Protean manifestations of COVID-19: “Our ignorance is profound”


‘Make sure that they didn’t die in vain’

There was interest in those and other reports on Consult, and comments from physicians who have theories, but no certain answers about what is, and is not, caused by the virus.

Direct viral attack is likely a part of it, said Stanley Perlman, MD, PhD, a professor of microbiology and immunology at the University of Iowa, Iowa City.

The ACE2 receptor the virus uses to enter cells is common in many organs, plus there were extrapulmonary manifestations with severe acute respiratory syndrome (SARS), another pandemic caused by a zoonotic coronavirus almost 20 years ago. At least with SARS, “many organs were infected when examined at autopsy,” he said.

Dr. William Shaffner

Dr. William Shaffner

The body’s inflammatory response is almost certainly also in play. Progressive derangements in inflammatory markers – C-reactive protein, D-dimer, ferritin – correlate with worse prognosis, and “the cytokine storm that occurs in these patients can lead to a degree of encephalopathy, myocarditis, liver impairment, and kidney impairment; multiorgan dysfunction, in other words,” said William Shaffner, MD, a professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center, Nashville, Tenn.

But in some cases, the virus might simply be a bystander to an unrelated disease process; in others, the experimental treatments being used might cause problems. Indeed, cardiology groups recently warned of torsade de pointes – a dangerously abnormal heart rhythm – with hydroxychloroquine and azithromycin.

“We think it’s some combination,” but don’t really know, Dr. Krumholz said. In the meantime, “we are forced to treat patients by instinct and first principles,” and long-term sequelae are unknown. “We don’t want to be in this position for long.”

To that end, he said, “this is the time for us all to hold hands and be together because we need to learn rapidly from each other. Our job is both to care for the people in front of us and make sure that they didn’t die in vain, that the experience they had is funneled into a larger set of data to make sure the next person is better off.”


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