The SEARCH-COVID-19 study analysed the characteristics and outcomes of 2139 ICU patients during the 1st and 2nd waves of the COVID-19 pandemic. To the best of our knowledge, this is the largest dataset from Central-Eastern European countries on this patient population to date. This multicentre, international study with a comprehensive dataset on COVID-19 patients treated on the ICUs in six Central-Eastern European countries revealed that both overall mortality and especially those receiving invasive mechanical ventilation had substantially higher mortality compared to that reported in previous studies from Western European countries.
The 2 years of the COVID-19 pandemic represent an unprecedented period in medicine, challenging health care systems all around the globe and provoking research activity the like of which the medical community has never seen before. Intensive care medicine has played a crucial part in the fight against the devastating effects of the virus. Despite all efforts, more than 5.6 million people have died around world to date due to the corona virus affecting every single country on the planet . The number of patients infected, admissions to hospital and ICU, and mortality have varied over time and by country to country. In a recent article Islam and colleagues showed that COVID-19 resulted in a huge number of excess deaths exceeding the reported actual COVID-19 deaths and suggested that assessment of the full impact of the pandemic on mortality should include both the direct effect of the pandemic and the indirect influence on deaths from other causes associated with the disruption to health services or wider economic and social changes . Even though national governments have reported the number of deaths from COVID-19 daily, scientific publications from Central-Eastern Europe remain scarce. This has also been shown by a recent meta-analysis in which all papers reporting case fatality rates were analysed, and although Europe contributed thousands of patients from several countries, no suitable study was found during the systematic search that included countries from Central-Eastern Europe .
Patient characteristics and management
Regarding age, patients in our cohort admitted to ICU belonged primarily to the elderly population (>65 years of age) with higher prevalence of males than females. These and also the patients’ body mass index were similar to that of reported by other studies [3, 5, 12]. Only 12% of patients were free of any comorbidities, which is substantially lower than reported by one Italian cohort (32%) , but similar to that of found in another study (22%) . Patients were admitted to ICU 5 - 6 days after the onset of symptoms and stayed on the ward 1 - 2 days in general. This is again similar to that observed in other studies [13, 14], but 2 days shorter than reported in non-survivors in a French single centre study .
The general condition of the patients on admission as indicated by APACHE II scores were similar to that of reported in the Intensive Care National Audit & Research Centre (ICNARC) database . Admission median SOFA score of the non-survivors in our study was 8, which is substantially higher than that reported in a recent single centre study of 73 deceased patients (median: 4, IQR: 3-8) . These data suggest that our population was slightly sicker but there are no obvious differences that have been shown to be associated with worse outcomes in COVID-19 patients.
We also analysed the cause of death, which was in accord with that reported in other studies, with refractory respiratory failure and sepsis accounting for 75% of all deaths. This was found to be the same in a single centre French study .
The median duration of stay in the ICU in our study was 9 days (10.5 for survivors, 9 for non-survivors) which was longer than in the ICNARC dataset (5 days for both survivors and non-survivors), but similar to that of reported by others [10, 15]. Regarding treatment modalities our data suggest that patients in general were treated more-or-less according to international recommendations.
These data suggest that based on the overall characteristics our patient population was not that different to those included elsewhere in Europe. Furthermore, it is highly likely that patients received similar treatment modalities including ventilatory support, medication and ECMO.
The most important results of our study are the higher overall mortality especially those needing mechanical ventilation in our region compared to most of the reports coming from the Western European countries. Needless to say, external validity of our results is compromised due to the relatively small sample size and limited number of participating ICUs. Therefore, we cannot conclude that our results are generalizable for the whole region. However, as there are no other large sample size studies published on this topic to contradict our results and taking into account the epidemiological data published on international official websites , we consider the message of our data as an alarming signal that should be taken seriously and investigated thoroughly in the future.
The odds ratio for mortality showed substantial differences in the participating centres, but this heterogeneity is a common feature all around the world as indicated for example by the meta-analysis by Lim et al. . Despite the low number of patients, ICU mortality during the 1st wave was around 40%, which increased during the 2nd wave to 56%. As compared to international data, in one of the very first reports on 1590 patients from Grasselli et al., 88% of patients were mechanically ventilated and overall mortality was 25% . The “COVID-19 Italian ICU Network” reported that out of 1260 patients treated during the 1st wave, 79% underwent invasive mechanical ventilation and that mortality among intubated patients was 38.5% . In the United Kingdom, according to the ICNARC reports, during the 1st wave, overall mortality was 50.7% which reduced to 35.2% in the report released a year later on the 26 February 2021 .
Data from other countries are less positive. In Germany despite the drop in ICU admissions during the second wave of the pandemic, the mortality of mechanically ventilated patients remained unchanged and also above 50% . According to the COVID-19 SEMICYUC Working Group (from Andora, Ireland and Spain) mortality was lower, but without significant differences between the waves (31.7% versus 28.8%) .
