What are the criticisms of the study on deaths attributed to and with COVID-19 (Coronavirus Disease 2019) during the Omicron variant surge in hospitalized patients?

From the Guidelines

The study by Basoulis et al. (2025) has significant limitations, primarily due to its small sample size, retrospective design, and subjective distinction between deaths "due to" versus "with" COVID-19, which restricts its generalizability and reliability. The study's findings should be interpreted with caution, considering the potential biases and lack of standardized criteria for classifying COVID-19 mortality. As noted in the study on the conduct of clinical trials in the era of COVID-19 1, the pandemic has introduced various competing influences on cardiovascular event rates, including fear of hospitalization, decreased patient physical activity, and potential increased adherence to therapies, which may have impacted the outcomes in the Basoulis et al. study. The limitations of the study can be summarized as follows:

• Small sample size and limited geographic scope, covering only seven hospitals in Athens, Greece
• Retrospective design, which introduces potential selection bias and relies on medical records with inconsistent documentation standards
• Subjective distinction between deaths "due to" versus "with" COVID-19, lacking standardized criteria
• Limited study period, representing only one phase of the pandemic
• Potential lack of control for confounding variables, such as vaccination status, comorbidities, and treatment protocols
• Challenges in accurately determining causality in complex cases where COVID-19 interacted with underlying conditions, as highlighted by the complexities of cardiovascular events and COVID-19 interactions 1. These limitations underscore the need for larger, more comprehensive studies with clearer methodological approaches to classifying COVID-19 mortality, as well as consideration of the broader context of the pandemic's impact on healthcare systems and patient outcomes.

From the Research

Criticisms of the Study

• The study by Basoulis et al. 2 has been criticized for its methodology in classifying deaths as "due to" or "with" COVID-19, which may not accurately reflect the true cause of death.
• The study's finding that 45.3% of deaths were unrelated to COVID-19 may be influenced by the high mean age of the patients (81.7 years) and the presence of comorbidities, which could have contributed to the deaths 2.
• The study's results are consistent with other studies that have found that the Omicron variant is associated with less severe disease and lower mortality rates compared to previous variants 3.
• However, other studies have found that immunocompromised patients are still at high risk of severe disease and death from COVID-19, even with the Omicron variant 4.
• The study's finding that co-infection with other pathogens is common in ICU patients with COVID-19 and is associated with poor outcomes is consistent with other studies 5.

Limitations of the Study

• The study's retrospective design and reliance on patient records may have introduced biases and limitations in the data collection and analysis 2.
• The study's sample size and population may not be representative of all COVID-19 patients, particularly those in other regions or with different demographics 2.
• The study's classification of deaths as "due to" or "with" COVID-19 may not be generalizable to other settings or populations 2.

Comparison with Other Studies

• The study's findings are consistent with other studies that have found that the Omicron variant is associated with less severe disease and lower mortality rates compared to previous variants 3, 6.
• However, other studies have found that immunocompromised patients are still at high risk of severe disease and death from COVID-19, even with the Omicron variant 4.
• The study's finding that co-infection with other pathogens is common in ICU patients with COVID-19 and is associated with poor outcomes is consistent with other studies 5.