Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients

Abstract

Background: Post-mortem studies can provide important information for understanding new diseases and small autopsy case series have already reported different findings in COVID-19 patients. Methods: We evaluated whether some specific post-mortem features are observed in these patients and if these changes are related to the presence of the virus in different organs. Complete macroscopic and microscopic autopsies were performed on different organs in 17 COVID-19 non-survivors. Presence of SARS-CoV-2 was evaluated with immunohistochemistry (IHC) in lung samples and with real-time reverse-transcription polymerase chain reaction (RT-PCR) test in the lung and other organs. Results: Pulmonary findings revealed early-stage diffuse alveolar damage (DAD) in 15 out of 17 patients and microthrombi in small lung arteries in 11 patients. Late-stage DAD, atypical pneumocytes, and/or acute pneumonia were also observed. Four lung infarcts, two acute myocardial infarctions, and one ischemic enteritis were observed. There was no evidence of myocarditis, hepatitis, or encephalitis. Kidney evaluation revealed the presence of hemosiderin in tubules or pigmented casts in most patients. Spongiosis and vascular congestion were the most frequently encountered brain lesions. No specific SARS-CoV-2 lesions were observed in any organ. IHC revealed positive cells with a heterogeneous distribution in the lungs of 11 of the 17 (65%) patients; RT-PCR yielded a wide distribution of SARS-CoV-2 in different tissues, with 8 patients showing viral presence in all tested organs (i.e., lung, heart, spleen, liver, colon, kidney, and brain). Conclusions: In conclusion, autopsies revealed a great heterogeneity of COVID-19-associated organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs.

Evidence of central nervous system infection and neuroinvasive routes, as well as neurological involvement, in the lethality of SARS‐CoV‐2 infection

“…In the study reported by Solomon et al 46 and the study by Al‐Dalahmah et al, 48 the positive PCR results for SARS‐CoV‐2 in the CNS have not been confirmed in the same brain areas by immunostaining or in situ hybridization. In the study of Remmelink et al, 47 although SARS‐CoV‐2 RNA was found in 9 of 11 cerebral samples, autopsy examination did not found evidence of viral encephalitis or vasculitis. These discrepancies raised the question whether the positive PCR tests were false or not.…”

“…Up to September 14, 2020, a total of 20 autopsy studies on neuropathology were retrieved, among which CNS detection of SARS‐CoV‐2 was negative in 12 (of 12) cases from three studies, 36,42,43 and positive in 58 (of 87) cases (66.7%) from nine studies, 46‐54 and unavailable for 109 cases in eight studies 35,37‐41,44,45 …”

“…On August 12, Remmelink et al 47 carried out a postmortem study on 17 adult patients with COVID‐19, who died from respiratory failure or multiple organ failure. They found eight cases with cerebral hemorrhage or hemorrhagic suffusion, three with focal ischemic necrosis, five with edema and/or vascular congestion, and 10 with diffuse or focal spongiosis.…”

“…Most autopsies provided insufficient details, which may reflect the challenge of studying such patients. As a matter of fact, complete brain removal was difficult or even not allowed in some studies 40,47 . As neurotropic viruses infect only specific brain areas related to their entry routes, incomplete or random sampling is not suitable for the study of CNS infection.…”

Cardiac SARS-CoV-2 infection is associated with distinct transcriptomic changes within the heart

“…In our study, 93% of cases suffered from two or more comorbidities which is coherent with other autopsy studies beyond Hamburg. 28,[42][43][44] Interestingly, neither cardiac nor other comorbidities were associated with cardiac infection and even signs of virus replication in the myocardium were not more frequent in those with comorbidities. This is different in other organs, like the kidney, where cases with organ manifestation in general were more likely to have more comorbidities.…”