Pathologic Features of Post-Acute Sequelae of COVID-19 (PASC) at Autopsy

ABSTRACT

Background: Across the globe, cases of post-acute sequelae of COVID-19 (PASC) are characterized by the delayed effects of SARS-CoV-2 infection in multiple organ systems. Patients may have appeared to recover from the initial infection, but experience sequelae of the disease weeks to months later. Autopsy studies of PASC have only initially begun. Our research aims to compare the pathology of cases in which patients experienced a prolonged, progressive decline, to the cases of patients who recovered from the initial infection of SARS-CoV-2, but experienced sequelae of the condition numerous weeks to months later. Design: Autopsies were performed on 17 male and female decedents with an age range of 31-79 years with cause of death related to COVID-19 infection confirmed by SARS-CoV-2 PCR, and time between the onset of symptoms and death ranging from 30 to 112 days. Cases in which the time between the onset of symptoms and death exceeded 30 days, with evidence of initial recovery, were considered potentially PASC-related. The cases were separated into two groups based upon the timeline of first positive PCR to time of death those who succumbed to the initial COVID-19 infection after an extended hospital course, and those with potential PASC-related disease. Clinical, gross and microscopic findings from both groups were compared, as well as PCR and IHC for SARS-CoV-2 at autopsy. Results: The most common clinical comorbidity seen in both groups was hypertension (85.7%), followed by obesity and diabetes. Common microscopic findings in the lungs included proliferative to organizing diffuse alveolar damage (DAD). Findings in PASC-related cases included extensive alveolar fibrosis, fibrosing organizing pneumonia, and thrombi within medium-sized blood vessels. Two patients in their 30s presented with vasculitis/endotheliitis involving small blood vessels of the lungs and heart, consistent with Multisystem Inflammatory Syndrome. Additionally, late thrombotic events, and cardiac inflammation including macrophage infiltration appeared to be present in cases of PASC. Immunostaining for SARS-CoV-2 nucleocapsid and PCR at the time of autopsy did not reveal a persistence of virus in cases attributed to PASC. Figure 1 - 7 Conclusions: Our findings suggest that there may be pathologic differences between a prolonged course of acute COVID-19, and PASC-related disease. Characteristics of PASC included evidence of new or continued small vessel inflammation, macrophage infiltration, and/or fibrotic disease of affected organs.