Abstract
BackgroundPatients with COVID-19 (COVID) may develop acute respiratory distress syndrome with or without sepsis, coagulopathy and visceral damage. While chest CT scans are routinely performed in the initial assessment of patients with severe pulmonary forms, thymus involvement and reactivation have not been investigated so far.MethodsIn this observational study, we systematically scored the enlargement of the thymus and the lung involvement, using CT scans, in all adult patients admitted to the ICU for COVID or any other cause (control group) at one centre between March and April 2020. Initial biological investigations included nasal detection of SARS-CoV-2 ribonucleic acid by polymerase chain reaction (PCR). In a subgroup of 24 patients with different degrees of pulmonary involvement and thymus hypertrophy, plasma cytokine concentrations were measured and the export of mature T cells from the thymus was estimated simultaneously by PCR quantification of T cell receptor excision circles (TRECs).ResultsEighty-seven patients were studied: 50 COVID patients and 37 controls. Non-atrophic or enlarged thymus was more commonly observed in COVID patients than in controls (66% vs. 24%, p < 0.0001). Thymus enlargement in COVID patients was associated with more extensive lung injury score on CT scans (4 [3–5] vs. 2 [1.5–4], p = 0.01), but a lower mortality rate (8.6% vs. 41.2%, p < 0.001). Other factors associated with mortality were age, lymphopaenia, 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 (sj/βTREC ratio = 2.88 [1.98–4.51] vs. 0.23 [0.15–0.60]; p = 0.004). Thymic production was also correlated with the CT scan thymic score (r = 0.38, p = 0.03) and inversely correlated with the number of lymphocytes (r = 0.56, p = 0.007).ConclusionIn COVID patients, thymus enlargement was frequent and associated with increased T lymphocyte production, which appears to be a beneficial adaptation to virus-induced lymphopaenia. The lack of thymic activity/reactivation in older SARS-CoV-2 infected patients could contribute to a worse prognosis.
Highlights
Less than one year after the beginning of the coronavirus 2019 pandemic (COVID) due to the virus identified as SARS-CoV-2, an increasing number of studies has markedly improved our knowledge of its epidemiology and illustrated the large spectrum of clinical consequences of the infection
The goal of this study was to quantify the enlargement of the thymus in all chest CT scans performed in patients admitted to our intensive care unit in March and April 2020, and to compare the CT scan scores of COVID patients with those of patients hospitalised for other reasons
We found that 66% of COVID patients hospitalised in our intensive care unit (ICU) displayed a surprisingly large thymus
Summary
Less than one year after the beginning of the coronavirus 2019 pandemic (COVID) due to the virus identified as SARS-CoV-2, an increasing number of studies has markedly improved our knowledge of its epidemiology and illustrated the large spectrum of clinical consequences of the infection. Recent investigations have highlighted the role of increased pro-inflammatory cytokines (cytokine storm) [5, 6], impaired type I interferon responses [7], profoundly altered T cell phenotypes [8] and functional exhaustion of antiviral lymphocytes [9, 10] in the severity of COVID. These findings, similar to those reported in previous pathogenic human coronavirus epidemics due to SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV), reflect the shift from a protective regulated inflammatory response against the virus to pathogenic dysregulated inflammation [11]. While chest CT scans are routinely performed in the initial assessment of patients with severe pulmonary forms, thymus involvement and reactivation have not been investigated so far
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