Although a multicentre international study in 2625 patients also reported reduced survival rate in the 2nd wave (30 days: 1st wave 43% vs 2nd wave 50%, and 90 days: 1st wave 49% vs 2nd wave 60%), this study only included the elderly population aged 70 years and older . In this study out of the 14 countries, there was only 1 included from Central-Eastern Europe (Poland), who contributed 102 patients from 12 centres, hence comparisons between their results and ours are difficult to make. Nevertheless, this data also supports the finding in our study, that the 1st wave in Central-Eastern Europe was less severe as compared to the West as, from the 12 Polish centres, only 12 patients were included during the 1st and 90 in the 2nd wave.
In our dataset, 66% patients were mechanically ventilated which is substantially less than the 88% in the previously mentioned Italian study, but the mortality showed a dramatic difference of 66% in our study versus 25% in theirs . The same conclusion can be drawn when we compare our results to that of reported by ICNARC on 6501 invasively ventilated patients where mortality was 46.8% during the 2nd wave . Furthermore, overall mortality in a meta-analysis on invasively ventilated patients all around the world was 45% (95% confidence interval 39-52%), which is again lower than in our cohort .
Regarding in hospital mortality of patients receiving only non-invasive respiratory support, it was 39% for HFNO, 50% for non-invasive ventialtion and 22% for conventional oxygen therapy. These results are worse when compared to the most recent results of the RECOVERY-RS trial, which revealed that 30-day total mortality occurred in 21.2% and 22.3% in patients on HFNO and conventional oxygen therapy, respectively .
Unfortunately, we have limited published data from Central-Eastern European ICUs [19-22] to compare our data to, but the current results on mortality match with those published on the national and international websites, suggesting that mortality of COVID-19 patients in the six countries included in the current analysis was somewhat higher than in our Western European counterparts .
Undoubtedly, we cannot present data that could explain this potential difference in mortality between the two parts of Europe (i.e.: Central-East vs West). One cannot exclude that the indication and potential delay in commencing the invasive ventilator support may be one of the critical points as to why patients in the 2nd wave of our study did worse than others. Our patients’ overall median APACHE II score was 17. Mortality of patients admitted with a similar APACHE II score (17+) in the ICNARC database also had similar 28-day mortality to that of ours of around 57% as reported on 26.02.2021 . Furthermore, the median PaO2/FiO2 on admission was 99 mmHg in our study, that is lower than reported in some other studies with better outcomes [3,4]. These may suggest that our patients, despite the crude similarity in demographics and patient characteristics were still sicker.
Furthermore, there are some well-known circumstances that may have played an important contribution if this difference truly exists. On the one hand, the “one way traffic” of health care personnel from countries of the former socialist block of Europe (i.e.: Central-Eastern Europe) including the six countries participating in the current study has been going on for decades. Although this exodus of the Central-Eastern European work force to the West is well known and acknowledged, it has never been audited, researched, and most importantly never been published in scientific journals. Therefore, the subjective assessment of the authors of the situation, that the most important factor of unfavourable outcome in COVID-19 critically ill patients might be related to lack of personnel, should be taken seriously. Although a recent publication coming from Australia-New Zealand found no association between patient-to-intensivist ratio and hospital mortality , these results may not be applicable for the eastern part of Europe for reasons pointed out earlier and will also be discussed later. Even in the editorial for the same article the authors clearly emphasize the potential importance of the strain on the critical care workforce  that is also supported by recent publications [25, 26]. Adding these issues to the lack of trained personnel could indeed have a major impact on outcomes.
On the other hand, it has also been well documented that the Gross Domestic Product (GDP) related spending on health care is substantially less in Central-Eastern Europe then in Western Europe (Supplementary Table 3, S6, S7). This could also have a profound effect on the observed exodus from East to the West, which may be an important potential factor of worse outcomes than that reported from Western European countries.
Last but not least, structured training and overall motivation of junior doctors and other health care workers, especially specialised nurses, should also be reviewed and improved .
Finally, to confirm or contradict the validity of our results, nationwide and internationally, well structured, transparent, trustworthy audits, registries and studies are needed, ideally supported by governmental funding. The goal should be to develop a system and structure, which is similar to that of those developed in Western Europe and in the United Kingdom [3, 5].
Strengths and limitations
Although this is the most comprehensive and largest dataset ever published from Central-Eastern Europe on COVID-19 patients treated on the ICU, it has several limitations. The most important is that our dataset cannot be considered as representative data for the whole region, not even for these six countries, which limits its external validity. Nevertheless, it is important to note that Central-Eastern European clinical research was unable to compete in the publication “race” neither before, nor during the pandemic. The contribution of this part of Europe to the unprecedented number of scientific papers published from all over the world remains negligible. In our view this is a system failure that is also supported by the fact that we could not include a single patient in the SEARCH study prospectively, simply because of the inadequate staffing levels on the ICU who were overwhelmed, and the almost complete lack of research dedicated personnel. This leads to the other important limitation, which is the retrospective nature of the study, resulting in reduced number of data on COVID-19 related admissions and outcomes during this period, organ support related parameters which we could not collect retrospectively, nor the patient-to-nurse/physician ratio, or specialised nurse-to-patient ratio.