Protective Reactive Thymus Hyperplasia in the COVID-19 Acute Respiratory Distress Syndrome

Abstract Background. COVID-19 (COVID) patients can develop acute respiratory distress syndrome associated or not with sepsis, coagulopathy and visceral injuries. While thoracic CT-scans are routinely performed in the initial evaluation of patients with severe pulmonary forms, thymus involvement and reactivation have not been investigated so far.Methods. In this observational study, we systematically scored the thymus enlargement and the lung involvement, using CT-scans, in all adult patients admitted in ICU for COVID or any other cause (control group) in one center between March and April 2020. Initial biological investigations included nasal detection of SARS-CoV-2 ribonucleic acid detection by positive polymerase chain reaction (PCR). In a subgroup of 24 patients with different degrees of pulmonary involvement and thymus hypertrophy, plasma cytokines concentrations were measured and mature T-cell export from the thymus was estimated simultaneously by PCR quantification of T-cell receptor excision circles (TRECs).Results. Eighty-seven patients were studied: 50 COVID patients and 37 controls. Non-atrophic or enlarged thymus was more frequent in COVID patients than in controls (66% vs. 24%, p<0.0001). Thymus enlargement in COVID patients was associated with more extensive pulmonary involvement score on CT-scans 4 [3-5] vs. 2 [1.5-4], p=0.01, but lower mortality (8.6% versus 41.2%, p<0.001). Other factors associated with mortality were age, lymphopenia, high CRP and co-morbidities. COVID patients had higher concentrations of IL-7: 6.00 [3.72-9.25] vs. 2.17 [1.76-4.4] pg/mL; p=0.04, and higher thymic production of new lymphocytes: TRECS ratio = 2.88 [1.98-4.51] vs. 0.23 [0.15-0.60]; p=0.004. This thymic production was also correlated to the CT-scan thymic score (r = 0.38, p=0.03) and inversely correlated to the lymphocyte count (r=0.56, p=0.007).Conclusions. In COVID patients, thymus enlargement was frequent and associated with increased T-lymphocytes production that appears a beneficial adaptation to virus-induced lymphopenia. The loss of thymic reactivation might contribute to worse prognosis.Trial registration: NA