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Secondary Infections May Increase Morbidity and Mortality in COVID-19 Patients

The FLARE Four

  • Viral, bacterial and fungal co-infections have been reported in patients with COVID-19
  • The secondary infections may be a consequence of COVID-19 viral pneumonia, but also from prolonged hospital exposure and critical illness
  • Limited data indicate that nosocomial infections are associated with increased COVID-19 severity and a higher risk of death
  • Risk factors for secondary bacterial and fungal nosocomial infections in patients with COVID-19 include indwelling catheters, diabetes, combination antibiotic therapy and corticosteroid therapy
  • Many of the pathogenic organisms reported in patients with COVID-19 are hospital-acquired, multidrug-resistant organisms, so clinicians should have a low threshold to obtain culture data and start targeted antibiotic therapy

In the 1918, 1957 and 1968 influenza pandemics, and the 2009 outbreak of H1N1 influenza, bacterial co-infection was a significant driver of mortality and morbidity. A fast literature update posted on April 27, 2020, discusses whether the clinical syndrome following SARS-CoV-2 infection might be partly attributable to secondary infection with other pathogens.

The piece is courtesy of Alison Castle, MD, an infectious disease fellow, and the FLARE team with advisory review by Emily Hyle, MD, and Sarah Turbett, MD, physicians in the Infectious Disease Division, and Alyssa Letourneau, MD, MPH, medical director, Antimicrobial Stewardship Program at Massachusetts General Hospital.

Incidence of Co-infection

In one report from the San Francisco Bay area, 20% of 116 non-hospitalized COVID-19 patients were PCR-positive for another respiratory viral pathogen. In contrast, another study from the same region at the same time found no co-infections with influenza or respiratory syncytial virus among 166 hospitalized patients. The authors propose the discrepancy in this data may be due to asymptomatic SARS-CoV-2 infection, such that the positive tests in the non-hospitalized cohort may present incidental findings rather than drivers of upper respiratory illness.

Among 918 hospitalized COVID-19 patients in Wuhan, 7.1% had bacterial or fungal co-infection. Another Wuhan study documented bacterial infection in 43% of 339 COVID-19 patients over the age of 60 who were severely or critically ill.

Organisms Involved

Many of the secondary infections reported in patients with COVID-19 are caused by drug-resistant, hospital-acquired organisms including Pseudomonas aeruginosa, extended-spectrum beta-lactamase–producing Klebsiella pneumoniae, multidrug-resistant Escherichia coli, Acinetobacter and Enterococcus.

Nosocomial Infection

Given the long ICU stays associated with COVID-19, the incidence of secondary infections probably reflects nosocomial infection at least in part. Limited data indicate that nosocomial infections are associated with increased COVID-19 severity and a higher risk of death.

Significant predictors of bacterial and fungal nosocomial infections in COVID-19 are:

  • Indwelling catheters
  • Diabetes
  • Combination antibiotic therapy
  • Corticosteroid therapy

In a single-center study of COVID-19 patients with nosocomial infection, 75% of patients were receiving prophylactic antibiotics. This is evidence against providing empiric prophylaxis, especially since it might select for drug-resistant pathogens.

Massachusetts General Hospital recommends a low threshold to obtain culture data in COVID-19 patients and start targeted antibiotic therapy when appropriate.

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Learn more about the Infectious Disease Division at Mass General

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