COVID-19, caused by the SARS-CoV-2 virus, has resulted in over 6.8 million deaths worldwide.¹ Risk factors associated with severe COVID-19 disease symptoms include advanced age, male sex and comorbidities.² Although initial reports indicated that bacterial co-infection had limited impact on overall severity and mortality of COVID-19 infection, a recent multicenter, retrospective cohort study published in Critical Care challenges this notion.³

In this study, Patton and colleagues analysed data from 13,781 adult COVID-19 inpatients across two institutions (University of Alabama at Birmingham [UAB, n=4,075] and Ochsner Louisiana State University Health Shreveport [OLSH, n=9,706]) between 2020 to 2022 to determine the impact of community-acquired bacterial co-infection on COVID-19 clinical outcomes.³ In this study, bacterial co-infection was defined as the presence of a pathogenic isolate from blood cultures taken 48 hours after hospital admission.³

Based on blood cultures, investigators divided patient cases into three groups: (1) confirmed bacterial co-infection (recovery of bacterial pathogen, 2.5%), (2) suspected bacterial co-infection (negative culture with two or more antimicrobials administered, 46%), or (3) no evidence of bacterial co-infection (no culture, 51.5%).³

Multivariate logistic regressions were used to assess the risk factors for COVID-19 bacterial co-infection, as well as the impact of co-infection on mortality, intensive care unit (ICU) admission and mechanical ventilation.³

The key findings of the study include³:

• Compared with other risk factors linked to COVID-19, including a history of diabetes and renal disease, community-acquired bacterial co-infection was a significant risk factor for severe outcomes, including in-hospital mortality (UAB: odds ratio [OR], 3.07; 95% confidence interval (CI), 2.42–5.46; OLHS: OR, 4.05; 95% CI, 2.29–6.97; p<0.001 for both), ICU admission (UAB: OR, 4.47; 95% CI, 2.87–7.09; OLHS: OR, 2.65; 95% CI, 2.00–3.48; p<0.001 for both), and mechanical ventilation (UAB: OR, 3.84; 95% CI, 2.21–6.12; OLHS: OR, 2.75; 95% CI, 1.87–3.92; p<0.001 for both).
• Mortality associated with COVID-19 bacterial co-infection (24%) was four times higher than the mortality associated with community-acquired bacteremia in pre-COVID-19 pandemic inpatients (5.9%).
• An elevated neutrophil-to-lymphocyte ratio (NLR) of at least 15 within 48 hours of hospital admission was associated with an increased likelihood of COVID-19 bacterial co-infection (UAB: OR, 1.95; 95% CI, 1.21–3.07; p<0.0001; OLHS: OR, 3.65; 95% CI, 2.66–5.05; p<0.0001).
• Three systemic inflammatory response syndrome (SIRS) criteria, including heart rate above 90 beats per minute (UAB: OR, 1.52; 95% CI, 1.02–2.40; p=0.052; OLHS: OR, 1.81; 95% CI, 1.25–2.83; p=0.003), body temperature below 36°C or above 38°C (UAB: OR, 2.14; 95% CI, 1.37–3.22; p=0.001; OLHS: OR, 1.62; 95% CI, 1.24–2.13; p=0.001), and white blood cell counts below 4 or above 12 × 10³/µL (UAB: OR, 3.01; 95% CI, 1.94–4.48; p<0.0001; OLHS: OR, 3.34; 95% CI, 2.55–4.57; p<0.0001) were significantly associated with increased likelihood of COVID-19 bacterial co-infection.
• Dexamethasone-induced neutrophilia did not affect the observation of elevated NLR in confirmed COVID-19 bacterial co-infection.
• Other biomarkers, such as elevated lactate and creatinine levels, as well as elevated C-reactive protein and procalcitonin, were also associated with co-infection.
• Regardless of the timing of SARS-CoV-2 variant waves, COVID-19 bacterial co-infection significantly increased the likelihood for in-hospital mortality (alpha: OR, 4.12; 95% CI, 2.71– 6.04; p<0.001; delta: OR, 3.23; 95% CI, 1.65–5.74; p<0.001; omicron: OR, 5.49; 95% CI, 1.98–13.8; p<0.001).

In conclusion, the study revealed that community-acquired bacterial co-infection is a significant risk factor for severe outcomes, including in-hospital mortality, ICU admission, and mechanical ventilation.³ The findings also suggested that elevated NLR and components of the SIRS could play a crucial role as early and unambiguous prognostic biomarkers for COVID-19 bacterial co-infections.³ Overall, the study highlights a need for early identification and clinical intervention of bacterial co-infection in COVID-19 patients, to optimise clinical outcomes.

References

1. World Health Organization. Citing websites: Weekly epidemiological update on COVID-19 – 6 April 2023. Emergency Situational Updates, 2023; 137. Available from: https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19—6-april-2023. Accessed on 5 May 2023.
2. Dessie ZG and Zewotir T. BMC Infect Dis 2021;21:855.
3. Patton MJ, et al. Crit Care 2023;27:34.