A race to determine what drives COVID-19 severity

Efforts are ongoing to find which human or viral factors underpin whether a person with COVID-19 will develop severe symptoms. Clinical evidence linked to two viral lineages now provides key insights into this enigma.

The coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS‑CoV-2) emerged in late 2019, and certain aspects of the disease it causes — COVID‑19 — continue to baffle clinicians and researchers. It is estimated that SARS-CoV-2 has already infected more than 9 million people and claimed more than 450,000 lives worldwide, and this pandemic has paralysed economies globally. Writing in Nature, Zhang et al. present data on the evolution of two major lineages of SARS-CoV-2, together with information regarding human-host determinants of disease severity from their analysis of 326 people in Shanghai, China, who were infected with SARS-CoV-2.

SARS-CoV-2, which caught the world by surprise, was initially thought to have ‘jumped’ to humans from an animal host at the Huanan Seafood Wholesale Market in Wuhan, China. When the first cases of a previously unknown disease, initially described as ‘a severe pneumonia with unknown aetiology’, were identified in Wuhan at the end of December 2019, the majority of cases could be traced back to this market.

The implication was that the new coronavirus had crossed the species barrier at the market from an infected live animal on sale. The Malayan pangolin, a scaly anteater previously living in relative obscurity, suddenly faced allegations that it was the culprit, although whether this protected creature was on sale in the market at that time is uncertain (see Nature http://doi.org/ggpxhb; 2020). However, some cases of the disease in early December 2019 in Wuhan had no obvious links to the market.

Zhang et al. analysed 94 complete genome sequences of SARS-CoV-2 in samples obtained from people living in Shanghai who had visited a health-care clinic in January or February 2020, and compared these data with 221 other sequences of the virus. The authors’ results reinforce previous observations of two major phylogenetic lineages (clades) of SARS-CoV-2 during the early phase of the outbreak in China. They are distinguished by two distinctive nucleotide differences, suggesting multiple origins for the human infections transmitted to people in Shanghai (which is about 800 kilometres by road from Wuhan).

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