Possible Involvement of Central Nervous System in COVID-19 and Sequence Variability of SARS-CoV-2 Revealed in Autopsy Tissue Samples: A Case Report

Abstract

The case presented here illustrates that interdisciplinary teamwork can be essential for the understanding of the COVID-19 disease presentation and enlightening of the pathophysiology. A 60-year-old woman without any comorbidities, apart from overweight, was found dead in her apartment after 14 days of home isolation due to suspicion of COVID-19. A forensic autopsy was performed. This revealed severely condensed, almost airless, firm lungs, and the cause of death was severe acute respiratory distress syndrome-associated with COVID-19 (SARS-CoV-2). In addition, SARS-CoV-2 was detected with reverse transcription polymerase chain reaction (RT-PCR) in cerebrospinal fluid, lung tissue, and tracheal sample and specific antibodies for SARS-CoV-2 were detected in cerebrospinal fluid and serum. Subsequent sequencing of the SARS-CoV-2 virus showed variation in nucleotides at 3 sites between SARS-CoV-2 isolates recovered from the tracheal sample, cerebrospinal fluid, and tissues from both lungs, and phylogenetic analysis revealed that the spinal fluid sample differed the most from the other 3 samples. This case supports the hypothesis that SARS-CoV-2 may be neuroinvasive and cause central nervous system infection.

Keywords: COVID-19; SARS-CoV-2; complete autopsy; neuroinvasion; whole-genome sequencing.

Figure 1.

(A) Axial postmortem computer tomography scan of the consolidated lungs with peripheral ground glass opacities (solid arrows) and ‘crazy paving’ indicating oedema of the interstium (open arrow). (B) Axial postmortem computer tomography scan of the consolidated lungs with air entrapment (solid arrows) and “crazy paving,” indicating oedema of the interstitium (open arrow). Microscopic pulmonary findings of diffuse alveolar damage showing a spectrum of acute exudative lesions (C-D) to a more consolidated phase with proliferation and organization (E), including a thrombus in the vasculature (F, arrow) (Hematoxylin and eosin staining, 200×). Microscopic immune-histochemical findings showing the deposition of C4d complement fraction in the alveolar structures (G) and microvasculature (H) (IHC for C4d stain; 200×).

Figure 2.

Phylogenetic analysis of patient sequences. Phylogenetic tree rooted with the Wuhan-Hu-1 sequence (NC_045512) and GISAID sequences, shown for example EPI ISL 420347 (GISAID identifier) A2 (Nextstrain clade) and the 4 patient sequences (spinal, tracheal, right lung, and left lung).