Coinfection and superinfection in ICU patients with severe COVID-19- or influenza-related pneumonia: What are the risk factors?

7 December, 2023

COVID-19 and influenza outbreaks increase the risk of critical illness among patients, consequently increasing in the risk of severe bacterial coinfections and superinfections,¹ the latter of which commonly occur during the recovery phase.^2–8As of March 2023, we have yet to identify the specific risk factors for coinfections and superinfections in concurrent COVID-19 and influenza cases.

A recent retrospective study from China aimed to address this knowledge gap. The study analysed demographic data, clinical data and microbiological examination results from severe COVID-19 (n=123) and influenza (n=145) patients admitted to the ICU. The study sought to describe the prevalence, pathogenic distribution and clinical aspects of coinfections and ICU-acquired superinfections in patients with COVID-19 and influenza, and additionally, identify independent risk factors at the time of ICU admission through univariate and multivariate analyses.⁹

Key findings included:

In the COVID-19 cohort, coinfections and ICU-acquired superinfections occurred in 41 (33.3%) and 54 (43.9%) of cases, respectively.⁹

In patients with COVID-19 that experienced coinfections,⁹
- Enterococcus faecium (7.9%), Pseudomonas aeruginosa (7.3%) and Acinetobacter baumannii (4.9%) were the prevalent bacteria.
- Aspergillus and Candida spp. played a significant role in subsequent fungal infection, contributing to 17.9% and 5.7% cases of fungal infection, respectively.
- Approximately 16.6% of cases of bacterial coinfection involved multidrug-resistant (MDR) organisms.
In patients with COVID-19 that experienced ICU-acquired superinfections,⁹
- baumannii (22%) emerged as the predominant bacteria, followed by C. striatum (18.7%), Klebsiella pneumoniae (6.5%), Escherichia coli (4.1%) and E. faecium (4.1%).
- A substantial 59.6% of patients exhibited infections involving MDR bacteria.
- Fungal infections were predominantly owing to Aspergillus (13%), Candida spp. (4.1%) and Rhizopus spp. (1.6%).
- Human cytomegalovirus (CMV) infection was detected in 4.9% of patients.

In the influenza cohort, the incidence of coinfections and superinfections was 51 (35.2%) and 76 (52.4%), respectively.⁹

In patients with influenza that experienced coinfections,⁹
- aureus (3.4%) emerged as the predominant Gram-positive bacteria.
- The primary Gram-negative bacteria identified were baumannii (9.7%), P. aeruginosa (6.9%), and K. pneumoniae (4.1%).
- Fungal infections were mainly attributed to Aspergillus (12.4%), followed by Candida spp. (2.1%) and Rhizopus spp. (0.7%).
- CMV (6.2%) was the most prevalent virus.
In patients with influenza that experienced ICU-acquired superinfections,⁹
- Common bacteria included baumannii (28.3%), P. aeruginosa (21.4%), K. pneumoniae (11.7%) and Burkholderia cenocepacia (11.7%).
- The prevalence of aeruginosa, Stenotrophomonas maltophilia, and B. cenocepacia among patient with influenza was significantly higher compared with the COVID-19 group (21.4% vs 3.3%, p<0.001; 7.6% vs 0.8%, p=0.008; 11.7% vs 2.4%, p=0.004, respectively).
- The influenza group had fewer Corynebacterium striatum infections than the COVID-19 group (2.1% vs 18.7%, p<0.001).
- MDR bacteria were present in 60.2% of patients, similar to the proportion observed in the COVID-19 group.
- Notable contributors to fungal infections were Candida (5.5%), Aspergillus spp. (4.1%), and Pneumocystis jirovecii (0.7%). The influenza group had a lower incidence of Aspergillus spp. infection compared to the COVID-19 group (4.1% vs. 13%, p=0.008).
- ICU-acquired CMV infection was observed in 11.7% of cases.

Evaluation of the risk factors for coinfections/ICU-acquired superinfections at ICU admission revealed distinctive factors for both groups:⁹

In patients with COVID-19, the risk factors for coinfections included an Acute Physiology And Chronic Health Evaluation (APACHE) II score of ≥18 [Odds ratio (OR): 2.309; 95% confidence interval (CI): 1.005–5.304; p=0.049], CD8+ T cell count ≤90/μL (OR: 2.466; 95%CI: 1.084–5.612; p=0.031), and patient age of 50 to 70 years old (OR: 2.680; 95%CI: 1.183–6.072; p=0.018).
For ICU-acquired superinfections in patients with COVID-19, risk factors included CD8+ T cells count ≤90/μL (OR: 6.016; 95% CI: 2.270–15.944; p<0.001), C-reactive protein (CRP) level ≥120 mg/L (OR: 4.111; 95%CI: 1.508–11.208; p=0.006), IL-8 level ≥20 pg./mL (OR: 3.178; 95% CI: 1.233–8.192; p=0.017), blood glucose level ≥10 mmol/L (OR: 2.843; 95% CI: 1.101–7.341; p=0.031), hypertension (OR: 2.694; 95%CI: 1.041–6.973; p=0.041) and smoking (OR: 4.599; 95% CI: 1.723–12.275; p=0.002).
In patients with influenza, independent predictive variables for coinfections included body mass index (BMI) ≤23.5 kg/m² (OR: 2.722; 95% CI: 1.304–5.683; p=0.008) and white blood cell (WBC) count ≥10 × 10⁹/L (OR: 2.102; 95% CI: 1.009–4.380; p=0.047).
WBC ≥10 × 10⁹/L (OR: 2.419; 95% CI: 1.175–4.983; p=0.017), fever (OR: 0.263; 95% CI: 0.084–0.826; p=0.022), expectoration (OR: 0.328; 95% CI: 0.129–0.835; p=0.019) and dyspnoea (OR 4.190; 95% CI: 1.229–14.291; p=0.022) were factors associated with a higher rate of ICU-acquired superinfections in patients with influenza.

Key findings with respect to the influence of coinfections and ICU-acquired superinfections on treatment and prognosis included:⁹

Patients with coinfections in severe COVID-19 pneumonia had higher use of antifungal agents, incidence of acute kidney injury, need for tracheal intubation, tracheotomy, extracorporeal membrane oxygenation and prone position compared to those without coinfections. This patient group also had a significantly longer duration of intensive positive-pressure ventilation.
Among the influenza cohort, treatment and outcomes were similar between patients with and without coinfections.
Patients with ICU-acquired superinfections in both the COVID-19 and influenza groups had higher rates of tracheal intubation, length of intensive positive-pressure ventilation and length of ICU stay compared with patients without ICU-acquired superinfections.
In the COVID-19 group, patients with ICU-acquired superinfections had higher rates of acute kidney injury, cardiovascular failure, gastrointestinal bleeding, continuous renal replacement therapy, tracheotomy and need for prone position and recruitment, compared with patients without ICU-acquired superinfections. The hospital survival rate was lower for patients with ICU-acquired superinfections compared with patients without ICU-acquired superinfections in the COVID-19 group.
ICU-acquired superinfection, corticosteroid administration for COVID-19 treatment before ICU admission and Sequential Organ Failure Assessment (SOFA) score ≥7 were independent prognostic factors.

In conclusion, the study revealed that coinfections and ICU-acquired superinfections are prevalent among both ICU-admitted COVID-19 and influenza patients, emphasising a need for close monitoring and timely, targeted antibiotic treatments for those at high risk of infections.⁹ Given that there are distinct pathogens identified as most frequently responsible for coinfections in ICU patients, tailored empirical antibiotic choice, based on pathogen identification and susceptibility testing, is critical.

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