IMMUNE DYSREGULATION FOLLOWING INFECTION BY THE NEW CORONAVIRUS SARS-CoV-2 (COVID-19); A NEW DISEASE ENTITY

Severe pneumonia by the novel coronavirus (COVID-19 infection) is mediated through immune dysregulation. It was studied if this dysregulation persists after recovery and if it is linked to the manifestation of post-covid syndrome (PCS). Patients who had been hospitalized for COVID-19 pneumonia 3 to 6 months ago during two different time periods and matched comparators were the derivation cohort (n=46, September-October 2020) and the validation cohort (n=484, April-July 2021) respectively. Peripheral blood mononuclear cells (PBMCs) were isolated for culture and cytokine stimulation. Patients provided answers to two health questionnaires allowing classification into PCS and were also subject to lung function tests (LFT). The primary endpoint was the modulation of the production of interleukin (IL)-1b and IL-6 from monocytes and among secondary, the modulation of adaptive immune response and the development of PCS. Increased production of IL-1b (p<0.001) and IL-6 (p<0.001) was found in both study periods compared to control. There was increase of pro-inflammatory Th1 responses over anti-inflammatory Th2 responses and attenuation of the T17 response. PCS was manifested in 22% of patients, grouped into three groups of symptoms. Fatigue was associated with the predominance of Th2 responses and abnormal LFT with overproduction of IL-1b and IL-6. Immune dysregulation is apparent after three months post COVID-19 pneumonia with main features the hyper-production of IL-1β and IL-6 by circulating monocytes, the increase of the Th1/Th2 ratio and the attenuation of T17 response.