‘There’s no one long Covid’: Experts struggle to make sense of the continuing mystery

long covid treatment
A laboratory technician isolates Covid-19 samples at the Genview Diagnosis lab in Houston.

Robert Gallo apologized for still coughing. The day before President Biden tested positive for Covid-19, the famed HIV researcher said he was still recovering from a Covid infection that had left him unable to walk, put him in the hospital, and made him delusional, he said Wednesday during a roundtable discussion about long Covid.

Presented by the Global Virus Network, a coalition of leading virologists, the two-day virtual conference convened experts across disciplines and around the world to ask and answer questions about what causes long Covid, how to predict who gets it, how to treat it, and just possibly how to prevent it.

No one has the answers, but Gallo, who co-founded the group and is also director of the Institute of Human Virology at the University of Maryland School of Medicine, puts his money on the amount of virus present right from the start. “We have definitive data that vaccine reduces virus, so if we can take that as a conclusion that the amount of virus is critical to predicting the future, you have a great biomarker,” he said. “I don’t think you can wait. I agree with those clinical people who want to go forward right away.”

To a person, scientists expressed eagerness for better studies, better funding, better participation, with urgency bubbling up from specialists in cardiology, neuroscience, epidemiology, pulmonology, and immunology. Yet these are still early days for research into long Covid. Recognized since 2020, its definition is still sometimes debated, although most definitions include symptoms that persist weeks or months after acute infection and include fatigue, headache, shortness of breath, memory problems, GI issues, and joint and muscle pain.

We still need a taxonomy, Yale cardiologist Harlan Krumholz said, to sort people and their myriad symptoms into groups so that scientists with different expertise can speak the same language as they try to better understand what is going wrong.

But when something seems to work, try it, was the consensus. “I don’t think we should wait just to thoroughly understand a mechanism before trying some reasonable interventions, especially if the interventions are low risk,” Krumholz said.

Epidemiologist Sairam Parthasarathy of the University of Arizona College of Medicine – Tucson painted the picture of prevalence, setting it at 43% of all Covid cases based on pooled evidence of 50 studies. He called out the risk of long Covid as greater than the risk of developing diabetes and asthma, citing a study from Italy that estimated it at 25%. And in the U.S., disadvantaged populations, including Native American and Hispanic people, are disproportionately more likely to be hospitalized for Covid. “It’s a few that may actually carry the burden of the many, and we need to address this,” Parthasarathy said.

There are lessons from another familiar disease: cancer. Michelle Monje, a neuroscientist and neuro-oncologist from Stanford, has previously connected long Covid effects in the brain to the cognitive impairment called “chemo brain” that follows treatment with methotrexate. Now she says long Covid also resembles what happens in the cytokine storm that follows the cancer immunotherapy CAR-T. In all three cases, inflammation disrupts immune cells in the brain called microglia, which ordinarily maintain healthy neural circuit function but when inflammation strikes, become neurotoxic. In mice, she found that depleting microglia with a small molecule that targets a necessary growth factor receptor allows microglia to come back to normal and rescue the cognitive deficits after cancer therapies. “This is something that we have not yet tested, but are in the process of testing in the context of long Covid,” she said.

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