Dying of VOC-202012/01 - multimodal investigations in a death case of the SARS-CoV-2 variant

Abstract

The current pandemic with Severe acute respiratory syndrome-coronavirus-2 has been taking on new dynamics since the emergence of new variants last fall, some of them spreading more rapidly. Many countries currently find themselves in a race to ramp up vaccination strategies that have been initiated and a possible third wave of the pandemic from new variants, such as the Variant of Concern-202012/01 from the B.1.1.7 lineage. Until today, many investigations in death cases of Coronavirus-disease-19 have been conducted, revealing pulmonary damage to be the predominant feature of the disease. Thereby, different degrees of macroscopic and microscopic lung damage have been reported, most of them resembling an Acute Respiratory Distress Syndrome. Far more, systemic complications of the disease such as pulmonary embolisms have been described. However, neither morphologic nor virologic findings of patients dying of the new variants have yet been reported. Here, we report on a comprehensive analysis of radiologic, morphologic, and virologic findings in a fatal case of this variant.

Keywords: 501Y.V1; B.1.1.7; Coronavirus-disease-19; Postmortem; Respiratory infections; SARS-CoV-2; Variant of Concern-202012/01.

Fig. 1

Macroscopic findings during the autopsy. An overview of the chest cavity (a) and more detailed pictures of the surface and cross-sections of the lungs (b–d) illustrating bilateral deep red hyperemic discolorations with peripheral hyper-inflation of the lungs. Exemplary deep venous thromboses of the femoral vein are illustrated (e)

Fig. 2

Microscopic findings of the histologic examination. The lungs of the deceased showed signs of diffuse alveolar damage with hyaline membranes (a), hemorrhagic interstitial and alveolar infiltration (b), the presence of microthrombi (c), and an intra-alveolar oedema (d) (H.&E.). Interstitial accumulation of CD8 positive cells (anti-CD8 antibody) was found in the central areas of both lungs (e). Perivascular astrogliosis (anti-glial fibrillary acidic protein antibody) and mild-to-moderate activation of microglia, with occasional microglial nodules in the frontal cortex (anti-HLA-DR antibody) (f–g). Picture specific scale bars are shown

Fig. 3

SARS-CoV-2 whole genome sequencing. a The heat map shows the position (nucleotide positions and amino acid, aa, positions are shown below), identity (indicated with a color code for the individual orfs, synonymous aa substitutions are shown in blue, non-synonymous aa substitutions in orange), and frequency (from 0, gray to 100% frequency, dark blue) of variant nucleotide positions detected by SARS-CoV-2 full genome. Variant sequences of the sample p3212_UKE/HPI are given relative to the set of SNPs identified in B.1.1.7 as previously described (https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563). Additional variant positions present in p3212_UKE/HPI are marked with an asterisk. b Phylogenetic analysis of p3212_UKE/HPI sample within the context of B.1.1.7 isolates. Samples were analyzed and visualized within the phylogenetic context by next strain (nextstrain.org) using data available through GISAID (gisaid.org); GISAID identifiers are indicated at the right. Shown are only closely related sequences with 4 nucleotide substitution difference from the sequence p3212_UKE/HPI (in red). Sequences sampled in Germany, Schleswig–Holstein, are shown in green, while sequences from Denmark are in blue

Fig. 4

Distribution of SARS-CoV-2 RNA loads in different tissues and bodily fluids. Real time-quantitative polymerase chain reaction has been performed from separately taken tissues and bodily fluids. Quantified SARS-CoV-2 RNA copy numbers (E-gene) are shown per milliliter and normalized per cell. Viral copy numbers exceeding those of blood are marked in red. This figure was created with BioRender.com