I Spy an Opportunistic Infection?

COVID-19, caused by SARS-CoV-2 and first detected in late 2019 in Wuhan, China, is known to affect various systems of our body, primarily targeting the lungs. Currently, steroids are essentially the treatment of choice when COVID-19 pneumonia is associated with hypoxia. The use of tocilizumab (Actemra), a humanized monoclonal antibody against the IL-6 receptor, has gained importance due to its efficacy in subduing cytokine storms. However, the associated immunosuppression resulting from these therapeutic agents predisposes patients to opportunistic infections.

Recently, there have been increasing reports of opportunistic infections in patients affected by COVID-19. Infection with “black fungus” is one such opportunistic infection being associated with COVID-19, particularly in Asian countries such as India. The term black fungus is referring to mucormycosis or zygomycosis and is labeled as black due to the discoloration caused by necrosis from angioinvasion of the infected tissues. Mucormycosis, caused by fungi belonging to genera Rhizopus, Mucor, and Rhizomucor, commonly involves nasal sinuses, orbits, and the cerebrum/brain. Pulmonary involvement is not uncommon. The exact prevalence of these opportunistic infections among COVID-19 patients is currently unknown, probably due to their poor recognition.

Oral candidiasis is another opportunistic infection seen in patients with COVID-19 who are on steroids and broad-spectrum antibiotics. Another opportunistic infection reported in some cases of COVID-19 patients admitted to the ICU is invasive pulmonary aspergillosis. A group from Chicago published a case of acute respiratory distress syndrome (ARDS) due to COVID-19 infection who developed large bilateral cavitary lesions consistent with aspergillomas after receiving two doses of tocilizumab. Italian researchers described two cases of people with COVID-19 admitted with ARDS who developed HSV-1 viremia with fulminant hepatitis shortly after initiating tocilizumab leading to their deaths.

The exact mechanisms of opportunistic infections in COVID-19 patients are unclear, but steroids suppresses inflammation associated with COVID-19 pneumonia and tocilizumab is an immunomodulating agent. Patients with underlying comorbidities such as uncontrolled blood sugars, history of malignancies (particularly hematological), organ transplants, and those on chronic immunosuppressive therapy are particularly at risk of opportunistic infections. Fungi causing mucormycosis thrive well in high glucose and acidotic environments. Steroids can worsen a patients’ blood sugar levels and can suppress immunity, putting them at risk of acquiring mucormycosis.

Other types of patients are also at risk of opportunistic infections: those who are critically ill admitted to ICU, patients with ARDS, and those on ventilators, broad-spectrum antibiotics, or total parenteral nutrition. Lower lymphocyte count in critically ill COVID-19 patients is implicated as a risk factor. A team of researchers from Paris described a case of invasive pulmonary aspergillosis in an immunocompetent patient diagnosed with severe COVID-19 infection. Hence, further studies are needed to establish a correlation between these two.

There’s a trend taking shape: opportunistic infections associated with COVID-19 are increasingly reported. On the frontlines of such infections, healthcare providers can play an important role in monitoring for early signs and symptoms.

Healthcare providers need to keep a close eye on patients’ blood sugars when they start taking steroids for COVID-19 pneumonia. Adequate control of these blood sugars can mitigate the risk of mucormycosis. Although difficult, it is also crucial to evaluate patients for underlying bacterial or fungal infection before initiating tocilizumab. Occurrences of certain opportunistic infections such as mucormycosis and invasive pulmonary aspergillosis increase the risk of mortality in COVID-19 patients similar to that seen in SARS and H1N1 influenza. Early diagnosis of these opportunistic infections is necessary; however, this could be challenging due to the overlap of symptoms with the COVID-19 infection itself. Symptoms that are atypical for COVID-19 — such as bloody nasal discharge, hemoptysis, orbital swelling, visual disturbances, or the development of new symptoms and/or worsening of the clinical status of the patients after initiating immunomodulators — should prompt immediate investigations for opportunistic infection to mitigate the risk of mortality in these patients.

Catching such infections early isn’t always easy, but it can go a long way in saving lives.

Shivaraj Nagalli, MD, is a board-certified internal medicine physician working as a hospitalist at Shelby Baptist Medical Center in Alabama.

Last Updated June 07, 2021