key: cord-322404-lj5hfuqm
authors: Halvatsiotis, P.; Kotanidou, A.; Tzannis, K.; Jahaj, E.; Magira, E.; Theodorakopoulou, M.; Konstandopoulou, G.; Gkeka, E.; Pouritzaki, C.; Kapravelos, N.; Papoti, S.; Sileli, M.; Gogos, C.; Velissaris, D.; Markou, N.; Stefanatou, E.; Vlachogianni, G.; Aimoniotou, E.; Komnos, A.; Zafeiridis, T.; Koulouvaris, P.; Armaganidis, A.; Bamias, A.; Dimopoulos, G.
title: Demographic and Clinical Features of Critically Ill Patients with COVID-19 in Greece: The Burden of Diabetes and Obesity
date: 2020-07-17
journal: Diabetes Res Clin Pract
DOI: 10.1016/j.diabres.2020.108331
sha: 
doc_id: 322404
cord_uid: lj5hfuqm

Abstract Aims The aim of the study was to investigate the association between type-2 diabetes mellitus, other underlying diseases and obesity with the outcomes of critically ill Covid-19 patients in Greece. Methods In this retrospective observational multi-centre study, data and outcomes of 90 RNA 2109-nCoV confirmed critically ill patients from 8 hospitals throughout Greece, were analysed. All reported information stand through April 13th 2020. Results The median age of the patients was 65.5 (IQR 56-73), majority were male (80%) and obesity was present in 34.4% of patients most prevalent to younger than 55 years. Hypertension was the prevailing comorbidity (50%), followed by cardiovascular diseases (21.1%) and type-2 diabetes (18.9%). At admission, common symptoms duration had a median of 8 (IQR 5-11) days. A 13.3% of the patients were discharged, 53.4% were still in the ICUs and 28.9% deceased who were hospitalised for fewer days than the survivors [6 (IQR 3-9) vs. 9 (IQR 7-14.5) respectively]. Aging was not a risk factor but diabetes deteriorates the outcomes. Obesity poses a suggestive burden as it was more notable in deceased versus survivors. Conclusions Type 2 diabetes and obesity may have contributed to disease severity and mortality in COVID-19 critically ill patients in Greece.

The aim of the study was to investigate the association between type-2 diabetes mellitus, other underlying diseases and obesity with the outcomes of critically ill Covid-19 patients in Greece.

In this retrospective observational multi-centre study, data and outcomes of 90 RNA 2109-nCoV confirmed critically ill patients from 8 hospitals throughout Greece, were analysed. All reported information stand through April 13 th 2020.

The median age of the patients was 65.5 (IQR 56-73), majority were male (80%) and obesity was present in 34.4% of patients most prevalent to younger than 55 years.

Hypertension was the prevailing comorbidity (50%), followed by cardiovascular diseases (21.1%) and type-2 diabetes (18.9%). At admission, common symptoms duration had a median of 8 (IQR 5-11) days. A 13.3% of the patients were discharged, 53.4% were still in the ICUs and 28.9% deceased who were hospitalised for fewer days than the survivors [6 (IQR 3-9) vs. 9 (IQR 7-14.5) respectively]. Aging was not a risk factor but diabetes deteriorates the outcomes. Obesity poses a suggestive burden as it was more notable in deceased versus survivors.

In December 2019, many cases of pneumonia without a defined causative factor were reported in Wuhan China, with some patients rapidly developing respiratory distress syndrome or acute respiratory failure [1] . On Jan 7 th , a novel coronavirus was identified by the Chinese Center for Disease Control and Prevention (CCDC) from the throat swab sample of a patient and was subsequently named 2019-nCoV by WHO [2] . The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome. Most patients were men and a sizable proportion suffered from underlying conditions [3] .

The first Covid-19 case in Greece was diagnosed on February 26 th and on March 23 rd with 695 confirmed cases and 17 death, a nation-wide restriction on freedom of movement was enforced. On March 8 th , the first patient with confirmed pneumonia by 2019-nCoV was admitted in an Intensive Care Unit (ICU) due to pulmonary failure. As of April 13 th , the total Covid-19 cases in Greece were 2.145, 25.8% of patients were infected due to travel exposure and 40% of patients were infected due to close contact with diagnosed cases. The death toll was in total 99 patients, while 73 patients were supported with mechanical ventilation in critical condition and 16 patients had been discharged from the ICUs [4] .

