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.

Chloroquine- and Hydroxychloroquine-Induced Cardiomyopathy: A Case Report and Brief Literature Review.

OBJECTIVES: To present an index case and review the histologic and electron microscopic findings in chloroquine (CQ) and hydroxychloroquine (HCQ) myopathy, focusing primarily on cardiomyopathy. CQ and HCQ are antimalarial drugs with disease-modifying activity in rheumatic diseases (DMARD) and now are among the most widely used DMARDs. Although they are rare, severe adverse effects caused mainly by deposition of intracellular metabolites in both cardiac and skeletal muscle have been described. Currently, both CQ and HCQ have been proposed to have efficacy for patients with coronavirus disease 2019, and several large centers in the United States and other countries have started clinical trials. METHODS: A case of HCQ cardiotoxicity diagnosed on an endomyocardial biopsy is presented. A review of the pathology archives was performed to identify additional cases of CQ or HCQ myopathy, and histologic changes were recorded. A brief literature review with an emphasis on pathologic findings in myopathies was performed. RESULTS: Including the index case, 4 cases of CQ or HCQ myopathy were identified. Light microscopic findings included vacuolated myopathy, and electron microscopic findings included myeloid bodies and curvilinear inclusion bodies. CONCLUSION: CQ and HCQ myopathy can present following long-term administration of the drug. The pathologic findings are nonspecific and overlap with other vacuolated myopathies, necessitating careful correlation of the histologic changes with the patient's medical history.

A Descriptive and Quantitative Immunohistochemical Study Demonstrating a Spectrum of Platelet Recruitment Patterns Across Pulmonary Infections Including COVID-19.

OBJECTIVES: Pulmonary platelet deposition and microangiopathy are increasingly recognized components of coronavirus disease 2019 (COVID-19) infection. Thrombosis is a known component of sepsis and disseminated intravascular coagulation. We sought to compare the level of platelet deposition in the pulmonary vasculature in cases of confirmed COVID-19 infection to other lung injuries and infections. METHODS: Immunohistochemistry was performed on 27 autopsy cases and 2 surgical pathology cases targeting CD61. Multiple cases of normal lung, diffuse alveolar damage, COVID-19, influenza, and bacterial and fungal infections, as well as one case of pulmonary emboli, were included. The levels of CD61 staining were compared quantitatively in the autopsy cases, and patterns of staining were described. RESULTS: Nearly all specimens exhibited an increase in CD61 staining relative to control lung tissue. The area of CD61 staining in COVID-19 infection was higher than influenza but still comparable to many other infectious diseases. Cases of aspiration pneumonia, Staphylococcus aureus infection, and blastomycosis exhibited the highest levels of CD61 staining. CONCLUSIONS: Platelet deposition is a phenomenon common to many pulmonary insults. A spectrum of staining patterns was observed, suggestive of pathogen-specific mechanisms of platelet deposition. Further study into the mechanisms driving platelet deposition in pulmonary injuries and infections is warranted.