Coinfections in Patients With Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Study

Abstract

Background: The frequency of coinfections and their association with outcomes have not been adequately studied among patients with cancer and coronavirus disease 2019 (COVID-19), a high-risk group for coinfection.

Methods: We included adult (≥18 years) patients with active or prior hematologic or invasive solid malignancies and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection, using data from the COVID-19 and Cancer Consortium (CCC19, NCT04354701). We captured coinfections within ±2 weeks from diagnosis of COVID-19, identified factors cross-sectionally associated with risk of coinfection, and quantified the association of coinfections with 30-day mortality.

Results: Among 8765 patients (hospitalized or not; median age, 65 years; 47.4% male), 16.6% developed coinfections: 12.1% bacterial, 2.1% viral, 0.9% fungal. An additional 6.4% only had clinical diagnosis of a coinfection. The adjusted risk of any coinfection was positively associated with age >50 years, male sex, cardiovascular, pulmonary, and renal comorbidities, diabetes, hematologic malignancy, multiple malignancies, Eastern Cooperative Oncology Group Performance Status, progressing cancer, recent cytotoxic chemotherapy, and baseline corticosteroids; the adjusted risk of superinfection was positively associated with tocilizumab administration. Among hospitalized patients, high neutrophil count and C-reactive protein were positively associated with bacterial coinfection risk, and high or low neutrophil count with fungal coinfection risk. Adjusted mortality rates were significantly higher among patients with bacterial (odds ratio [OR], 1.61; 95% CI, 1.33-1.95) and fungal (OR, 2.20; 95% CI, 1.28-3.76) coinfections.

Conclusions: Viral and fungal coinfections are infrequent among patients with cancer and COVID-19, with the latter associated with very high mortality rates. Clinical and laboratory parameters can be used to guide early empiric antimicrobial therapy, which may improve clinical outcomes.

Keywords: CAPA (COVID-19-associated pulmonary aspergillosis); COVID-19; bacterial infections; mucormycoses; viral infections.

Figure 1.

Descriptive flowchart of patients included in the study. ^aNonmelanoma skin cancers, in situ malignancies, or premalignant conditions. ^bDuplicate records, noninvasive malignancies, precursor or benign hematologic conditions, presumed false-positive SARS-CoV-2 test results, low QS from a non-CCC19 site. Abbreviations: CCC19, COVID-19 and Cancer Consortium; QS, quality score; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

Forest plot of categorical clinical variables significantly associated with at least ≥1 coinfection category (bacterial, viral, or fungal). Recent cytotoxic chemotherapy is that received between 4 weeks and 3 months from the date of COVID-19 diagnosis. Abbreviation: COVID-19, coronavirus disease 2019.

Figure 3.

Thirty-day all-cause mortality by coinfection type. The width of the boxes is proportional to the number of coinfections; the height of the boxes is proportional to the number of patients who died or did not die within 30 days.