Combinatorial analysis reveals highly coordinated early-stage immune reactions that predict later antiviral immunity in mild COVID-19 patients

in Cell Reports Medicine (2022), 3(4), 100600

While immunopathology has been widely studied in patients with severe COVID-19, immune responses in non-hospitalized patients have remained largely elusive. We systematically analyze 484 peripheral ... [more ▼]

While immunopathology has been widely studied in patients with severe COVID-19, immune responses in non-hospitalized patients have remained largely elusive. We systematically analyze 484 peripheral cellular or soluble immune features in a longitudinal cohort of 63 mild and 15 hospitalized patients versus 14 asymptomatic and 26 household controls. We observe a transient increase of IP10/CXCL10 and interferon-β levels, coordinated responses of dominant SARS-CoV-2-specific CD4 and fewer CD8 T cells, and various antigen-presenting and antibody-secreting cells in mild patients within 3 days of PCR diagnosis. The frequency of key innate immune cells and their functional marker expression are impaired in hospitalized patients at day 1 of inclusion. T cell and dendritic cell responses at day 1 are highly predictive for SARS-CoV-2-specific antibody responses after 3 weeks in mild but not hospitalized patients. Our systematic analysis reveals a combinatorial picture and trajectory of various arms of the highly coordinated early-stage immune responses in mild COVID-19 patients. [less ▲]

SARS-CoV-2 transmission risk from asymptomatic carriers: Results from a mass screening programme in Luxembourg

in The Lancet Regional Health. Europe (2021), 4

Background To accompany the lifting of COVID-19 lockdown measures, Luxembourg implemented a mass screening (MS) programme. The first phase coincided with an early summer epidemic wave in 2020. Methods rRT ... [more ▼]

Background To accompany the lifting of COVID-19 lockdown measures, Luxembourg implemented a mass screening (MS) programme. The first phase coincided with an early summer epidemic wave in 2020. Methods rRT-PCR-based screening for SARS-CoV-2 was performed by pooling of samples. The infrastructure allowed the testing of the entire resident and cross-border worker populations. The strategy relied on social connectivity within different activity sectors. Invitation frequencies were tactically increased in sectors and regions with higher prevalence. The results were analysed alongside contact tracing data. Findings The voluntary programme covered 49 of the resident and 22 of the cross-border worker populations. It identified 850 index cases with an additional 249 cases from contact tracing. Over-representation was observed in the services, hospitality and construction sectors alongside regional differences. Asymptomatic cases had a significant but lower secondary attack rate when compared to symptomatic individuals. Based on simulations using an agent-based SEIR model, the total number of expected cases would have been 42·9 (90 CI [-0·3, 96·7]) higher without MS. Mandatory participation would have resulted in a further difference of 39·7 [19·6, 59·2]. Interpretation Strategic and tactical MS allows the suppression of epidemic dynamics. Asymptomatic carriers represent a significant risk for transmission. Containment of future outbreaks will depend on early testing in sectors and regions. Higher participation rates must be assured through targeted incentivisation and recurrent invitation. Funding This project was funded by the Luxembourg Ministries of Higher Education and Research, and Health. [less ▲]