Invasive aspergillosis superinfection should be considered in critically ill patients with SARS-CoV-2 infection with worsening disease, according to research published in Open Forum Infectious Diseases.

Accounting for over 5 million cases to date of coronavirus disease 2019 (COVID-19), SARS-CoV-2 has rapidly spread across the globe. COVID-19 includes a wide spectrum of illness that ranges from asymptomatic or mild infection to critical illness with acute respiratory distress syndrome (ARDS). It is estimated that 20% of patients who develop symptomatic COVID-19 may go on to develop ARDS. In patients with COVID-19-associated ARDS, the mortality rate is high, and recovery can be complicated by arrhythmia, cardiac injury, shock, or superinfections.

Since the 1918 influenza pandemic, physicians have recognized that opportunistic infections can follow viral infections. During the 2009 influenza A (H1N1) outbreak, cases of invasive pulmonary aspergillosis developed in patients with ARDS who did not have classic risk factors for fungal disease. Studies have also observed high rates of invasive pulmonary aspergillosis in patients with influenza complications including respiratory failure. Other respiratory viruses have been shown to predispose patients to invasive pulmonary aspergillosis, including parainfluenza virus and respiratory syncytial virus. While the pathophysiologic mechanisms that are involved and responsible for invasive pulmonary aspergillosis are not completely clear, direct damage to the airway epithelium may provide opportunity for Aspergillus species to invade tissues.

While data on secondary infections that complicate severe COVID-19 is limited, there have been reports of high incidence of secondary infections in critically-ill patients with COVID-19 in the intensive care unit (5%-31%); however, the diagnostic criteria for these reports were not provided. Other studies have also demonstrated prevalence of Aspergillus: one study reported either Aspergillus flavus or Aspergillus fumigatus in 4% of patients with severe SARS-CoV-2 in China, another reported Aspergillus flavus infection in patients with severe SARS-CoV-2 in France, and a third reported on probable aspergillosis diagnoses in 33% of patients who required mechanical ventilation.


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These early findings suggest invasive aspergillosis may be an important but under-recognized complication of SARS-CoV-2 infection.

“If aspergillosis is a complication of COVID-19 in a significant minority of critically ill hospitalized patients, failure to recognize or diagnose the disease will likely lead to excess mortality,” the researchers wrote. Therefore, “it is imperative to establish the incidence, clinical characteristics, and outcomes of COVID-19-associated aspergillosis as quickly as possible.”

To define the incidence and clinical features of COVID-19-related aspergillosis, the most immediate need is for detailed data from large cohorts of patients who presented in the first global wave of cases. A second priority would be to conduct systemic studies of COVID-19-associated pulmonary aspergillosis to identify and employ uniform diagnostic testing and criteria. Autopsy studies on patients infected with SARS-CoV-2 should be conducted to perform microbiologic cultures and tissue staining in the lungs to identify infections, including aspergillosis. Finally, clinical trials should be conducted to determine what prophylactic, pre-emptive, or empiric antifungal therapy should be used.

“[W]e recommend consideration of aspergillosis as a cause of super-infection in COVID-19 patients with worsening clinical or radiographic findings,” the researchers concluded.

Reference

Thompson GR III, Cornely OA, Pappas PG, et al. Invasive aspergillosis as an underrecognized superinfection in COVID-19 [published online June 19, 2020]. Open Forum Infect Dis. doi:10.1093/ofid/ofaa242