UNVACCINATED PATIENTS WITH SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASES HAVE HETEROGENEOUS AND UNRELATED RISKS OF COVID INFECTION AND POOR OUTCOME (preprint)

Background: The impact of the severe acute respiratory syndrome Coronavirus 2 disease (COVID-19) pandemic on people with systemic autoimmune rheumatic diseases (SARDs) is not fully established. It is unclear whether SARDs are an independent risk factor for infection and poor outcomes. Methods: Incidence and 30-day outcomes of COVID-19 infection were retrospectively evaluated in 40,490 SARD patients in the Lazio Italian Region and compared to the general population as incidence rate ratio adjusted for demographics and comorbidities (adjIRR). SARD diagnosis and comorbidities were derived from medical administrative records using the Chronic Related Group classification system. Data on COVID-19 infection were derived from a dedicated regional digital network. Results: The COVID-19 infection risk was increased in patients with Psoriatic Arthritis (adjIRR=1.21, 95% CI 1.10-1.33) and Undifferentiated Connective Tissue Disease (adjIRR=1.26, 95% CI 1.03-1.54). The hospitalization risk was higher in patients with Axial Spondylarthritis (adjIRR=2.16, 95% CI 1.45-3.22), and Systemic Vasculitis (adjIRR=1.81, 95% CI 1.07-3.06) while intensive care unit admission risk was higher in Systemic Erythematosus Lupus (adjIRR=3.67, 95% CI 1.52-8.83) and primary Sjögren Syndrome (adjIRR=4.13, 95% CI 1.71-9.96) patients. Increased mortality was reported in patients with Rheumatoid Arthritis (adjIRR=1.50, 95% CI 1.04-2.17), Systemic Erythematosus Lupus (adjIRR=2.67, 95% CI 1.10-6.44), primary Sjögren Syndrome (adjIRR=2.51, 95% CI 1.12-5.62), and Scleroderma (adjIRR=4.60, 95% CI 2.06-10.29). Conclusions: Each SARDs presents a peculiar pattern in terms of increased risk of COVID-19 incidence, hospitalization, intensive care unit admission, and death, that is not linked to the immunosuppressive behaviour of the disease.

Sarilumab use in severe SARS-CoV-2 pneumonia (preprint)

Importance: Interleukin-6 signal blockade has shown preliminary beneficial effects in treating aberrant host inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Objective: to describe the effect of off-label intravenous use of Sarilumab in patients with severe SARS-CoV-2-related pneumonia. Design: Observational clinical cohort study. Setting: Fondazione Policlinico Universitario A. Gemelli IRCCS as Italian Covid reference center. Participants: Patients with laboratory-confirmed SARS-CoV-2 infection and respiratory distress with PaO2/FiO2 ratio<300 treated with Sarilumab between March 23rd - April 4th, 2020. Date of final follow-up was April 18, 2020. Main outcomes and measures: We describe the clinical outcomes of 53 patients with SARS-CoV-2 severe pneumonia treated with intravenous Sarilumab in terms of pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards setting and of live discharge rate in ICU treated patients as well as in terms of safety. Each patient received Sarilumab 400 mg administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and was followed for at least 14 days, unless previously discharged or dead. No gluco-corticosteroids were used at baseline. Results: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39 (73.6%) were treated in medical wards (66.7% with a single infusion) while 14 (26.4%) in ICU (92.6% with a second infusion). The median PaO2/FiO2 of patients in the Medical Ward was 146(IQR:120-212) while the median PaO2/FiO2 of patients in ICU was 112(IQR:100-141.5), respectively. Within the medical wards, 7(17.9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89.7% of medical inpatients significantly improved (46.1% after 24 hours, 61.5% after 3 days), 70.6% were discharged from the hospital and 85.7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64.2% were discharged from ICU to the ward and 35.8% were still alive at the last follow-up. Overall mortality rate was 5.7% after Sarilumab administration: 1(2.5%) patient died in the Medical Ward whilst 2(14.2%) patients died in ICU, respectively. Conclusions and relevance: IL6-R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical benefit and good safety.