Development of severe acute respiratory syndrome is seen more often in elderly patients with Covid-19 pneumonia and with underlying chronic diseases such as hypertension, cardiovascular diseases, type-2 diabetes, chronic obstructive pulmonary disease or malignancies [5] . There is evidence of increased incidence and severity of Covid-19 in patients with type-2 diabetes, with higher risk for ICU admission and considerable mortality [6] . In addition, obesity has been associated with disease severity and National guidelines recommend that patients with obesity and especially those with severe obesity should take extra measures to avoid Covid-19 contamination [7] . A major problem of the coronavirus pandemic is the considerable burden imposed on the National Health System worldwide due to the hyperacute outbreak and the proportional increase of patients requiring ICU support in an extremely limited period of time.

Hence, outcomes may vary according to the burden of the disease in each country. In contrast to the USA and other European Countries, Greece has been among the Countries with the lower number of cases and deaths and thus information regarding the outcomes of critically ill patients may be of interest.

The aim of this retrospective observational study, was to investigate the association between type-2 diabetes mellitus, other underlying diseases and obesity with the outcomes in Greek patients admitted to ICUs for respiratory failure caused by Covid-19 pneumonia. The relation of aging with demographics, comorbidities, clinical characteristics, need for invasive mechanical ventilation and outcomes was also evaluated.

In this retrospective observational multi-centre study, 90 patients with laboratoryconfirmed SARS-CoV-2 pneumonia (positive result on reverse-transcriptase- values (blood routine test, arterial blood gas analysis and blood chemistry with troponine levels) and chest radiography -CT findings. For the severity of the patient condition requiring intensive care the ratio of partial pressure of oxygen (PaO 2 ) to the fraction of inspired oxygen (FiO2) on admission and three (3) days later was used.

Additionally we collected data regarding the proportion of patients that required mechanical ventilation, the length of stay in ICU, the number of patients who died while under observation and treatment, those who were discharged from the Units and those who were still in ICUs. No imputation was made for any missing data. Diabetes was defined from the patients' medical history and type-1 patients were excluded from the study. Decisions regarding admission, management and intubation per patient, were made by the individual referring physician. The defined outcomes of the study, were the burden of diabetes and obesity in critically ill Covid-19 patients. All reported information stand for hospitalization through April 13 th 2020.

Sample size was equal to the number of patients treated during the study period in the collaborating hospitals. Descriptive statistical analysis was performed for all study data.

Continuous variables were summarized through the use of medians (25 th -75 th percentiles) and categorical variables were displayed as frequency tables (N, %). 

The analysis included 90 critically ill patients with a median age of 65.5 (IQR 56-73).

Since age has been shown to be associated with outcomes [14] [15] 

Twenty-seven patients (30%) had no any underlying disease. Arterial hypertension was the most prevalent comorbidity affecting 45 patients (50%), followed by 19 patients with cardiovascular diseases (21.1%), 17 with type-2 diabetes (18.9%), 8 with COPD (8.9%), 7 with malignancies (7.8%), 4 with chronic kidney disease (4.4%) and 3 with asthma (3.3%). Thirty-seven patients presented with only one comorbidity (41.1%), 15 with two (16.7%), 9 with three (10%), 1 with four (1.1%) and 1 with 5 (1.1%). More patients in Group C had at least one comorbidity (86.7%) compared to Group B (66.67%) and Group A (38.1%) (p=0.001). The same Group was also associated with higher frequency of more than 2 underlying diseases ( Differences within the study groups were statistically significant (p=0.024). Obesity was more frequent (46.2%) among deceased than among survivors (26.7%) (p=0.077).

The median age of the living patients without obesity is 67 (IQR 62-74.5) and it is statistically significantly higher than those with obesity 55.5 (IQR 51.5-65.5) (p=0.007). The deceased patients median age is 66.5 (IQR 52-73) in non-obese & 64.5 (IQR 54.5-67) in obese (p=0.505). {Figure 2}.

Only 8 patients (8.9%) were admitted directly to ICUs, while the median duration of the common symptoms before their appearance in the Emergency Rooms was 8 (IQR 5-11) days, with similar distribution in all age study groups (p=0.381). However, the reported symptoms lasted fewer days in the deceased patients (6.5 [IQR4-10]) than in the survivors (8 [IQR 5-12]) (p=0.043). Vital signs at admission in ICUs, was fever ≥ 38 0 C for 64 patients (71.1%), heart rate ≥ 100 beats/sec for 49 (54.5%) and respiratory rate with ≥ 20 breaths per minute in 87 patients (96.7%).

