Identification of a protein expression signature distinguishing early from organising diffuse alveolar damage in COVID-19 patients. (preprint)

Diffuse alveolar damage (DAD) is a histopathological finding associated with severe viral infections, including SARS-CoV-2. However, the mechanisms mediating progression of DAD are poorly understood. Applying protein digital spatial profiling to lung tissue obtained from a cohort of 27 COVID-19 autopsy cases from the UK, we identified a protein signature (ARG1, CD127, GZMB, IDO1, Ki67, phospho-PRAS40 (T246), and VISTA that distinguishes early / exudative DAD from late / organising DAD with good predictive accuracy. These proteins warrant further investigation as potential immunotherapeutic targets to modulate DAD progression and improve patient outcome.

No evidence of coronaviruses or other potentially zoonotic viruses in Sunda pangolins (Manis javanica) entering the wildlife trade via Malaysia. (preprint)

The legal and illegal trade in wildlife for food, medicine and other products is a globally significant threat to biodiversity that is also responsible for the emergence of pathogens that threaten human and livestock health and our global economy. Trade in wildlife likely played a role in the origin of COVID-19, and viruses closely related to SARS-CoV-2 have been identified in bats and pangolins, both traded widely. To investigate the possible role of pangolins as a source of potential zoonoses, we collected throat and rectal swabs from 334 Sunda pangolins (Manis javanica) confiscated in Peninsular Malaysia and Sabah between August 2009 and March 2019. Total nucleic acid was extracted for viral molecular screening using conventional PCR protocols used to routinely identify known and novel viruses in extensive prior sampling (>50,000 mammals). No sample yielded a positive PCR result for any of the targeted viral families - Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae and Paramyxoviridae. In light of recent reports of coronaviruses including a SARS-CoV-2 related virus in Sunda pangolins in China, the lack of any coronavirus detection in our upstream market chain samples suggests that these detections in downstream animals more plausibly reflect exposure to infected humans, wildlife or other animals within the wildlife trade network. While confirmatory serologic studies are needed, it is likely that Sunda pangolins are incidental hosts of coronaviruses. Our findings further support the importance of ending the trade in wildlife globally.