RESUMO
After more than two years the COVID-19 pandemic continues to burden healthcare systems and economies worldwide, and it is evident that long-term effects of the disease can persist for months post-recovery in some individuals. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to SARS-CoV-2 is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19. Here, we followed, for 6-7 months, a cohort of COVID-19 patients hospitalized during the early waves of the pandemic. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection. We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in PD-L1 expression but increased CD86 expression across almost all cell types examined. Finally, viral load and CRP correlated to the appearance of circulating antibodies and levels of circulating DC and monocyte subsets, respectively. By elucidating some of the long-term effects that SARS-CoV-2 infection has on these key innate myeloid cells, we have shed more light on how the immune landscape remains affected in the months following severe COVID-19.
RESUMO
COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8+ TEMRA and exhausted CD57+CD8+ T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T-cell activation were upregulated at the inclusion, and in the case of CD69+CD4+ T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.
RESUMO
BackgroundThe COVID-19 pandemic has highlighted the need for rapid, cost effective and easy-to-use diagnostic tools for SARS-CoV-2 rapid antigen detection (RAD) for use in point of care settings or as self-tests, to limit disease transmission. Using saliva samples would further greatly facilitate sample collection, diagnostic feasibility, and mass screening. ObjectiveWe tested two rapid antigen immunochromatographic tests designed for detection of SARS-CoV-2 in saliva: Rapid Response COVID-19 Antigen Rapid Test Cassette for oral fluids (Rapid Response) and DIAGNOS COVID-19 Antigen Saliva Test (DIAGNOS). Evaluation of detection limit was performed with purified SARS-CoV-2 nucleocapsid protein and titrated live SARS-CoV-2 virus and compared to Abbott Panbio COVID-19 Ag Rapid Test (Panbio) designed for nasopharyngeal samples. Sensitivity and specificity were further evaluated on RT-qPCR positive and negative saliva samples from individuals hospitalized with COVID-19 (n=34); and asymptomatic health care personnel (n=20). ResultsThe limit of detection of the saliva test from DIAGNOS was comparable with the Panbio test and showed higher sensitivity than Rapid Response for both nucleocapsid protein and diluted live viruses. DIAGNOS and Rapid Response further detected seven (47%) and five (33%), respectively, of the 15 RT-qPCR positive saliva samples in individuals hospitalized with COVID-19. Of the 39 RT-qPCR negative samples, all were negative with both tests (specificity 100%; 95% c.i. 0.91-1.00). Only one of the RT-qPCR positive saliva samples (Ct 21.6) contained infectious virus as determined by cell culture and was also positive using the saliva RADs. ConclusionThe results show that the DIAGNOS test exhibit a similar limit of detection as the Panbio RAD and may be an important and easy-to-use saliva RAD complement to detect infectious individuals.
