Rheumatologists Change Covid Treatment



SARS-CoV-2 vaccines that are widely available for the general population could be a ways off, and both testing and contact tracing are still riddled with inefficiencies. As a result, improvements in the treatment of Covid is an important route forward —by reducing the severity of infection and the risk of dying—to make the threat of this coronavirus closer to that of seasonal flu and improve possibilities for reopening.

Seasonal flu, however, caused 61,000 deaths in the severe 2017-2018 season —less than one-third of deaths so far attributed to Covid in the U.S., but a high number.  On the other hand, as winter approaches, worries mount that contracting both flu and Covid at the same time could make each a more serious illness.

Generally for treating Covid, emergency medicine and ICU doctors make decisions based on large, controlled studies —the current gold standard being Britain’s Recovery megatrial that early in the pandemic enrolled some 12,000 patients from National Health Service hospitals.  In late June, Recovery released data from a controlled study of about 6,500 patients showing that treatment with the steroid dexamethasone reduces deaths by one-third for patients on a ventilator.

But beginning steroids at a crucial point in the progression of a Covid infection came first from the opposite end of the research spectrum — small-scale, individualized experiences of rheumatologists, who are experts in out-of-whack immune systems, notably in autoimmune diseases, explains Moises Velasquez-Manoff, whose recent New York Times magazine article explores rheumatologists’ role in revolutionizing Covid treatments.

Early on, rheumatologists focused on the immune overreaction known as a cytokine storm that was drowning the lungs of severely afflicted patients —which, their experience told them,, might be countered by immunosuppressants like steroids. Rheumatologists are also specialists in Covid symptoms afflicting “long-haulers” that are similar to those of Chronic Fatigue Syndrome (CFS), which includes prolonged relapses of exhaustion, cognitive dysfunction and other symptoms after a minimal amount of activity.

Rheumatology originated with the study of rheum —a word derived from phlegm, meaning “substances that flow,” one of the four bodily humors in an ancient system of medicine. Referred to as rheumatic diseases, systemic autoimmune conditions can affect the eyes skin, nervous system and internal organs—and include everything from chronic back pain and tendinitis to more than 100 forms of arthritis.

“The idea of manipulating the immune system as a way to fight Covid,” writes Velasquez-Manoff, first arose in China and soon after with Italian physicians desperate for a way to stop patients from dying.  After a few successes, said Marco Gattorno, head of the Center for Autoinflammatory Diseases and Immunodeficiencies in Genoa, “We were able to convince [doctors] not to be too shy with glucocorticoids (steroids).”

In April, prior experience with rheumatoid arthritis (RA) provided a clue to Cornell Weill rheumatologist Iris Navarro-Millan, who had seen Covid patients declining rapidly, when she was treating a patient in his 60s who struggled to breathe even with nasal tubes and then a mask to dispense oxygen. Navarro-Millan tried the RA drug anakinra (with the patient’s consent). By the following morning, he no longer needed the mask, and a week later he went home.

Because autoimmune diseases are relatively rare, rheumatologists are more accustomed to relying on individual case experiences. “It’s hard to conduct large trials…to study a given drug in, for example, the sliver of lupus patients who develop cytokine storms,” writes Velasquez-Manoff.  “The best evidence sometimes comes from case studies.”

In contrast, critical care doctors treating Covid have tended to rely on large studies of illnesses with symptoms closely related to those of Covid, like ARDS (acute respiratory distress syndrome) from the flu and sepsis, for which immunosuppressants did not work— and focused instead on bolstering the immune reaction fighting the virus.

Individualized treatment is especially important with Covid because of the crucial element of timing: using antivirals like remdesivir at early stages to suppress viral activity, but at a specific point when the virus is beyond control, turning to anti-inflammatories to counter immune system overreaction like the cytokine storm.

Clues to treating Covid come from people who test positive but are asymptomatic. “Their immune systems evidently handle the invasion with the perfect balance of aggression, restraint and repair—or tolerance—to stave off the disease,” explained Salk Institute infectious diseases specialist Janelle Ayres.

But until better tools exist to effectively eliminate the virus from our bodies, physicians have shifted their focus to tweaking the immune system, writes Manoff-Velazquez, “from eradicating the pathogen to helping the patient survive the pathogen.”

And while dexamethasone proved a major advance, it helped only those patients needing a ventilator (36%) or those on supplemental oxygen (18%) —but for less sick patients slightly increased the risk of death.

Among dozens of potential remedies focused on prodding the immune system now being studied, colchicine—used for thousands of years to treat gout, a type of arthritis—has few side effects and exists in pill form. Thus, it’s a simpler option than the more serious cancer drugs and high-tech “biologics,” antibodies manufactured in living cells, that are mostly given intravenously.

Large-scale studies on new treatments, however, may take a while to produce results impressive enough for general use. And even then, rheumatologic expertise may be what helps physicians do the necessary tailoring of treatments for individual patients, considering everything from their pre-existing conditions to crucial timing in the progression of their Covid infection.

For more immediate concerns, get a flu shot—though for sufficiently long-lasting protection, wait until the end of September. For those 65 and older, two vaccine options produce a stronger immune response than the standard dose—with the choice depending on your doctor’s advice: high-dose Fluzone, which contains four times the amount of antigen, and FLUAD which includes an adjuvant for extra boost.  No research has yet compared these two.

And always: wear a mask.


—Mary Carpenter

Well-Being Editor Mary Carpenter is on a mission to keep us updated on Covid-19. To read more of her posts, click here.



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