Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Reversed halo sign as initial manifestation of interstitial pneumonitis associated with Sjögren’s syndrome

Introduction: Sjögren’s syndrome (SS) is a chronic autoimmune multisystemic disease. Respiratory manifestations of SS are polymorphic and vary in severity. Among the possible manifestations, organizing pneumonia (OP) is a rare entity. Reversed halo sign (RHS) is an unusual radiological finding classically related to OP but it is also reported in other forms of interstitial pneumonitis (IP). Case presentation: We report a case of a 65-year-old woman with dyspnoea and persistent-cough of 2-month duration. She presented with RHS as an initial manifestation of IP related to SS. Chest radiography and computer tomography showed multiple well defined lesions with a central ground glass area and peripheral rim of consolidation. No pathological lymph nodes were found. After investigations, the associated diagnosis of SS was confirmed. The patient started steroids (0.5 mg/kg/day) and after 10 weeks of steroid tapering a significant clinical improvement was observed, with radiological resolution of lung lesions. We make some general considerations about differential diagnosis, conditions related to RHS and different patterns of lung involvement in SS. A report of the literature emphasizes this case as an exceptional way of presentation. Conclusion: To the best of our knowledge this is the second reported OP case associated with SS manifesting as RHS. RSH as an expression of IP related to SS is exceptional, either in the pattern of OP or non-specific IP