Coccidioidomycosis and COVID-19 Co-Infection, United States, 2020

Alexandra K. Heaney; Jennifer R. Head; Kelly Broen; Karen Click; John Taylor; John R. Balmes; Jon Zelner; Justin V. Remais

Disclosures

Emerging Infectious Diseases. 2021;27(5):1266-1273. 

In This Article

Risk Factors for Severe Disease

Although most cases of coccidioidomycosis or COVID-19 are mild respiratory illnesses, either infection can cause severe disease and death (Appendix). Risk factors associated with severe coccidioidomycosis or COVID-19 often overlap, prompting concerns of elevated death rates associated with co-infections or serial infections. Patients with SARS-CoV-2 and Coccidioides co-infection might be at higher risk for severe disease; however, whether synergistic effects might exist requires further data. Overlapping risk factors associated with severe disease caused by coccidioidomycosis or COVID-19 include older age, diabetes mellitus, immunosuppression, Black/African American ancestry, and smoking (Appendix references 56–70). Although the long-term pulmonary effects of COVID-19 remain unknown, early data suggest that the virus might cause lung damage (Appendix reference 71), resulting in elevated long-term risk for severe coccidioidomycosis.

Age

Older persons have heightened risk for severe disease caused by either infection. In the United States, 62% of COVID-19 hospitalizations and 80% of deaths were among patients >65 years of age (Appendix reference 72). Similarly, older persons, especially those >65 years of age, with coccidioidomycosis have higher risk for severe pulmonary disease. Rates of coccidioidomycosis-associated death increase with age. These trends might be partially explained by the higher prevalence among older adults of preexisting conditions and immunosuppression, which are risk factors for severe COVID-19 and coccidioidomycosis (Appendix references 56–64).

Diabetes

Diabetes is also associated with severe progression of either disease (Appendix references 56,63–68). A study of COVID-19 patients found that those with diabetes had a higher risk for severe pneumonia and organ damage (Appendix reference 73). The study also showed that patients with diabetes were more susceptible to a SARS-CoV-2–induced cytokine storm, which can cause rapid deterioration and death (Appendix reference 73). In addition, patients with diabetes are more likely to have relapsing coccidioidomycosis (risk ratio [RR] 3.39, 95% CI 1.65–6.46) or cavitary lung disease (RR 2.94, 95% CI 1.63–4.90) than those without diabetes (Appendix reference 74). Furthermore, among coccidioidomycosis patients with diabetes, those with higher serum glucose levels are more likely to have disseminated coccidioidomycosis, the most severe form of the disease, than those with lower levels (Appendix reference 74). The exact mechanisms through which diabetes influences the progression of coccidioidomycosis and COVID-19 are not well understood but might be related to impaired innate and adaptive cellular immunity (especially T-cell function) or the effects of a hyperglycemic environment on microorganism virulence (Appendix references 75).

Immunosuppression

Although immunosuppressive steroids such as dexamethasone have reduced inflammatory lung damage in patients with severe COVID-19 (Appendix reference 76), emerging evidence suggests that persons with a history of prolonged immunosuppression might be at higher risk for severe COVID-19. A study of 17 million adults in the United Kingdom found higher risks for death among COVID-19 patients who have hematologic malignancies, who are taking immunosuppressant drugs for organ transplants, or who have other causes of immunosuppression (Appendix reference 77). Immunosuppressed patients with cancer or solid organ transplants might be at higher risk for severe COVID-19 (Appendix reference 78). Coccidioidomycosis patients with suppressed immune responses, such as patients with hematologic malignancies, HIV, or organ transplants, also have higher risk for disseminated disease (Appendix references 61–63).

Black/African American Ancestry

Black persons have higher rates of severe COVID-19 and disseminated coccidioidomycosis than do White persons. Growing evidence indicates higher risk for severe COVID-19–associated disease and death among Black than White persons living in the United States (Appendix). A study of coccidioidomycosis in military personnel found dissemination rates to be 10 times higher among Black than White persons (Appendix reference 79). Similarly, a study in Kern County, California, found that patients with disseminated coccidioidomycosis were 4.6 times more likely to be Black than patients with mild disease (Appendix reference 56). The observed racial and ethnic disparities in severe COVID-19 and coccidioidomycosis are probably driven by structural inequities that systematically disadvantage persons of color in the forms of reduced healthcare access and exposure to environmental stressors that increase risk for conditions such as diabetes, obesity, and hypertension, which are associated with severe disease.[29] For coccidioidomycosis, whether any biological basis for this association exists is unclear but might be related to immunogenic differences in T-cell function (Appendix references 56,69,70).

Smoking

Recent history of cigarette smoking has been linked to higher risk for severe disease from either infection. A systematic review and meta-analysis found that smokers with COVID-19 were significantly more likely (RR 2.4, 95% CI 1.43–4.04) to be admitted to an intensive care unit, need mechanical ventilation, or die compared with nonsmokers (Appendix reference 80). A case–control study in Kern County found that patients with severe or disseminated coccidioidomycosis were more likely to have smoked cigarettes in the previous 6 months compared with patients with mild coccidioidomycosis (Appendix reference 56).

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