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Long COVID leaves patients and researchers in a maze of questions

Millions of COVID-19 survivors worldwide — even those who had mild illness — are reporting long-term symptoms months later, including brain fog, persistent exhaustion, and lung, heart or kidney damage.

Why it matters: For too long, these long-haulers, as they call themselves, have not been taken seriously enough by providers and researchers, some doctors tell Axios, adding that there's an urgent need for dedicated research in order to treat patients with lingering symptoms.


Doctors started to realize long COVID was a problem last spring, and yet "there's little to show for it," says cardiologist Eric Topol, founder and director of Scripps Research Translational Institute

"I'm very disheartened about how poor the attention has been to this. We have at least 10% of people with COVID infections who are suffering, for either a few months or still [now] six months later. ... This is the biggest category of people who are adversely affected, so many of whom can't work and can't function as they normally have."
Eric Topol

What's happening: Many providers and health care systems initially dismissed the symptoms as related to something else, but growing evidence points to SARS-CoV-2 as the culprit in many cases.

  • A study published in The Lancet looked at people who had severe COVID-19 illness in China and found that six months later, 75% continued to experience at least one symptom.
  • A preprint study in medRxiv, not yet peer reviewed, surveyed 3,762 self-described long-haulers from 56 countries, with symptoms after the onset of what was likely COVID-19. Six months after first becoming sick, almost half were unable to work full time and 22% weren't working at all. 88% had cognitive dysfunctions or memory loss, and most had multiple symptoms.
  • Fragments of SARS-CoV-2 have been found in multiple organs and the Mayo Clinic reports they've seen frequent complaints of long-term persistent headaches, loss of smell (anosmia) and taste (ageusia), and trouble sleeping.
  • Mayo found some patients had organ damage, including injured heart muscle, causing myocarditis, palpitations and fast heartbeats; scarred lung tissue, leading to breathing problems; and neurological damage, causing brain fog, strokes, seizures and Guillain-Barre syndrome.

Between the lines: There are other viruses that either cause long-lasting symptoms, such as Epstein-Barr, or stay in the system where it can reactivate and trigger later complications, like varicella-zoster.

  • It is unknown if SARS-CoV-2 can hide in the system, but a recent, early study of animals in the journal Viruses indicates this could be a possibility.
  • The cause of long COVID needs to be discovered before targeted therapies can be made, says Neha Dangayach, director of neuroemergencies management and transfers for the Mount Sinai Health System.
  • "Is it a reactivation of the virus? Is it an immunological response or a persistent immunological response to the initial viral exposure? Or is it a recirculation of the viral particles that trigger some of these symptoms?" Dangayach asks.

There are also many questions about why some people develop long COVID-19 and others don't.

  • "Why you, and not me? Why do [some] 80-year-old people who get COVID die, and some survive? Why do some 20-year-old people who get COVID need a double lung transplant, whereas 90% of all the others have no symptoms? We don't know," says Igor Koralnik, chief of neuro-infectious diseases and global neurology at Northwestern Memorial Hospital, who started a long COVID clinic in May.
  • Topol says they need to figure out whether early treatments like monoclonal antibodies may help diminish the chance of long COVID.

What's next: Long COVID is becoming a higher priority, and several longitudinal studies are expected to come out soon, Dangayach says.

  • In the U.S., Congress has set aside some funding for research and NIH has started studying the issue, NIH director Francis Collins says.
  • Long-haulers are urged to seek specialized clinics, join support networks and consider sharing data in this patient-led survey.
  • While there aren't enough overall,there are a growing number of multidisciplinary clinics popping up around the country to try to address the myriad problems associated with long COVID.
  • Koralnik says his clinic "has specialists in all those different specialities, including psychiatry and social work," to care for long COVID patients.

The bottom line: "The onus really is on us to collaborate across the world and understand this better, develop targeted treatments, and follow these patients longitudinally to also identify when do these symptoms resolve, and what does it take for these symptoms to resolve," Dangayach says.

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