Influenza A Virus Exposure May Worsen COVID-19 Symptoms and Increase Deaths

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Influenza A Virus Exposure May Worsen COVID-19 Symptoms and Increase Deaths

During the early months of the COVID-19 pandemic, a hidden risk overlapped with the crisis: influenza A virus (IAV), the main cause of seasonal flu. Both viruses trigger fever, cough, and fatigue, and IAV circulates heavily from December to February in the Northern Hemisphere—exactly when COVID-19 first spread globally. But how does recent IAV exposure affect people with COVID-19? A 2020 study from China offers critical insights into this understudied question.

The Study: Who, What, and How

Researchers from Peking University First Hospital (Beijing) and Tongji Hospital (Wuhan)—a frontline institution during the initial COVID-19 outbreak—analyzed data from 70 COVID-19 patients admitted between January 28 and February 25, 2020. All patients had confirmed COVID-19 via PCR tests and chest CT scans. To focus solely on IAV’s impact, the team excluded anyone with signs of other respiratory infections.

To check for recent IAV exposure, doctors tested patients’ blood for anti-IAV immunoglobulin M (IgM)—an antibody that appears 1–2 weeks after infection and remains in the body for 2–3 months. This helped divide patients into two groups:

  • IAV-positive: 32 patients (45.7%) with recent IAV exposure.
  • IAV-negative: 38 patients with no signs of recent IAV exposure.

The team then compared symptoms, inflammation markers (like cytokines that signal immune activity), disease severity (common, severe, critical), and death rates between the groups. They also looked at whether taking oseltamivir—a prescription flu drug—changed outcomes.

Key Findings: IAV Exposure Linked to Worse Outcomes

The results revealed three critical trends:

  1. More Systemic Symptoms: IAV-positive patients were 1.7 times more likely to report fatigue (59% vs. 34% in IAV-negative patients)—a sign of more severe systemic illness. Women were also overrepresented in the IAV-positive group (59% vs. 34%), which researchers note may reflect higher susceptibility to certain IAV subtypes.

  2. Inflammation Marker Surprises: While both IAV and COVID-19 typically raise inflammation markers like soluble interleukin 2 receptor (sIL-2R) and tumor necrosis factor alpha (TNFα), these levels were lower in IAV-positive patients. The team suspects this reflects complex immune interactions between the two viruses—something future studies need to explore.

  3. Dangerous Outcomes Trend: IAV-positive patients were twice as likely to be critically ill (31% vs. 16%) and nearly three times more likely to die (22% vs. 8%) than IAV-negative patients. While these differences weren’t statistically significant (likely due to the small sample size), they suggest IAV exposure could worsen COVID-19.

  4. Oseltamivir Saved Lives: For IAV-positive patients, taking oseltamivir before admission was a game-changer. None of the 13 patients who took oseltamivir died—compared to 37% (7 of 19) who didn’t. Oseltamivir had no effect on IAV-negative patients, proving the benefit was specific to IAV exposure.

Why This Matters for Flu Season and COVID-19

The study’s biggest takeaway is simple: during flu season, doctors must check for IAV exposure in COVID-19 patients. IAV and COVID-19 share symptoms, so it’s hard to tell them apart without testing—but the consequences of missing IAV could be deadly.

The oseltamivir finding is especially important. In the early pandemic, doctors often prescribed oseltamivir empirically (without confirmed flu) because flu and COVID-19 symptoms overlap. This study suggests that for patients with recent IAV exposure, that decision could save lives.

Limitations and Next Steps

Like all research, this study has gaps:

  • Retrospective Design: The team looked back at past data, which can introduce bias (e.g., more severe patients may have been tested for IAV).
  • Small Sample: Only 70 patients were included—too few to confirm strong statistical links between IAV and COVID-19 deaths.
  • No IAV PCR Testing: IgM shows recent exposure but can’t confirm active IAV infection (co-infection) vs. past infection (consecutive illness). PCR tests on nose/throat swabs would have clarified this.
  • Symptom Recall: Most patients didn’t report prior flu symptoms, but self-reporting can be unreliable.

To build on these findings, researchers need prospective studies (following patients forward in time) with larger samples. They also need to use PCR tests to confirm active IAV infection and test lower respiratory samples (like sputum) to see if IAV causes pneumonia in COVID-19 patients.

The Bottom Line

For patients and doctors, the message is clear: flu season and COVID-19 are a dangerous combination. If you have COVID-19 symptoms during flu season, ask your doctor about IAV testing. And if you’re diagnosed with both, oseltamivir may help—especially if given early.

This study is a small piece of the puzzle, but it highlights a critical truth: in pandemics, we can’t fight one virus at a time. We need to watch for overlapping threats—and act fast when we find them.

This study was published in the Chinese Medical Journal in 2020 by Zhan-Wei Hu, Xi Wang, Jian-Ping Zhao, Jing Ma, Hai-Chao Li, Guang-Fa Wang, Yuan Cheng, and Hong Zhang. Read the full paper here: doi.org/10.1097/CM9.0000000000000966

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