Immune Profile of COVID-19 Survivors and Contacts During 9 Months:A Cohort Study

Background:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)causes a multi-organ systemic damage that can lead to long-term consequences.Little is known about the possible long-term effects of COVID-19 on circulating leukocyte kinetics and functional T-cell activity after recovery.To investigate immune system changes,we designed a cohort study.Methods:Volunteer screening and sample collectionwere performed at the Irkutsk Research Anti-Plague Institute of Rospotrebnadzor.Sixty-four volunteers who have had COVID-19(recovered volunteers(RVs))betweenMay 2020 andMay 2021,33 volunteers who had been in contact with COVID-19 patients(contact volunteers(CVs))within the family setting but had not become ill,and 47 healthy volunteers(HVs)participated in the study.We performed immunophenotyping of peripheral blood cells using flow cytometry.Serum was tested for SARS-CoV-2 anti-nucleocapsid immunoglobulin G antibodies by enzyme-linked immunosorbent assay(Ab(+),people with specific anti-N antibodies to SARS-CoV-2;Ab(−),people without specific antibodies).Results:There were no serious disturbances in the internal environment of the body in RVs and CVs.In the evaluation of the general state of the immune system,the most informative indicator was the index of the ratio of neutrophils to bloodmonocytes–decreased on the 1st terms of observation(1 and 3 months post-symptom onset(PSO)/post-contact onset(PCO)),on average,1.3 times compared with HVs(8.6%(7.5%–10.5%),P<0.05),which recovered by the 6th month of observation.Redistribution of the cells responsible for the development of the adaptive immune response was noted only in RVs–increased B-lymphocyte content(HVs,9.1%(6.4%–10.2%))and immunoregulatory index ratio(HVs,1.6%(1.2%–2.1%))due to redistribution of T-helper and cytotoxic T cells throughout the follow-up period by an average of 1.2-fold compared with HVs(P<0.05).However,CVs with specific antibodies to SARS-CoV-2 N-protein also had an increased proportion of CD3−CD19+cells after 1 month PCO(Ab(+),11.4%(10.2%–15.1%);Ab(−),8.6%(5.7%–9.7%);P=0.006).A significant difference between RVs and CVs is that the RVs showed significant activation of circulating T cells,which persisted up to the 6th month of the study,whereas in CVs,it persisted for 3 months PCO.The highest proportion ofHLA-DR+T-lymphocyteswas recorded after 1month PSO/PCOin Ab(+)RVs andCVs:Ab(+)volunteers,8.1%(6.0%–11.2%)and 4.4%(2.7%–6.4%),respectively;Ab(−)volunteers,4.2%(2.6%–5.4%)and 5.1%(3.7%–5.6%);and HVs,3.5%(2.5%–4.7%)(P<0.01).In CVs,natural killer cells also played a major role in preventing manifest infection(CVs,10.8%±4.3%;HVs,15.9%±7.6%;P<0.05).Conclusion:In this study,we demonstrated the dynamics of returning to the initial state of health in RVs and CVs.In CVs,we observed changes in the studied immunological parameters similar to those of RVs,butwhich are less intense and prolonged.Complete recovery of the studied immunological parameters occurs within 6 months.