a medical risk condition. Conclusions - Our results show the benefit of booster vaccinations against infection, also in risk groups, although the additional protection wanes quite rapidly.

Cohort profile: an observational population-based cohort study on COVID-19 vaccine effectiveness in the Netherlands – The VAccine Study COvid-19 (VASCO) (preprint)

Purpose - VAccine Study COvid-19 (VASCO) is a cohort study with 5-year follow-up that was initiated when COVID-19 vaccination was introduced in the Netherlands. The primary objective is to estimate real-world vaccine effectiveness (VE) of COVID-19 vaccines against SARS-CoV-2 infection in the Netherlands, overall and in four subpopulations defined by age and medical risk. Participants - The cohort consists of 45,547 community-dwelling participants aged 18-85 years who were included irrespective of their COVID-19 vaccination status or intention to get vaccinated. A medical risk condition is present in 4,289 (19.8%) of 21,679 18-59 year-olds and in 9,135 (38.3%) of 23,821 60-85 year-olds. After one year of follow-up, 5,502 participants had dropped out of the study. At inclusion, and several times after inclusion, participants are asked to take a self-collected fingerprick blood sample in which nucleoprotein and spike protein receptor binding domain-specific antibody titers are assessed. Participants are also asked to complete monthly digital questionnaires in the first year, and 3-monthly in years 2-5, including questions on sociodemographic factors, health status, COVID-19 vaccination, SARS-CoV-2-related symptoms and testing results, and behavioral responses to COVID-19 measures. Findings to date - VASCO data has been used to describe VE against SARS-CoV-2 infection of primary vaccination, first and second booster and bivalent boosters, the impact of hybrid immunity on SARS-CoV-2 infection and VE against infectiousness. Furthermore, data was used to describe antibody response following vaccination and breakthrough infections and to investigate the relation between antibody response and reactogenicity. Future plans - VASCO will be able to contribute to policy decision-making regarding future COVID-19 vaccination. Furthermore, VASCO provides an infrastructure to conduct further studies and to anticipate on changing vaccination campaigns and testing policy, and new virus variants. Registration - VASCO is registered in the online Dutch clinical trials register (trialsearch.who.int) with registration number NL9279.