When failure to correct a flawed paper could put patients’ lives at risk

Robert Speth

On April 15, 2021, as COVID-19 was waning several months prior to the surge in deaths associated with arrival of the Delta variant, the journal Cell published an eye-catching paper. 

Titled “Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system,” the article stood in stark contrast to the contemporary understanding of the mechanism of SARS-CoV-2 infection, which until then held that ACE2 on the membranes of susceptible cells served as the “receptor” for the virus.

The paper was notable because it claimed that vasopressin, also known as antidiuretic hormone, worsened COVID-19 infections. Vasopressin is known for its ability to promote water retention in the kidneys as well as to constrict blood vessels, but had not previously been associated with COVID-19 infections. 

Upon reading the paper, one of us (MB) noted a large number of inaccuracies. The authors had used the wrong reagent: a high molecular weight precursor of vasopressin rather than vasopressin itself. They also incorrectly portrayed ACE2, the V1B vasopressin receptor, and the AT1 angiotensin II receptor – the primary mediators of their hypothetical mechanism of COVID-19 infection. (PubPeer commenters also pointed out problems in the paper, including a failure of the authors to post their original data.)

Continue reading When failure to correct a flawed paper could put patients’ lives at risk