Unlocking Spatial Molecular & Cellular Relationships of SARS-CoV-2 in Archived Human Tissue

The true prevalence of SARS-CoV-2 infection in the UK population remains unknown. Phylogenetic diversity estimates derived from genomic sequence tracking algorithms suggest possible arrival of viral strains in the UK several weeks earlier than the first confirmed cases. Diagnostic pathological specimens have continued to be recovered from patients throughout the Covid-19 pandemic, as part of standard investigation and workup across the normal range of clinical indications. Given the symptomatic heterogeneity and probable high rate of asymptomatic infections, we hypothesise that tissue biopsies have already been taken from living patients with clinically unrecognised SARS-CoV-2-infections. Here, we describe the protocol for a retrospective cohort study with the aims of i) detecting SARS-CoV-2 using qRT-PCR in archived biopsy tissue recovered from patients over the course of the pandemic to date, ii) demonstrating qualitative and quantitative evidence of SARS-CoV-2 tissue tropism and cellular-molecular patterns of infection using histological, in situ hybridisation and immunohistochemical techniques, and iii) linking those spatial molecular-cellular characteristics of SARS-CoV-2 infection to clinico-pathologic parameters. The results will provide new insights into the tissue tropism and rates of asymptomatic and ‘atypical’ SARS-CoV-2 infections - information that could immediately impact healthcare practices or public health policy.