4 DISCUSSION
Our study reports the analysis of clinical characteristics and outcomes
of 20 confirmed COVID-19 patients characterized by severe disease. Nine
(45%) of these patients died within 35 days of admission to the
hospital.
Our critically ill patients with COVID-19 were older which is in line
with other studies.8,18 In previous studies involving
severe COVID-19 patients, most common symptoms were fever, cough,
fatigue, and dyspnea.6-8,9,11,18 Similarly, the
incidence of cough, fatigue or myalgia, fever, and dyspnea on admission
in our study were 95% (n=19), 90% (n=18), 85% (n=17) and 80% (n=16)
respectively. In these patients mean duration of symptoms was 11±9 days
from onset to ICU admission, and the previous studies reported similar
(from 7-12 days) duration of symptoms prior to ICU
admission.5,7,9,11
More than half of the patients (n=11, 55%) in our center had underlying
diseases, similar to the data reported by the study from Wuhan (n=64,
46%).8 However, a much higher percentage of patients
has been reported in other studies.7,18 Similar to the
previous studies,8,18 hypertension was the most common
comorbidity, followed by cardiovascular disease and diabetes in our
study. This requires more follow-up data for the observation of
hypertension, the hypertension treatment received by the patient, and
the assessment of high-risk factors.
With regards to laboratory indicators, 11 (55%) patients in our center
developed lymphocytopenia on admission, and it mainly occurred in the
death group (n=8). Decreased lymphocyte count was significantly
associated with the death of COVID-19 patients in ICU. This
is consistent with the results of a single factor analysis of the
retrospective study from Wuhan.8 Previous studies of
Severe Acute Respiratory Syndrome [SARS] and Middle East Respiratory
Syndrome [MERS] have also found lymphopenia in their
studies. Studies have confirmed that lymphopenia is one of the earliest
changes in SARS and a reliable prognostic indicator of
SARS.19 In addition, studies have also shown that MERS
coronavirus can induce T cell apoptosis through the activation of
apoptotic pathways.20 In several previous studies on
moderate disease patients infected with SARS-CoV-2, only
35%6 and 40%5 of patients had mild
lymphopenia, whereas in other studies severe SARS-CoV-2 associated
lymphopenia occurred in more than 70%12 and
80%11 of the infected patients, suggesting that
lymphopenia may reflect the severity of SARS-CoV-2 infection.
Most critically ill patients in our center had an increased LDH (n=17,
85%) when they were admitted, slightly higher than the
76%6 and 67%5 observed in patients
from the other studies. All patients in our study had elevated D-dimers
on admission, and 15 (75%) patients had D-dimers > 1
mg/L. However, in the study of moderate disease COVID-19 patients, only
36% had an increase in D-dimer.6 Another early study
from Wuhan also showed that ICU patients had a higher level of D-dimer
(median D-dimer level of 2.4 mg/L) than non-ICU patients (median D-dimer
level of 0.5 mg/L). Studies have also found that D-dimer >
1 mg/L has been associated with increased mortality of
patients.5 Our study did not observe differences
between survival and death groups in terms of D-dimer, which may be
related to small sample size. The CRP of all patients in our study was
increased to 101.46±65.60 mg/L, which was much higher than the average
CRP in moderate disease COVID-19 patients, 51.4±41.8
mg/L.6 The probability of CRP increase (100%) was
also higher in our study than that of moderate disease COVID-19
patients, 60.7%18 and
86%.6 Similarly, the probability of elevated ProCT
(85%, n=17) was much higher in our study than the 6% to 30%
probability found in moderate disease COVID-19 patient
studies.6,5,18 It is, therefore, suggested that
secondary bacterial infection may be a complication in severe patients
and cannot be disregarded.
Mechanical ventilation is the main supportive treatment for COVID-19
critically ill patients. In our study, only six patients (30%) received
further IMV treatment, which is much lower than reported in other ICU
patients: 88% (Lombardy, Italy),10 47%
(Wuhan),8 42% (Wuhan),11 and 30%
(Wuhan).7 Non-invasive ventilation was used more
frequently, with 70% of patients receiving NIV in our study, as
compared to the rate of NIV use in other ICU studies: 42%
(Wuhan),8 56% (Wuhan),11 and 62%
(Wuhan).7
Acute hypoxemic respiratory failure caused by ARDS has been found to be
the most common complication (60% to 70% of patients admitted to the
ICU), followed by shock (30%), myocardial dysfunction (20% to 30%)
and acute kidney disease injury (10%~30%) [5,6
9-11].7-11 In our study, acute heart injury was the
most common (19 cases, 95%), followed by ARDS (12 cases, 60%), shock
(12 cases, 60%), and pneumothorax (2 cases, 10%). A study of mild
disease COVID-19 patients in Wuhan reported that 53% of patients in
their cohort died of respiratory failure, 7% died of shock (probably
caused by fulminant myocarditis), and 33% of patients died of both
conditions.21 In our study, the 10 patients in the
death group were all complicated with shock and ARDS. The probability of
death and ARDS in the death group was much higher than that in the
survival group. Due to the limited sample size, this study failed to
show the association of concurrent ARDS or shock with the death of
patients. We speculate that concurrent ARDS and shock may be related to
the death of severe COVID-19 patients. Due to the limitation of sample
size and lack of laboratory data, our study found that only increased
BMI and decreased lymphocyte count were significantly associated with an
increased chance of death in patients with COVID-19 in the ICU.
This study had several limitations. Firstly, the study was conducted in
a single center and was limited by the time of follow-up. Only 20
patients with serious and critical COVID-19 disease patients were
included. Smaller sample size may reduce the reliability of the
statistical analysis. Secondly, there was a lack of detailed medical and
treatment information during the hospitalization of patients, such as
mechanical ventilation parameters, blood gases, patient medication,
imaging examinations, and other supportive treatments. Finally, this is
a retrospective study that failed to include adequate laboratory tests
on all patients, including interleukin 6, serum ferritin, etc.,
resulting in an inability to assess their role in predicting hospital
deaths. The findings of our study can be utilized by future studies to
further investigate the clinical course and outcome of COVID-19 patients
hospitalized in ICU. However, a prospective multicenter study with a
larger sample size is necessitated to further explore the factors
associated with nosocomial death in severe COVID-19 patients.