How Covid Sends Some Bodies to War With Themselves

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The idea of manipulating the immune system as a way to fight Covid-19 first arose last winter in China after physicians there observed that greater inflammation seemed to correlate with worse outcomes. In March, some Italian doctors turned to immune-modulating drugs as well, says Marco Gattorno, head of the Center for Autoinflammatory Diseases and Immunodeficiencies at the Giannina Gaslini Institute in Genoa. So many intubated patients were dying, he told me, that physicians felt they had to try something to lower mortality rates. “They were rather desperate, because they realized that indeed it was a grave problem,” he says, referring to his colleagues on the front lines. “We were able to convince the people not to be too shy with glucocorticoids” — that is, steroids. And the death rate among I.C.U. patients at his hospital who received immune-modulating drugs seemed to decline.

It’s probably no coincidence that those who have been most forcefully advocating to try Covid-19 therapies that rein in the immune system are often rheumatologists. Their specialty makes them quite familiar with the vagaries of the immune system and the drugs used to try to control it. But their willingness to use immune-modulating drugs in this pandemic without supporting evidence from robust studies is sometimes frowned upon by other specialists, many of whom worry about the consequences of deliberately weakening immune defenses while an infection is raging.

This proposed fix is something of a paradox. It posits that the best way to help some patients survive Covid-19 may not be to fortify the immune system, so that it can fight the virus with greater ferocity, but to subtly suppress the counterattack, so that the patient avoids self-destruction. The notion is controversial, not least because differentiating an appropriate immune response from a self-harming one can be difficult. An added wrinkle is the fact that SARS-CoV-2, the virus that causes Covid-19, may itself stifle aspects of the immune response, meaning that additional immune suppression could make things worse.

Each new study further complicates the picture of what exactly is going wrong with the immune system in severe Covid-19 cases. But the evidence continues to mount indicating that something is going awry, immunologically speaking. And in the absence of a vaccine, figuring out the best way to correct this dysfunction may prove crucial to helping patients survive the disease.

This might be the case even if a course of treatment includes antiviral medicines. In a recently published preliminary report involving remdesivir, for example, some Covid-19 patients who received that antiviral drug experienced accelerated recovery times — remdesivir seemed to help, in other words. But the drug did not significantly lessen overall mortality rates. The very sick still died. One reason for this lack of improvement, according to Chaz Langelier, an infectious-disease specialist at the University of California, San Francisco, might be that the immune system, not the virus directly, is driving the disease in these instances. Helping those patients may require calming the immune system....