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By Mary Carpenter
THE RECEDING Covid pandemic is leaving behind a tsunami of new research that focuses on different individuals’ immune responses to the virus, offering the hope of one day creating personal, immunity-response profiles that could lead to better treatment decisions early on, for Covid and for other infections, such as the flu.
Driving this research are questions about why Covid infections in patients—who are of similar age, background and health status—can follow “wildly different trajectories,” according to NBC News; or why some patients develop long-lasting post-Covid symptoms.
“One thing that was surprising to us was the large percentage of asymptomatic patients that are in that category of long Covid,” said Robin Gelburd, president of the non-profit FAIR Health, which tracked health insurance records of nearly two million Americans.
Also surprising, more than half of patients hospitalized with severe Covid in a Belgian study had “rogue” antibodies, autoantibodies that can disable immune system proteins and attack other organs affected by Covid—which “should make us rethink dozens of diseases, if not hundreds,” according to David Lee at New York University Langone Health. “I’m like, ‘How is anybody not seeing this?’”
This “autoimmunity might be the real culprit behind deadly destruction that continues after the coronavirus has cleared,” said Lee. According to the Nature report, “scientists are very interested in whether autoimmunity is linked to long Covid.”
Although women with Covid infections have less severe symptoms and fewer deaths, they experience long-haul problems at more than four times the rate of men. (Women are also more likely to have autoimmune diseases, such as lupus, MS and rheumatoid arthritis.) On the other hand, the international Covid Human Genetic Effort study of patients with life-threatening Covid pneumonia found dangerous auto-antibodies in only 2.6% of women but in 12.5% of men, for whom they may be the cause of the more severe infections and higher numbers of deaths.
Other reasons for the severity of Covid in men could be that obesity poses a greater risk to men who have the infection; or that testosterone puts men at greater risk—or women’s estrogen levels help protect them.
Important Covid-immunity research comes from so-called “supertasters”–people who have a strong response to bitterness, for example, in coffee and broccoli, and who appear practically immune to Covid infection. In past research, the “supertaster gene” TaR38 has correlated with a stronger immune response to bacterial infections in the sinus and lungs.
Taste strips assessing individual levels of bitterness response were close to 95% accurate in predicting the risk of infection, severe disease and need for hospitalization —in a recent study of 1,935 people exposed to Covid but with no evidence of infection, by ENT researchers in Baton Rouge and at UC San Diego. While more research is needed, taste-strip tests could provide a simple contribution to personal immunity profiles.
Other unusual responders to Covid include those who develop severe infections but produce no antibodies at all. About one-third of 9,785 severe Covid patients in the UK’s large Recovery trial failed to produce any antibodies in response to coronavirus infection—in some cases, because underlying health conditions had weakened their immune systems; but in others, for no clear reason.
In the Recovery research, among patients who received a new cocktail of two genetically engineered monoclonal antibodies, 24% died, compared with 30% of those who received standard care. The Regeneron cocktail is the same as the one given to former President Trump, explained Scripps Research Translational Institute Director Eric Topol. “Who knows what might have happened at his age, with his morbid obesity and all the other risk factors he had” without the cocktail.
At a different extreme of the immunity spectrum are the patients who produce autoantibodies, which, in addition to blocking immune function, attack organs—blood vessels, heart and brain —and phospholipids that affect blood clotting, all of which can be affected by Covid. Most hospitalized Covid patients have neurological symptoms.
While many people have a few rogue antibodies— perhaps due to genetic predisposition—the first evidence that autoantibodies against the body’s immune system might put people at higher risk of infectious disease came in 1984, said Rockefeller University researcher Jean-Laurent Casanova. With the Covid pandemic, now “people understand the problem.”
Down the road, creating personal immunity profiles could help with treatment decisions, such as whether to supply missing antibodies to bolster a patient’s immune system or to protect a patient against the creation of rogue autoantibodies—or to determine which patients should be hospitalized and which ones can just go home.
Finally, but still not well understood are the long-haul Covid symptoms, which affect around one-fourth of all Covid patients—hundreds of thousands of Americans, including children and those with mild or asymptomatic Covid— and can last for months following coronavirus infection. In addition to brain fog and intense fatigue, lasting symptoms can include parosmia and phantosmia—distortions in the senses of smell and taste.
Some observers speculate that Covid’s severe toll on men may help lead to better attention for its symptoms—including for the enduring brain fog and fatigue, even though these affect more women than men—than has occurred for other infections, notably Lyme disease. In common with Covid, Lyme has early non-specific flu-like symptoms, as well as the post-infectious fatigue and brain fog.
In general, Covid has put Lyme disease and its enduring effects under a new spotlight—after years of little attention as well as funding. In a loose comparison, the government has so far authorized $3.7 trillion for all Coronavirus support vs. $14 million in FY 2020 for Lyme and other tick-borne diseases, but dedicated entirely to prevention and control.
For me, Lyme disease is the reason that, despite knowing that those who are fully vaccinated against Covid have a very small risk of being infected and that they should expect only a mild or even asymptomatic course of disease, I remain cautious about Covid exposure from unvaccinated people.
Since the acute infection in 2008, peripheral neuropathy in my legs and feet can interfere with walking and balance, and my cholesterol levels have remained more than 100 points higher than previously. When my knee doctor recently said it was time for replacement, he blamed Lyme-related arthritis for hastening the deterioration.
But the doctor was also very cheerful about the declining Covid statistics, as well as about the possibility that his office will dispense with mask requirements on July 1.
—For the past year Mary Carpenter has been closely following the trajectory of Covid-19 .