Mortality Risk From COVID-19 Among Unvaccinated Subjects With Autoimmune Phenotypes of Interstitial Lung Disease.

BACKGROUND: The impact of the severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) virus on patients with interstitial lung disease (ILD) remains poorly understood. As patients with ILD often have severe underlying lung parenchymal involvement, and immunosuppressive therapy is common in this population, they are presumed to be at high risk for severe coronavirus disease 2019 (COVID-19) pneumonitis. Our aim was to explore demographic and clinical differences between those with ILD who tested positive for the SARS-CoV-2 virus compared to those with ILD who did not. METHODS: In this retrospective cohort study, we identified adult, unvaccinated patients evaluated at the University of Chicago in 2020 who were enrolled in the ILD registry, and stratified by SARS-CoV-2 seropositive status. We then compared baseline clinical characteristics between SARS-CoV-2 seropositive and SARS-CoV-2 seronegative patients and assessed immunosuppressive therapy that the patient may have been on since ILD diagnosis. C-reactive protein and leukocyte subsets were evaluated at COVID diagnosis compared to the time of baseline ILD evaluation as were pulmonary function testing. Variable comparisons were determined by two-sided t-tests or chi-square tests as appropriate, and logistic regression models were fitted to assess the odds of death from COVID-19 using generalized linear models with maximum-likelihood estimation. RESULTS: Of the 309 individuals with ILD in our cohort, 6.8% (n=21) tested positive for SARS-CoV-2. Those who were SARS-CoV-2 positive were younger (57 years vs 66 years; P=0.002), had baseline higher total lung capacity (81% vs 73%, P=0.045), similar forced vital capacity (71% vs. 67%, P=0.37), and similar diffusion capacity of carbon monoxide (71% vs. 62%, P=0.10) at baseline. Among patients with ILD and COVID-19, 67% had received immunosuppressive therapies compared to 74% of those with ILD without COVID-19. Those with ILD and COVID-19 were also more likely to have had a diagnosis of autoimmune-related ILD (connective tissue disease-ILD or interstitial pneumonia with autoimmune features) (62% vs 38%, P=0.029). Overall, the mortality hazard was highest among unvaccinated subjects with autoimmune-related ILD who had COVID-19 (OR=9.6, 95% CI=1.7-54.0; P=0.01). DISCUSSION: SARS-CoV-2 is prevalent in ILD, and may put unvaccinated adults who are younger, with autoimmune ILD, and on immunosuppressive therapy at higher risk. This suggests a need for COVID-19 vaccinations and therapy (inpatient and outpatient) for this group of patients at high risk for COVID-19. Larger studies are needed to fully explore the relationship between ILD and immunosuppressive therapy in COVID-19.

A series of COVID-19 autopsies with clinical and pathologic comparisons to both seasonal and pandemic influenza.

Autopsies of patients who have died from COVID-19 have been crucial in delineating patterns of injury associated with SARS-CoV-2 infection. Despite their utility, comprehensive autopsy studies are somewhat lacking relative to the global burden of disease, and very few comprehensive studies contextualize the findings to other fatal viral infections. We developed a novel autopsy protocol in order to perform postmortem examinations on victims of COVID-19 and herein describe detailed clinical information, gross findings, and histologic features observed in the first 16 complete COVID-19 autopsies. We also critically evaluated the role of ancillary studies used to establish a diagnosis of COVID-19 at autopsy, including immunohistochemistry (IHC), in situ hybridization (ISH), and electron microscopy (EM). IHC and ISH targeting SARS-CoV-2 were comparable in terms of the location and number of infected cells in lung tissue; however, nonspecific staining of bacteria was seen occasionally with IHC. EM was unrevealing in blindly sampled tissues. We then compared the clinical and histologic features present in this series to six archival cases of fatal seasonal influenza and six archival cases of pandemic influenza from the fourth wave of the 'Spanish Flu' in the winter of 1920. In addition to routine histology, the inflammatory infiltrates in the lungs of COVID-19 and seasonal influenza victims were compared using quantitative IHC. Our results demonstrate that the clinical and histologic features of COVID-19 are similar to those seen in fatal cases of influenza, and the two diseases tend to overlap histologically. There was no significant difference in the composition of the inflammatory infiltrate in COVID-19 and influenza at sites of acute lung injury at the time of autopsy. Our study underscores the relatively nonspecific clinical features and pathologic changes shared between severe cases of COVID-19 and influenza, while also providing important caveats to ancillary methods of viral detection.