Preeminent COVID-19 scientists urge action to confront Long COVID

A perspective piece on Long COVID by Ziyad Al-Aly and Eric Topol was published in Science magazine today. It reviews the scientific community’s current knowledge about the disorder, as well as remaining gaps in knowledge that are critical to address. It concludes with policy recommendations for how society should move forward in studying, preventing and treating Long COVID.

The authors are preeminent scholars and experts on Long COVID. Dr Al-Aly is a physician-scientist at Washington University in St. Louis. He has numerous high impact publications on COVID-19 and Long COVID and recently testified to Congress at a hearing devoted to the disorder. Among other important pieces, he has led studies on the dangers of COVID-19 reinfections, the effects of Long COVID after more than two years, and comparing the effects of COVID-19 and influenza. 

Dr. Al-Aly [Photo: Dr. Al-Aly]

Dr. Topol is a scientist and executive vice president for research at the Scripps Institute. He was the senior author on a key review article on Long COVID published in Nature Reviews Microbiology. He wrote a critical piece in Science early in the pandemic detailing the impacts of COVID-19 on the heart. 

These scientists start their perspective by summarizing what is known. The disorder affects every organ system and is frequently debilitating. Millions of people have Long COVID. Indeed, other scientists estimate 400 million people worldwide are afflicted. It affects people of all age groups, sex and genetic composition. 

Eric Topol [Photo by Juhan Sonin / CC BY 4.0]

As the authors note, “Long Covid will have wide-reaching effects that are yet to be fully appreciated.”

Risk factors include severe infection and reinfection with the virus. Although severe COVID-19 is associated with a higher risk of developing Long COVID, mild or even asymptomatic SARS-CoV-2 virus infections can cause Long COVID. Each reinfection increases risk.

Several hypotheses for the etiology of Long COVID have been put forward and for which there is growing evidence. They include persistent reservoirs of the virus, viral-induced mitochondrial dysfunction, immune dysregulation including autoimmune disorders, inflammation of blood vessel and neural tissues, and disruptions to the microbiome.

Potential pathophysiological mechanisms implicated in the manifestation of acute and ‘long-COVID’ manifestations in the central nervous system (CNS) [Photo: “Neurological manifestations of long-COVID syndrome: a narrative review”]

In addition to avoiding SARS-CoV-2 infection in the first place, Long COVID can be prevented by vaccines and medications. Vaccines reduce the risk by 15-75 percent. The antiviral combination of ritonavir and nirmatrelvir (branded as Paxlovid) reduces the risk by 26 percent. One randomized controlled trial of the diabetes drug metformin found it reduced the risk by 41 percent.

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