A recent study published in the Journal of Infection evaluated clinical differences between critically ill coronavirus disease 2019 (COVID-19) and influenza patients.

Background

The most common cause of acute respiratory failure was influenza before COVID-19. The influenza pandemic has been used for modeling and planning for epidemics. The common features of COVID-19 and influenza are human-to-human transmission through droplets and acute respiratory distress syndrome. Nonetheless, only a few studies have compared the characteristics and outcomes of COVID-19 and influenza patients. 

About the study

In the present study, researchers compared the clinical features and outcomes between COVID-19 patients and a historical influenza cohort in France using data from an administrative healthcare database. COVID-19 patients admitted to intensive care units (ICUs) between March 2020 and June 2021 were included. Besides, patients in the historical influenza cohort were admitted to ICUs between 2014 and 2019.

Patients required appropriate International Classification of Diseases, Tenth Revision (ICD-10) codes for the diagnosis of influenza or COVID-19 for inclusion. Age, sex, and simplified acute physiology score II (SAPS-II) were recorded at admission, and the Charlson comorbidity index was calculated. Patients with medullar aplasia, solid organ transplants, agranulocytosis, or cancer treatment were deemed immunocompromised.

During hospitalization, the team recorded the use of non-invasive (NIV) or invasive ventilation, extracorporeal membrane oxygenation (ECMO), high-flow nasal cannula (HFNC), prone positioning, and vasopressors. Additionally, they documented if patients developed venous thrombosis events or underwent renal replacement therapy.

The study outcomes were ICU/hospital stay, ventilation duration, and vital status at discharge. Vaccination status was obtained beginning in 2021. Chi-squared or Wilcoxon tests were used for comparisons between influenza and COVID-19 patients. The team identified risk factors using the Fine-Gray model. First, they estimated the sub-hazard ratio for invasive ventilation in univariate analysis.

Subsequently, a multivariable analysis was adjusted for a predefined set of confounders such as age, infection type, sex, heart disease, diabetes mellitus, cancer, immunosuppression, modified SAPS-II, hematologic malignancies, arterial hypertension, and chronic kidney disease. The association between infection type and in-hospital death was also determined.

Findings

The study included 105,979 COVID-19 and 18,763 influenza patients. Most COVID-19 patients were males and had lower SAPS-II scores at admission than influenza patients. Diabetes mellitus, solid tumors, arterial hypertension, and chronic kidney disease were more common in the COVID-19 cohort.

In contrast, cirrhosis, malignancies, chronic respiratory diseases, and congestive heart disease were more common in the influenza cohort. Around 34%, 18%, and 6% of COVID-19 patients required invasive ventilation, HFNC, and NIV, respectively. By contrast, most influenza patients (47%) required invasive ventilation.

COVID-19 was associated with a reduced likelihood of invasive ventilation and an increased in-hospital mortality risk without invasive ventilation. Prone positioning was used for 19% and 12% of COVID-19 and influenza patients, respectively, whereas ECMO was used for 1% of patients in each cohort. The COVID-19 cohort was less likely to require vasopressors and renal replacement therapy than the influenza cohort.

COVID-19 patients were more likely to develop pulmonary embolism than influenza patients. In-hospital deaths were more in the COVID-19 cohort than in the influenza cohort. Notably, for patients aged <60, in-hospital deaths were higher among influenza patients than in the COVID-19 cohort. On the contrary, for patients aged 60 or above, mortality was higher in the COVID-19 cohort.

The adjusted Fine-Gray model revealed a higher risk of in-hospital mortality in COVID-19 patients than in influenza patients, particularly for patients aged 65 or older. This finding was consistent among the sub-group of patients requiring invasive ventilation. The hospital stay was longer for COVID-19 patients than for influenza patients. ICU stay was longer for COVID-19 patients, albeit the difference was not relevant clinically.

However, in the subgroup of patients with invasive ventilation, COVID-19 patients had a significantly longer ICU stay than influenza patients. The researchers performed sensitivity analyses restricting COVID-19 patients admitted in 2021 and found that COVID-19 patients had an elevated mortality risk relative to influenza patients, irrespective of the COVID-19 vaccination status.

Conclusions

To summarize, the researchers observed significant differences in ICU management and clinical characteristics and outcomes between critical COVID-19 and influenza patients. COVID-19 patients were less likely to require invasive ventilation. Regardless, COVID-19 patients, especially older adults (≥65 years), showed a consistently higher mortality risk than influenza patients independent of invasive ventilation or vaccination status.