This is to report on the clinical/laboratory features, the clinical course, and the outcomes of 85 patients with COVID-19, admitted in a COVID-19 designated department in a low burden European region. Our main findings are: 1) more than half (56%) of the patients had severe/critical disease, 20% required ICU care (14% received mechanical ventilation) and 10.7% died; 2) NEW2 score, solid tumors, thrombocytopenia and involvement of all lung fields in chest x-ray were independent risk factors of ICU admission; 3) Immunosuppression and thrombocytopenia were independent predictors of death.
This is the first report of Greek COVID-19 patients treated at the designed hospital wards. Greece experienced a relatively low community spread of SARS-CoV2 resulting in a moderate burden imposed on its health-care system. Until the 22th of July (date of the last follow-up assessment of our patients) only 137 patients were admitted at the ICUs and 200 died (mortality 1.865/100,000) throughout the country (data obtained by the national COVID-19 registry- https://eody.gov.gr/epidimiologika-statistika-dedomena/ektheseis-covid-19). The clinical findings of our patients on presentation are similar to those reported elsewhere [5]. Significantly, most of them had severe/critical disease and 20% required ICU support. The hospital mortality was 10.7%, mainly restricted to patients with hematological malignancy and elderly patients with several comorbidities and bacterial infections. In general, COVID-19 hospital mortality is thought to be 15-20% [5]. As expected, most data, come from severely hit countries. Liang et al. Compared to the outcomes of patients hospitalized in, or outside, Hubei (the pandemic epicenter) [6] Hubei hospitals had higher mortality, which most likely should be attributed in the substantially higher rate of comorbidities and severe disease compared to those from other regions in China. Therefore, to compare the outcomes observed in our patients with those reported elsewhere, the severity of the disease and the underlying health problems of patients should be considered. In China, Guan et al, have reported probably the lowest percentages of ICU admission (5%) and death (1.4%) in the literature [9]. However, only 15,7% of the patients had severe/critical disease and 23.7% com-morbidities – in our cohort these percentages were 56% and 72%, respectively. In contrast, Zhou et al, in patients with disease severity similar to ours but with lower prevalence of comorbidities (48%), reported 26% ICU admission and high (28.3%) mortality [10]. New York City was another region with high incidence of COVID-19 and heterogeneity in reported outcomes. Richardson et al, report 14% ICU care and 21% mortality among hospitalized patients, with median age 63 (ours 60) y.o. and 94% of them having at least one comorbidity. On admission, 20% of the patients had respiratory failure – 34% in our cohort [11]. In other words, these patients, despite being less severely ill and less often admitted in ICU, experienced double mortality compared to our patients. The higher prevalence of comorbidities may have contributed to that discrepancy. In the UK, among 20,133 patients, 17% required ICU care and 26% died [12]. The comparison of the UK cohort with ours is difficult due to the fact that the authors do not report the disease severity while, at the time of their observations’ release, 1/3 of the patients were still hospitalized. Nevertheless, mortality was significantly higher than ours, despite the similar percentage of comorbidities (76%).
In Germany, invasive ventilation was required in 17% of hospitalized patients and mortality was 22%. Mortality in the non-mechanically-ventilated population was 16% [13]. It is not clear why, although the percentage of the German patients requiring ICU was comparable to ours, significantly however, mortality was double.
How should one explain the favorable outcome observed in this study? Pharmacological treatment most likely, had no, or only a weak effect. Hydroxychloroquine plus azithromycin was given to 90% of the patients, according to the National guidelines at that time were not proved to be beneficial. Furthermore, in randomized trials [14-15]. Remdesivir, colchicine and steroids which may hinder COVID-19 [16-18] had been administered in very few patients. The use of early prophylactic anticoagulation, as standard treatment, might have positively affected survival since thrombosis is an important component of COVID-19 pathogenetic spectrum [19]. Even though clinically evident thrombotic event, except a case of acute myocardial infraction, did not occur** in our cohort, the impact of anticoagulation in COVID-19 outcomes remains highly doubtful. While pharmacotherapy for COVID-19 is still evolving, high quality supportive care remains the cornerstone of COVID-19 treatment. Therefore, the fact, that the COVID-19-designated wards were not overwhelmed and there was no lack of technical and human resources and available ICU space, made it possible for every patient with severe respiratory failure to be timely transferred from an isolated, unsupervised ward room to a proper place for monitored and advanced respiratory support. This, certainly may have an impact in overall survival. However, the fact that our patients had better outcomes than that of the German cohort, where health recourses, included ICU space and were also adequate yet inexplicable and may trigger further investigation.
In a potentially fatal disease like COVID-19, predictive and/or prognostic factors on admission are important for guiding decision-making. We found that patients with solid tumors, thrombocytopenia, increased NEWS score and involvement of all lung fields in chest X-ray at the time of their hospital admission, were more likely to need ICU care, while thrombocytopenia and immunosuppression suggested increased risk of death. In our cohort, NEWS score, known to predict in-hospital mortality [7], was found to be a predictor of ICU admission but not death. Though adverse outcomes have been linked to patient’s features such as age, male gender, and certain com-morbidities [5], findings differ between studies. For instance, in Metropolitan Detroit patients, male sex, excessive obesity and chronic kidney disease (CDK) were risk factors for ICU admission [20]. In agreement with our results, age was not an independent predictor of their patients’ ICU care and needs. However, this cohort has some distinctive characteristics: Most of its patients were female (60.3%), African American (73%), with high prevalence of CKD (36.5%) and BMI>33.6. Zhu et al found older age, d-dimers>1 ng/ml and higher SOFA score on admission to be associated with higher odds of hospital death. However, a greater proportion of patients have critical on hospital admission (26%) compared to our series (14%) [10]. Scores generated to predict COVID-19 mortality differ substantially [21-23[. Iaccarino et al, based on Italian population, identified age and Diabetes Mellitus, COPD and CKD as indicators of mortality [21]. Zhao et al did not find age to be amongst the top predictors [22], while Dong et al concluded that only hypertension and not age could predict an in-hospital death [23]. This divergence may suggest that the risk factors for ICU admission or death may critically depend on the characteristics of the population, in which these scores were developed, meaning that local validation of scores developed elsewhere may be required.
Some limitations of the present study deserve a comment. First, due to its retrospective design, data on parameters, such as BMI or ethnicity, were not available for all patients and not investigated as putative predictors of ICU admission or death. Second, the small size of the cohort and the low number of events might result in low statistical power. However, the COVID-19 ward was based in the largest hospital in the country as well as the busiest, especially, during the spring pandemic, which means that our findings probably provide a representative view of hospital COVID-19 care in low burden European regions.
In conclusion, hospitalized COVID-19 patients in a European country with a low burden of the disease, although possessing similar clinical features and disease severity, they have more favorable outcomes compared with patients from regions with a high burden of the disease. These findings might mostly be explained by the fact that the appropriate health resources were available even at the peak period of the pandemic, thus permitting the proper support of patients with severe and critical disease. This in turn highlights the vital role of prevention of the COVID-19 spread in ensuring favorable outcomes for those with more advanced disease.