Comparative Analysis of COVID-19 and Seasonal Influenza: A Detailed Study on Long-term Health Outcomes and Healthcare Utilization


COVID-19 and seasonal influenza, two respiratory illnesses, present significant health risks, particularly after hospitalization. While previous research has extensively analyzed short-term outcomes within 6 months post-infection, this study delves into the long-term impacts, comparing the risks and healthcare burdens beyond 6 months for both diseases.

Background and Research Methodology

A comprehensive review of literature from December 12, 2019, to September 10, 2023, was conducted, focusing on patients hospitalized for COVID-19 and influenza. This study, leveraging the expansive health-care databases of the US Department of Veterans Affairs, involved a cohort of 573,612 individuals tested positive for SARS-CoV-2 and 50,509 for seasonal influenza. The analysis included a detailed examination of 94 health outcomes over 18 months, categorizing them into ten major organ systems.


The study revealed that both COVID-19 and seasonal influenza result in significant health challenges post-hospitalization. However, COVID-19 patients showed higher risks across most organ systems, except for the pulmonary system where influenza had a greater impact. This suggests a distinct systemic manifestation of SARS-CoV-2 compared to the more pulmonary-focused nature of influenza.

Long-term Impacts and Healthcare Utilization

A key finding was the higher burden of health loss in the post-acute phase for both illnesses, underscoring the need to consider these infections beyond their immediate acute effects. The cumulative burden was notably higher in COVID-19 patients, indicating a more profound long-term impact on health. Additionally, the study highlighted a significant use of healthcare resources post-hospitalization, with COVID-19 leading to more frequent readmissions and intensive care needs.

Subgroup Analysis

The study also segmented COVID-19 patients based on the dominant virus strains (pre-delta, delta, omicron) and analyzed outcomes against influenza patients. Variations in health outcomes were observed across these subgroups, further elucidating the evolving nature of the COVID-19 pandemic.

Vaccination Impact

An important aspect of this study was examining the effect of vaccination status on health outcomes. Comparisons were drawn between unvaccinated and vaccinated individuals for both COVID-19 and influenza, offering insights into the protective benefits of vaccination.

Statistical Approach and Sensitivity Analysis

The research employed a rigorous statistical methodology, including power analyses, propensity score weighting, and multiple sensitivity analyses. These approaches ensured a robust and comprehensive assessment of the risks and burdens associated with each disease.


In this comparative analysis, we have explored the long-term health outcomes of individuals admitted to the hospital for COVID-19 versus those admitted for seasonal influenza. Our objective was to understand the differences in death rates, adverse health outcomes, and healthcare utilization between these two viral infections. Additionally, we aimed to assess the burden on various organ systems and to evaluate the role of acute and post-acute phases in contributing to overall health loss.

High Burden of Death and Health Loss

The study reveals a stark reality: both COVID-19 and seasonal influenza result in substantial rates of death, adverse health outcomes, and healthcare utilization. However, the impact of COVID-19 is significantly higher than that of seasonal influenza. This holds true even when considering the larger number of hospital admissions for COVID-19 compared to seasonal influenza, highlighting the urgent need for public health strategies to prevent infection and reinfection, vaccination, and the use of antivirals, particularly among vulnerable populations.

Respiratory vs. Multisystemic Nature of the Viruses

The comparative evaluation of organ system involvement suggests that seasonal influenza is primarily a respiratory virus, with a higher burden on pulmonary organ systems. In contrast, COVID-19 exhibits a multisystemic nature, impacting various organ systems beyond the respiratory system. Understanding the mechanistic underpinnings of these differences could pave the way for potential therapeutic interventions to improve clinical outcomes. Moreover, the multisystemic nature of COVID-19 offers opportunities for integrated care across different phases of illness.

Acute and Post-Acute Burden

Both COVID-19 and seasonal influenza impose a heavier burden of health loss during the post-acute phase compared to the acute phase. This emphasizes that focusing solely on the acute phase underestimates the overall impact of these infections. Moreover, COVID-19 shows a higher burden of health loss in both acute and post-acute phases compared to seasonal influenza, indicating a longer-term risk horizon for organ damage. This underscores the importance of providing post-acute care following hospital admissions for both viruses, with a potentially greater need for COVID-19 patients. Effective post-acute care can not only manage sequelae but also improve health outcomes while reducing the necessity for costly healthcare utilization, including repeat hospital admissions and intensive care.

Strengths and Limitations

This study boasts several strengths, including a large dataset from the VA, a comprehensive analysis of various health outcomes, and robust sensitivity analyses that consistently support our findings. However, limitations must be acknowledged. The study population is primarily older white males, limiting generalizability. We focused on hospitalized cases, so our findings may not apply to milder infections. Temporal changes in care and awareness could affect results. Although we adjusted for various factors, biases may still exist. The study considered a comprehensive set of health outcomes but might have missed yet-to-be-associated outcomes. Furthermore, our study design cannot assess differences in COVID-19 outcomes by era or between specific influenza subtypes.


In summary, our analysis underscores the immense burden of death, health loss, and healthcare utilization associated with hospital admissions for COVID-19. While seasonal influenza also leads to significant health consequences, the impact of COVID-19 is substantially higher. This emphasizes the critical need for strategies to prevent both infections and the importance of post-acute care to mitigate the burden of health loss in populations. As we continue to grapple with the evolving landscape of viral infections, understanding the unique characteristics and risks associated with each virus will remain crucial in guiding public health policies and clinical interventions.

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