COVID-19 brings thousands of people into hospitals every day—but their coronavirus infections are not always the direct reason they die. Dangerous secondary infections by opportunistic pathogens are common in intensive care units, and physicians are raising the alarm about a particular microbial threat to COVID-19 patients: a common fungus known as Aspergillus.
Emerging evidence suggests that infection with SARS-CoV-2—and possibly the drugs used to treat it—makes COVID-19 patients especially vulnerable to Aspergillus. The threat, which also surfaced during the 2009 flu pandemic, is leading some researchers to urge more careful fungal surveillance of the sickest COVID-19 patients and treatment with antifungal drugs.
Aspergillus “is ubiquitous—you can’t avoid it,” says George Thompson, an infectious disease physician at the University of California, Davis. Members of its genus produce spores that can float in the air, and “we breathe in hundreds to thousands or more [of them] per day,” he says.
Those spores normally don’t harm us. Aspergillus infections were typically considered a threat only to immunocompromised patients, such as those undergoing cancer treatments or bone marrow transplants. But in 2009, doctors saw a spike in previously healthy people who succumbed to Aspergillus. They had all first become sick with a new, pandemic strain of the influenza virus H1N1.
For reasons scientists still don’t completely understand, influenza infections appear to make the fungus more deadly in people with a seemingly normal immune system. In a 2016 review of 57 cases of Aspergillus infections in influenza patients reported since 1963, Nancy Crum-Cianflone, an infectious disease specialist at Scripps Mercy Hospital, found that about half of the co-infected patients died.
Now, something similar may be happening with COVID-19. Just as H1N1 was a severe strain of influenza, the SARS-CoV-2 virus is an especially dangerous form of coronavirus, Crum-Cianflone says. That could help explain why it leaves COVID-19 patients vulnerable to new threats.
Data on Aspergillus infections in people with COVID-19 are still sparse, but case reports point to worrying trends. One study from Germany found that one-quarter of critically ill COVID-19 patients also had Aspergillus infections. Another study of COVID-19 patients on ventilators found probable Aspergillus in one-third of them.
It’s not uncommon for COVID-19 patients to be infected with other harmful microbes. But Aspergillus may be the deadliest threat among them, says Adilia Warris, a medical mycologist at the University of Exeter. She points to a recent study of 186 COVID-19 patients from around the world who also had Aspergillus. It found that slightly more than 50% of them died, and roughly one-third of those deaths were linked to Aspergillus infections.
Thompson estimates that anywhere between 2% and 10% of severely ill COVID-19 patients at his hospital also have an Aspergillus infection. “It’s obviously a minority of patients,” he says. “But the complications of a secondary infection are generally pretty substantial.”
Doctors say there are a few reasons why having COVID-19 might be an especially strong risk factor for an Aspergillus infection. One is that while COVID-19 can send parts of the immune system into overdrive, it also depletes certain immune cells, leaving a patient less able to fight off other infections. The extreme damage to cells lining the lung also impairs the organ’s ability to clear out respiratory pathogens like Aspergillus, Thompson says.
The way physicians treat COVID-19 could also heighten the risk of an Aspergillus infection. The steroid dexamethasone, shown to improve survival rates among severely ill COVID-19 patients, calms an overactive immune response that can lead to dangerous inflammation and organ damage. But immunosuppressive steroids are a double-edged sword, Crum-Cianflone says, leaving the door open to other infections. A recent observational study of four COVID-19 patients with likely Aspergillus infections noted that three of them had received higher steroid doses than was recommended—all of them died.
If doctors could easily identify Aspergillus infections, available antifungal drugs could fight them. But because the fungus can cause nonspecific symptoms such as coughing and shortness of breath that are already common in COVID-19 patients, doctors don’t always look for it. A bronchoscopy, in which doctors snake a tube from the nose or mouth into the lungs, is the best way of taking lung samples for analysis. But the procedure isn’t typically done on COVID-19 patients for fear of spreading viral particles. And even a positive test may not mean the fungus is doing damage; Aspergillus can also be present in the lungs as a harmless colonizer.
As a preventive measure, Crum-Cianflone has begun giving severely ill COVID-19 patients antifungal drugs after their third week of hospitalization, even if they haven’t tested positive for Aspergillus. But even that strategy has risks. Overusing these compounds could lead to drug-resistant strains of Aspergillus becoming more common, Warris notes.
Recently, in The Lancet, an international group of physicians and medical mycology societies laid out recommendations for diagnosing Aspergillus infections in COVID-19 patients, including doing lung imaging scans and taking samples from the lungs at regular interval for testing. The hope is that the guidelines will help COVID-19 doctors know whether they’re battling one deadly pathogen, or two.