Our analysis confirms the earlier findings of our previously published study, indicating that in-hospital mortality of severely ill COVID-19 patients is adversely affected by high patient load [3]; indeed the associations between patient load and mortality were nearly identical to our previous analysis, but now with significantly higher precision (narrower 95% Confidence Intervals). This shows that patient outcomes are affected not just when healthcare capacity is stressed to depletion, but also at lower levels despite the availability of care not nominally being restricted. This represents a major preventable factor to limit avoidable deaths from COVID-19, and points towards more extensive investment towards preparedness and resilience in healthcare. We also re-confirmed substantial regional disparities, with in-hospital mortality being lower in Thessaloniki and even lower in Attica compared to the rest of the country, highlighting the chronically uneven regional distribution of healthcare resources in Greece [6].

A major new finding is the 21% higher mortality observed in the period starting September 2021, which increases even further for patients hospitalized in the rest of the country (an additional +64%, compared to +36% for the previous period). This suggests that conditions in healthcare services over the past year may have further deteriorated, especially in rural areas (outside Attica and Thessaloniki). It must be noted that from September 2021 the government suspended those healthcare workers that remained unvaccinated against COVID-19 (although many of them eventually got vaccinated and returned to duty, or were replaced with newly hired personnel). Our data cannot prove a causal association between this disciplinary action and the increased mortality, but the temporal coincidence is still worrisome and merits further exploration into the precise causes of this worsening healthcare system performance.

Our analysis reconfirms that being intubated outside an ICU is associated with twice higher mortality than patients inside an ICU, although again this must be interpreted with caution; patient selection (prioritizing for ICU admission those with a higher chance of survival) may account for a large part of this association. On the other hand, we found no statistically association between mortality and the number of COVID-19 vaccine doses received; this suggests that despite vaccination being enormously effective in preventing COVID-19 severe disease and death [7], if a patient has already been intubated as a result of COVID-19 severe disease, it is quality of care and not vaccination that can prevent further deterioration and death.

In fact, the observed non-significant trend towards higher mortality among those having received two or three vaccine doses may be the result of some uncontrolled confounding due to comorbidities, as older people and those with comorbidities tend to be more frequently vaccinated. Indeed, the lack of information on comorbidities and baseline health status is the most significant limitation of our analysis; nevertheless, these factors are unlikely to be differentially distributed over time and with different patient loads, and are both eclipsed by age, which is the major determinant of the risk of death and which we carefully adjusted for [8, 9]. Therefore residual confounding by baseline health is unlikely to have affected these results to any substantial extent.

As a result, the observed associations are most likely to reflect real and avoidable differences in the quality of care for COVID-19 patients due to increased patient load, regional disparities and ICU availability, as well as a true deterioration after 1 September 2021. The findings highlight the need for urgent strengthening of healthcare services in Greece, in order to improve their performance and ensure equitable access to high-quality care for all [10].