The laboratory and radiologic findings of the patients upon admission in ICU are shown in Table 2 . Laboratory data for 19 patients from one collaborating center was not submitted. However besides a suggestive trend of higher arterial lactate levels in nonsurvivors there was not found any other differences for the baseline values of all laboratory parameters measured {Table 3}.

Abnormal findings with bilateral pulmonary opacities were detected in all but one patient and pleural effusions were seen in 24 (26.7%). Pleural effusion was more frequently found evident in Groups B (n=11, 61.1%) and C (n=11, 28.2%) in comparison to Group A (n=2, 14.3%) (p<0.013). 

Twelve (12) Therefore, in our study, there is no evidence that age is a factor which adversely complicates the health outcomes of a patient in a critical care status from Covid-19.

The median days of hospitalization was 8 (IQR 5-13), which was similar in all three study groups, namely 7 (IQR 5-12) in Group A, in Group B and 9 (IQR 6-13) in Group C. However, deceased population was hospitalised for a shorter period than survivors 6 (IQR 3-9) days vs. 9 (IQR 7-14.5) (p=0.002) {Figure S1}.

In this observational retrospective study, the collaborating hospitals, cited from North to South Greece in different major urban locations, provided information for the disease course of patients hospitalized in their ICUs and thus is representative of cases diagnosed and treated Nationwide. The median age [65.5 (IQR 56-73) years] and the gender propensity of our patients (mostly men) are similar to critically ill Covid-19 patients in neighboring countries or in the USA [5, 14] . Our findings identified that the duration of reported known symptoms [15] with a median duration of 8 days prior to admission and hospitalization was shorter in non-survivors vs survivors (p=0.043, p=0.002 respectively).

The vast majority of our patients needed mechanical ventilation upon ICU admission because of severe to moderate acute respiratory distress syndrome as indicated from the very low ratio of PaO 2 /FIO 2 [16] . In contrast to reports from Italy [5] , statistically significant improvement of the ratio was seen only to older than 66 years old patients and although half of all patients were older, the mortality between age study groups was similar. Most studies demonstrate that mortality is significantly lower in younger ages (<65 years), probably because cardiovascular and metabolic disorders are very common in older patients and may influence the true impact of aging to prognosis [17] . Our patients over 65 years had statistically significant higher number of comorbidities than the younger ones (p=0.001) without however any increased rate of mortality though.

The patients in this study meet the rates of comorbidities for the general population in Greece [18] .

Obesity is associated with a negative role in respiratory function [19] [20] and the elderly patients in our study had a lesser degree of obesity. Literature suggests that obese patients are presented with more severe Covid-19 infection [21] [22] . Obesity in our patients was relatively high, particularly in the younger group (p=0.009) and with a suggestive relation to increased mortality (p=0.077). Furthermore, the age of the survivors without obesity was higher than the obese survivors (p=0.007).

Undoubtedly, diabetes mellitus is now recognized as one of the most common commorbidities in Covid-19 patients [14] and since many diabetic patients are obese this leads to a twofold increase in the incidence of requiring intensive care [23] . In our study a suggestive association of diabetes (p=0.056) with mortality has been noted, as it was present more frequently in non-survivors (30.8%) vs survivors (13.3%). It is also noteworthy that none of the 12 discharged patients had diabetes, while it was present in 30.8% of the deceased. Even more the number of the non survivors with diabetes was significantly higher regardless the age study groups they belong (p=0.038) {Figure S2}. Thus, people with diabetes appear to develop with an increased risk a more severe Covid-19 infection, but the mechanisms and the underlying molecular pathophysiology remains still uncertain.

A systematic review from China demonstrated that patients suffering from previous CVD may face a greater risk of developing severe condition [24] . Conversely, our results indicate that the presence of CVD was not related to early death, since the frequency of CVD was similar between non-survivors (15.4%) and survivors (23.3%), but was clearly and significantly present to our population of the elder patients (p=0.001).

Nevertheless, our study has some limitations. We evaluated data extracted retrospectively from patients' medical files, not all laboratory tests were done in all patients and the patient study size was small. The survivors group might not reflect the true case fatality rate, because we are not aware of the progress of the disease for every single patient who remained hospitalized at the time when data were locked. Even more we did not proceed to a complete multivariate sub-group analysis with all confounding factors mainly because the small sample size and thus the significance of our results would be then very weak with a wide spread in confidence intervals. Certainly, a more thorough assessment of comorbitidies, may help establish a risk stratification of patients with Covid-19 upon hospital admission and thus future studies are needed. 

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The authors thank the staff who carried out the extensive clinical and nursing work in the Intensive Care Units where the study patients were hospitalized. 

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

All authors declare no conflict of interests