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Moderate or Severe Impairment in Pulmonary Function is Associated with Mortality in Sarcoidosis Patients Infected with SARS?CoV?2.

ABSTRACT: PURPOSE:To investigate whether sarcoidosis patients infected with SARS-CoV-2 are at risk for adverse disease outcomes. STUDY DESIGN AND METHODS:This retrospective study was conducted in five hospitals within the Mount Sinai Health System during March 1, 2020 to July 29, 2020. All patients diagnosed with COVID-19 were included in the study. We identified sarcoidosis patients who met diagnostic criteria for sarcoidosis according to accepted guidelines. An adverse disease outcome was defined as the presence of intubation and mechanical ventilation or in-hospital mortality. In sarcoidosis patients, we reported (when available) the results of pulmonary function testing measured within 3 years prior to the time of SARS?CoV?2 infection. A multivariable logistic regression model was used to generate an adjusted odds ratio (aOR) to evaluate sarcoidosis as a risk factor for an adverse outcome. The same model was used to analyze sarcoidosis patients with moderate and/or severe impairment in pulmonary function. RESULTS:The study included 7337 patients, 37 of whom (0.5%) had sarcoidosis. The crude rate of developing an adverse outcome was significantly higher in patients with moderately and/or severely impaired pulmonary function (9/14 vs. 3/23, p?=?0.003). While the diagnosis of sarcoidosis was not independently associated with risk of an adverse event, (aOR 1.8, 95% CI 0.9-3.6), the diagnosis of sarcoidosis in patients with moderately and/or severely impaired pulmonary function was associated with an adverse outcome (aOR 7.8, 95% CI 2.4-25.8). CONCLUSION:Moderate or severe impairment in pulmonary function is associated with mortality in sarcoidosis patients infected with SARS?CoV?2.

SUBMITTER: Morgenthau AS

PROVIDER: S-EPMC7484928 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Moderate or Severe Impairment in Pulmonary Function is Associated with Mortality in Sarcoidosis Patients Infected with SARS‑CoV‑2.

Morgenthau Adam S AS Levin Matthew A MA Freeman Robert R Reich David L DL Klang Eyal E

Lung 20200911 5

<h4>Purpose</h4>To investigate whether sarcoidosis patients infected with SARS-CoV-2 are at risk for adverse disease outcomes.<h4>Study design and methods</h4>This retrospective study was conducted in five hospitals within the Mount Sinai Health System during March 1, 2020 to July 29, 2020. All patients diagnosed with COVID-19 were included in the study. We identified sarcoidosis patients who met diagnostic criteria for sarcoidosis according to accepted guidelines. An adverse disease outcome was ...[more]

PMID: 32915271

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Project description:Newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has caused extensive mortality and morbidity and wreaked havoc on socioeconomic structures. The urgent need to better understand SARS-CoV-2 biology and enable continued development of effective countermeasures is aided by the production of laboratory tools that facilitate SARS-CoV-2 research. We previously created a directly accessible SARS-CoV-2 toolkit containing user-friendly reverse genetic (RG) infectious clones of SARS-CoV-2. Here, using K18-human ACE2 (hACE2) mice, we confirmed the validity of RG-rescued SARS-CoV-2 viruses to reproduce the infection profile, clinical disease, and pathogenesis already established in mice infected with natural SARS-CoV-2 isolates, often patient derived. RG-rescued SARS-CoV-2-infected K18-hACE2 mice developed substantial clinical disease and weight loss by day 6 postinfection. RG-rescued SARS-CoV-2 was recovered from the lungs and brains of infected K18-hACE2 mice, and infection resulted in viral pneumonia with considerable changes in lung pathology, as seen previously with natural SARS-CoV-2 infection. In mice infected with RG-rescued SARS-CoV-2-mCherry, mCherry was detected in areas of lung consolidation and colocalized with clinically relevant SARS-CoV-2-assocated immunopathology. RG-rescued SARS-CoV-2 viruses successfully recapitulated many of the features of severe COVID-19 associated with the K18-hACE2 model of SARS-CoV-2 infection. With utility in vivo, the RG-rescued SARS-CoV-2 viruses will be valuable resources to advance numerous areas of SARS-CoV-2 basic research and COVID-19 vaccine development.IMPORTANCE To develop COVID-19 countermeasures, powerful research tools are essential. We produced a SARS-COV-2 reverse genetic (RG) infectious clone toolkit that will benefit a variety of investigations. In this study, we further prove the toolkit's value by demonstrating the in vivo utility of RG-rescued SARS-CoV-2 isolates. RG-rescued SARS-CoV-2 isolates reproduce disease signs and pathology characteristic of the K18-hACE2 mouse model of severe COVID-19 in infected mice. Having been validated as a model of severe COVID-19 previously using only natural SARS-CoV-2 isolated from patients, this is the first investigation of RG-rescued SARS-CoV-2 viruses in K18-hACE2 mice. The RG-rescued SARS-CoV-2 viruses will facilitate basic understanding of SARS-CoV-2 and the preclinical development of COVID-19 therapeutics.

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Moderate or Severe Impairment in Pulmonary Function is Associated with Mortality in Sarcoidosis Patients Infected with SARS?CoV?2.

Publications

Moderate or Severe Impairment in Pulmonary Function is Associated with Mortality in Sarcoidosis Patients Infected with SARS‑CoV‑2.

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