Analysis: COVID-19, Flu Coinfection Not Linked to Worse Outcomes, Mortality

Despite heightened public worry over "florona" cases, a meta analysis from China suggests co-infection of the respiratory viruses is not associated with more severe outcomes.

Despite heightened concern over SARS-CoV-2 and influenza coinfection—dubbed “florona” in public discourse—a recent systemic review and meta-analysis of such cases showed no differing risk of mortality in COVID-19 patients who also tested positive for the flu.

Interestingly, the assessment from a team of China investigators showed that COVID-19 and flu coinfection patients actually experienced a lower risk for severe outcomes with either disease than standard patients with COVID-19.

Led by Zhou Guan, of the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases at the National Clinical Research Centre for Infectious Diseases, investigators soufght to estimate the impact of SARS-CoV-2 and flu coinfection on patients compared with single SARS-CoV-2 infection. As they noted, coinfection has been “widely detected” and observed in case studies since the beginning of the pandemic—but most published work focuses on severe disease in high-risk patients.

“Observational studies with systematic analysis of clinical outcomes in coinfected patients compared with those mono-infected are limited,” Guan and colleagues wrote. “Considering the magnitude of the ongoing COVID-19 pandemic and the need for effective therapeutics, timely meta-analyses can play an important role in assessing the effects of influenza coinfection among COVID-19 patients on clinical outcomes such as mortality.”

Investigators assessed 4 databases for relevant research on SARS-CoV-2 and influenza coinfection occurring up to July 9, 2021. They pooled risk effects via fixed or random effects models.

Their final assessment included 12 studies with 9498 patients analyzed for the severity of coinfection, to compare against a control of patients with single SARS-CoV-2 infection.

Coinfection was not significantly associated with increased mortality (OR, 0.85; 95% CI, 0.51 – 1.43; P = .55), but investigators did observe significant differences in coinfection mortality observed in China studies (OR, 0.51; 95% CI, 0.39 – 0.68) and otherwise international studies (OR, 1.56; 95% CI, 1.12 – 2.19).

Critical outcomes were at a notably lower risk for coinfection patients versus control (OR, 0.64; 95% CI, 0.43 – 0.97; P = .004) from the 5 studies observed in China (4) and England (1).

“In respect of other disease outcomes, two studies used an outcome definition as aggravated or death, and two studies reported data on hospital stay of patients,” investigators noted. “However, no significant association was detected between coinfection and these outcomes.”

No significant association was observed between coinfected patients and risk of fever (OR, 1.02; 95% CI, 0.71 – 1.45; P = 0.93), cough (OR, 0.86; 95% CI, 0.64 – 1.15; P = .31), nor dyspnea (OR, 0.75; 95% CI, 0.55 – 1.02; P = .07) versus patients with lone SARS-CoV-2 infection across 5 relevant studies.

The team concluded that, though both viruses can separately result in severe disease, hospitalization and death—particularly among high-risk populations—coinfection had no perceptible effect on patient mortality nor severe disease risk. That said, the differing outcomes observed in China and otherwise international studies warrant more “well-designed controlled studies” as well as assessment into the mechanism of coinfection.

“Considering that co-circulation of these two viruses could have a considerable impact on morbidity and mortality, systematic testing for influenza coinfection in COVID-19 patients is necessary, and influenza vaccination should be recommended not only to reduce the risk of coinfection, but also for the potential benefits to immune system,” they concluded.

The study, “Impact of Coinfection With SARS-CoV-2 and Influenza on Disease Severity: A Systematic Review and Meta-Analysis,” was published online in Frontiers in Public Health.