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EClinicalMedicine ; 27: 100553, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1385448


BACKGROUND: Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia. METHODS: 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead. FINDINGS: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2/FiO2:146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2/FiO2: 112(IQR:100-141.5)].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 h, 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%. INTERPRETATION: IL-6R 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 outcome and good safety.

JCI Insight ; 6(13)2021 06 18.
Article in English | MEDLINE | ID: covidwho-1346128


We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post-COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1+ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14+ monocytes and development of PD-L1+ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post-COVID-19 pathology.

Arthritis, Rheumatoid/immunology , COVID-19/immunology , Monocytes/immunology , Neutrophils/immunology , Osteopontin/immunology , Arthritis, Rheumatoid/metabolism , B7-H1 Antigen/immunology , Bronchoalveolar Lavage Fluid/immunology , CD48 Antigen/immunology , COVID-19/chemically induced , COVID-19/metabolism , Fatty Acid-Binding Proteins/immunology , Humans , Lectins/immunology , Lipopolysaccharide Receptors/immunology , Lipopolysaccharide Receptors/metabolism , Lung/diagnostic imaging , Lung/immunology , Lung/metabolism , Lung/pathology , Macrophages/immunology , Macrophages/metabolism , Membrane Glycoproteins/immunology , Monocytes/metabolism , Neutrophils/metabolism , Osteopontin/blood , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Immunologic/immunology , S100A12 Protein/immunology , S100A12 Protein/metabolism , Synovial Membrane/immunology , Tomography, X-Ray Computed
Eur J Clin Invest ; 50(9): e13342, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-636108


COVID-19 pandemia is a major concern for patients and healthcare systems. The fear of infection by patients with concomitant rheumatic diseases (either adult or children) and connective tissue diseases is arising worldwide, because of their immunological background and immunological therapies. Analysing the basic biology of single diseases, the data suggest that there is an "immunological umbrella" that seems to protect against the infection, through IFN type 1 and NK cell function. To date, reports from China, United States and Europe did not reveal an higher risk of infection, either for rheumatoid arthritis, juvenile idiopathic arthritis nor for lupus erythematosus. Antimalarials, anti-IL6-Anti-IL6 receptor, anti-IL1, anti-GM-CSF receptor and JAK1/2/3 inhibitors, are under investigation in COVID-dedicated clinical trials to control the inflammation raised by SARS-CoV-2 infection. Initial reports on the occurrence of autoimmune phenomena in the convalescence phase of SARS-CoV-2 infection suggests that the immunological consequences of the infection need to be strictly understood. Reporting of the study conforms to broad EQUATOR guidelines (Simera et al January 2010 issue of EJCI).

Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Immunosuppressive Agents/administration & dosage , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Rheumatic Diseases/epidemiology , Severe Acute Respiratory Syndrome/epidemiology , Adaptive Immunity/drug effects , Adaptive Immunity/immunology , Aged , Antirheumatic Agents/administration & dosage , COVID-19 , Comorbidity , Coronavirus Infections/drug therapy , Disease Outbreaks/statistics & numerical data , Female , Humans , Hydroxychloroquine/administration & dosage , Immunity, Innate/drug effects , Immunity, Innate/immunology , Immunologic Factors/administration & dosage , Italy/epidemiology , Male , Middle Aged , Pandemics , Pneumonia, Viral/drug therapy , Rheumatic Diseases/drug therapy , Rheumatic Diseases/immunology , Risk Assessment , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/immunology