No abstract

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, COVID-19, is an emergent cause of mortality worldwide. Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of COVID-19 individuals undergoing postmortem evaluation is provided, with four aims: 1) describe the pathologic spectrum of the myocardium; 2) compare to an alternate viral illness; 3) investigate angiotensin converting enzyme 2 (ACE2) expression; and 4) provide the first description of the cardiac findings in patients with cleared infection. Methods: Study cases were identified from institutional files and included COVID-19 (n=15; 12 active, 3 cleared), influenza A/B (n=6), and non-virally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An ACE2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction (ddPCR). Results: Male sex was more common in the COVID-19 group (p=0.05). Non-occlusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls), and were more common in the active COVID-19 cohort (p=0.006). Four active COVID-19 cases showed focal myocarditis, while one case of cleared COVID-19 showed extensive disease. Arteriolar ACE2 endothelial expression was lower in COVID-19 cases versus controls (p=0.004). ACE2 myocardial expression did not differ by disease category, sex, age or number of patient comorbidities (p=0.69, p=1.00, p=0.46, p=0.65, respectively). SARS-CoV-2 immunohistochemistry showed non-specific staining, while ultrastructural examination and ddPCR were negative for viral presence. Four (26.7%) COVID-19 patients had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations. Conclusions: This detailed histopathologic, immunohistochemical, ultrastructural and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of active and cleared COVID-19 patients, but is usually limited in extent. Histologic features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.

Compared with indices including weight, the simpler height-based ratio (excluding weight and BSA calculations) yields satisfactory results for evaluating the risk of natural complications in patients with TAAA.

Brain imaging studies of patients with COVID-19 show evidence of macro- and micro-hemorrhagic lesions, multifocal white matter hyperintensities, and lesions consistent with posterior reversible leukoencephalopathy. Imaging studies, however, are subject to selection bias and prospective studies are challenging to scale. Here, we evaluated whether serum neurofilament light chain (NFL), a neuroaxonal injury marker, could predict the extent of neuronal damage in a cohort of 142 hospitalized patients with COVID-19. NFL was elevated in the serum of patients with COVID-19 compared to healthy controls, including those without overt neurological manifestations. Higher NFL serum concentrations were associated with worse clinical outcomes. In one hundred hospitalized patients with COVID-19 treated with remdesivir, a trend toward lower NFL serum concentrations was observed. These data suggest that patients with COVID-19 may experience neuroaxonal injury and may be at risk for long-term neurological sequelae. Neuroaxonal injury should be considered as an outcome in acute pharmacotherapeutic trials for COVID-19.