How to Treat Covid-19 Lung Scarring

Photo: Virojt Changyencham/Getty Images

One of the scariest elements of Covid-19 is that even among those who survive the disease, damage to the lungs can linger afterward, and it’s unclear whether that tissue will fully recover with time. The destruction caused by the virus that causes Covid-19 can be so severe that in some cases patients require a lung transplant to survive.

At the root of this potentially devastating scarring is a cellular process called fibrosis. That phenomenon occurs when cells produce collagen protein in response to injury, which clogs up tissue. It can occur anywhere in the body, and is even part of the normal healing process when, for example, a person accidentally trips and scrapes their knee. But with Covid-19, the body’s fibrosis reaction might go overboard. “It is very concerning because we haven’t seen this degree of fibrosis in any other disease in the past, even with the original SARS,” says Sachin Chaudhary, MD, director of the Interstitial Lung Disease Program at the University of Arizona College of Medicine.

“Personally I am seeing quite a lot of fibrosis post Covid, and the emerging data are quite a concern,” says Gisli Jenkins, MD, PhD, a lung airway expert at the University of Nottingham. One study published this month showed 65% of Covid-19 patients discharged from hospital had some evidence of lung damage in scans three months later, but the prognosis is not certain. “It’s unknown if it will resolve and get better over time, stay the same, or in the worst-case scenario, turn into something like idiopathic pulmonary fibrosis,” a disease of unknown cause in which lung scarring gets worse and worse with time, Jenkins adds. “If even a small proportion progresses, then given the numbers of patients with Covid then there will be a big problem.”

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Steve Jones knows firsthand the seriousness of unchecked fibrosis in the lungs. He was diagnosed with idiopathic pulmonary fibrosis in 2008. “I could no longer go hiking in the hills and even walking up slight ramps, like you have in shopping malls, became a real challenge,” Jones recalls. He says that daily living tasks such as showering and dressing became more and more difficult. Eventually, he needed supplementary oxygen to walk around the house. “I would have died from respiratory failure but I was really lucky to be accepted for a lung transplant in 2016,” says Jones, who is now president of the European Pulmonary Fibrosis Federation, which represents 21 patient organizations.

There is recent evidence that the SARS-CoV-2 virus, which causes Covid-19, can damage the lining of the little air sacs in the lungs known as alveoli. If the body responds with fibrosis, the collagen that fills these parts of the organ might make it difficult for the body to absorb oxygen. Moreover, Jones says that putting people on a ventilator can also damage the lungs and result in fibrosis in some cases.

“Personally I am seeing quite a lot of fibrosis post Covid, and the emerging data are quite a concern.”

A study published in late November examined the lung tissue from people with Covid-19 who required lung transplants and found remarkable similarities to end stage pulmonary fibrosis — including how messy and disordered the collagen structures were that hold the tissue together. The genetic signatures of the cells in these tissue samples from people with Covid-19 also “mapped almost perfectly onto those from patients with end stage pulmonary fibrosis requiring transplant,” says Scott Budinger, MD, chief of pulmonary and critical care medicine at the Northwestern University Feinberg School of Medicine and one of the study’s authors.

To treat or not to treat

In recent years, the U.S. Food and Drug Administration approved two drugs to treat lung fibrosis. These two drugs, nintedanib and pirfenidone, were both originally developed as anticancer drugs. They can stop or slow the progression of scarring in conditions such as idiopathic pulmonary fibrosis. Unfortunately, however, they cannot reverse the damage. There’s been a continued search to find better treatments for lung fibrosis. (Oddly, even a chemically modified version of the antimalarial drug hydroxychloroquine — which failed in treating Covid-19 after a massive amount of hype — has been tested in rats as a possible treatment for lung fibrosis.)

Nintedanib and pirfenidone are already in clinical trials involving Covid-19 patients, although no results have been reported yet. But Chaudhary cautions against the idea of treating a large number of Covid-19 patients prophylactically with these medications: Not only do they carry side effects, such as bleeding, they are also very expensive, costing around $100,000 a year.

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Chaudhary also stresses that viral infections of the lung often only cause temporary fibrosis that resolves with time. One 2005 study of people infected with the original SARS virus found that a year after their illness, there was some mostly mild scarring in about a third of individuals. Chaudhary says it’s far more likely for experts to see lasting fibrosis in people due to chronic environmental exposures, such as the lasting lung damage observed in coal miners. This is akin to what happens with a chronic injury such as scraping your knee every day in the same place: The healing process starts to go haywire after chronic injury, leaving you with a scar. A similar process happens in the lung with repeated injury.

Also, some researchers have seen low rates of fibrosis in Covid-19. Emanuela Barisione, MD, of the IRCCS San Martino Polyclinic Hospital, says that among the Covid-19 patients her team is studying around 5% had fibrosis at three months.

Yet given the large numbers of people infected with SARS-CoV-2, there’s still a lot of pressure to find drugs that might help treat or prevent scarring. Other drugs currently under study to see whether they might stem fibrosis in Covid-19 include the antibody drug pamrevlumab, which inhibits a protein in the body that encourages the growth of connective tissue. The anti-inflammatory drug colchicine, which is being assessed in a clinical trial of Covid-19 patients, also has theoretical potential to stop fibrosis.

“A plethora of drugs are being tested in patients with severe Covid-19,” Budinger says. He notes that some of these may reduce fibrosis by limiting the severity of the initial injury caused by the virus or by directly targeting the immune system’s role in producing fibrosis. (There’s even renewed hope that by better understanding the cells known as fibroblasts — which secrete collagen and drive scarring — it might be able to one day have drugs that undo tissue scarring.)

But Budinger worries that the studies looking at current drugs’ effects on Covid-19 might take too short a view on outcome, especially for something like fibrosis, which may only manifest as chronic or worsening over a longer period: “Because most of these trials focus on survival alone, I am concerned we might miss a beneficial signal for some of these agents in Covid-19 survivors.”

If the benefits of drugs on fibrosis are to be known then survivors of Covid-19 have to be followed and assessed long after they overcome the SARS-CoV-2 infection. No organ is as hard-hit by Covid-19 as the lungs, and so doctors say that it’s crucial to keep an eye on Covid-19 patients’ lung function far into the future.