Pulmonary aspergillosis in US Veterans with COVID-19: a nationwide, retrospective cohort study

Abstract

Background: COVID-associated pulmonary aspergillosis (CAPA) was described early in the pandemic as a complication of SARS-CoV-2. Data about incidence of aspergillosis and characteristics of affected patients after mid-2021 are limited.

Methods: A retrospective, nationwide cohort of US Veterans with SARS-CoV-2 from 1/1/2020 to 2/7/2024 was created. Potential cases of aspergillosis ≤12 weeks of a SARS-CoV-2 test were flagged electronically (based on testing results indicative of invasive fungal infection, antifungal therapy, and/or ICD-10 codes), followed by manual review to establish the clinical diagnosis of pulmonary aspergillosis. Incidence rates were calculated per 10,000 SARS-CoV-2 cases. Selected clinical characteristics included age >70, receipt of immune-compromising drugs, hematologic malignancy, chronic respiratory disease, vaccination status, and vaccine era. Multivariate logistic regression was used to estimate the independent effects of these variables via adjusted odds ratios (aOR).

Results: Among 674,343 Veterans with SARS-CoV-2, 165 were electronically flagged for review. Of these, 66 were judged to be cases of aspergillosis. Incidence proportions ranged from 0.30/10,000 among patients with zero risk factors to 34/10,000 among those with ≥3 risk factors; rates were similar in the pre- and post-vaccination eras. The 90-day mortality among aspergillosis cases was 50%. In the multivariate analysis, immune suppression (aOR 6.47, CI 3.84-10.92), chronic respiratory disease (aOR 3.57, CI 2.10-6.14), and age >70 (aOR 2.78, CI 1.64-4.80) were associated with aspergillosis.

Conclusions: Patients with underlying risk factors for invasive aspergillosis continue to be at some risk despite SARS-CoV-2 immunization. Risk in patients without immune suppression or preexisting lung disease is very low.

Figure 1.

Monthly incidence (total number of cases) of COVID-19 associated pulmonary aspergillosis (CAPA) from March 2020 through March 2024 (top panel) and the monthly incidence of SARS-CoV-2 infection during the same period (bottom panel)—US Department of Veterans Affairs.

Figure 2.

Incidence of clinically significant pulmonary aspergillosis by the number of weeks after the positive test for SARS-CoV-2 (Panel A, only patients with aspergillosis, N = 66), and incidence of death by the number of weeks after the positive test for SARS-CoV-2 among patients with aspergillosis (Panel B) or all patients (Panel C). The data are intended to be descriptive and were not subjected to statistical analysis.

Figure 3.

Incidence of Aspergillosis per 10,000 SARS-CoV-2 Infections, by Number of Risk Factors related to compromised immunity (transplantation, prior treatment with immune-compromising drugs, history of hematologic malignancy) or chronic respiratory disease). * Due to small numbers, 3 and 4 risk factors were combined into one category.