Assessment and management of the SARS-CoV-2 infection: A secondary
center experience
Abstract
Background: The aim of the study was to evaluate the management and
outcomes of the patients with severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) in a secondary hospital.
Methods: A total of 699 hospitalized patients who had positive rRT-PCR
for SARS-CoV-2 and/or typical findings of COVID-19 at chest computed
tomography (CT) were enrolled in this study. Demographics, comorbities,
initial laboratory tests on admission, treatment modalities,
complications and outcomes were evaluated retrospectively.
Results: The mean age was 57.0±15.6 (range:16-94 years), and male:female
ratio was 1.24. 58.7% of the patients had at least one underlying
comorbidity, the most common was hypertension. 72.8% of the patients
had positive RT-PCR. 18.1% of the patients had lymphopenia, 35.7%
hyperferritinemia, 58.3% increased lactate dehydrogenase, and 58.5%
increased D-dimer. Chest CT revealed moderate and severe stage in 57.9%
of the patients, and bilateral lung involvement in 78.7%.
Hydroxychloroquine was given to 37.2% and favipiravir 67.1% of the
patients.
No
significant difference was observed between treatment groups in terms of
mortality (P=0.487). 5.8% of the patients were transferred to the ICU,
of whom 75.6% were needed non-invasive and 36.5% invasive mechanical
ventilation. The overall case fatality rate was 0.9.
Conclusions: Older age, male sex, low lymphocyte count, CT findings
including bilateral involvement and severe stage were significantly
associated with poor prognosis and mortality.
Key words: COVID-19; SARS-CoV-2; treatment; outcome; adults
Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
has been firstly reported in Wuhan, China, and later World Health
Organization (WHO) designated coronavirus disease 2019 (COVID-19) in
February 20201, declared it as a pandemic on March 11,
2020. Since the first COVID-19 case was confirmed in our country in
March 9, 2020 and first death in March 17, 2020, the burden of the
disease has grown rapidly.
The clinical spectrum of SARS-CoV-2 infection is wide ranging from
asymptomatic infection, mild upper respiratory tract illness, and
pneumonia to life threatening severe disease, even
death.2-5
To our knowledge, no previous studies have been conducted among patients
with COVID-19 in secondary hospitals of our country. Here, we present
clinical assessment, management and outcomes of the patients with
SARS-CoV-2 infection in a secondary hospital.
Material and methods
11,392 real-time reverse transcriptase-polymerase chain reaction
(rRT-PCR) tests were taken from the patients who admitted with
suspicious symptoms or signs of COVID-19 to the emergency department of
a secondary hospital in Istanbul, Turkey between March 31 and May 30,
2020 and September 1 and December 31, 2020. 2448 of rRT-PCR tests were
positive, 8670 were negative and the rest was improper samples. A total
of 699 patients who had positive rRT-PCR for SARS-CoV-2 and/or typical
findings of COVID-19 at chest computed tomography (CT) were hospitalized
and involved in this retrospective observational study. Three wards, a
total of 43 beds, were transformed into clinics of COVID-19 and 6 beds
in intensive care unit (ICU) were reserved for these patients.
Demographics, comorbities, medications, triage vitals, symptoms and
signs on admission, initial laboratory tests, PCR results, inpatient
treatment (antivirals, corticosteroids (CS), antibiotics, convalescent
plasma, tocilizumab), complications (heart failure, septic shock, acute
respiratory distress syndrome) and outcomes (length of hospitalization,
ICU requirement, discharge, readmission, and mortality) were extracted
retrospectively from electronic medical records.
Oropharyngeal and nasopharyngeal swab samples were taken from all of the
patients at the emergency department before hospitalization and were
transferred to laboratory authorized by the Ministry of Health Public
Health Office. rRT-PCR tests for SARS-CoV-2 were performed by using
Biospeedy COVID-19 RT-qPCR Detection Kits (Bioksen, Istanbul, Turkey).
All of the patients had routine blood examinations as complete blood
count, biochemical tests (liver and renal function tests, glucose,
electrolytes), lactate dehydrogenase (LDH), C-reactive protein (CRP),
ferritin, D-dimer on admission. Cardiac enzymes, procalcitonin (PCT) and
fibrinogen were tested if clinically indicated. Chest CT scan was also
performed in every patient on admission.
Diagnosis of COVID- 19 disease was based on the WHO guidance6 and the New Coronavirus Pneumonia Prevention and
Control Program (fifth edition) published by the National Health
Commission of China.7 Acccording to clinical features
on admission, the patients were classified as mild, moderate, severe and
critical cases. Mild patients refer to patients with no radiographic
evidence of pneumonia and moderate patients were the patients with
fever, respiratory symptoms, and radiographic evidence of pneumonia. The
patients who had respiratory distress (≥ 30 breaths), ≤ 93% oxygen
saturation at rest, ratio of partial pressure of arterial oxygen to
fractional concentration of oxygen inspired air ≤ 300 mm Hg or and/or
lung infiltrates > 50% within 24-48 hours defined as
having severe disease whereas if the patients had complications such as
respiratory failure, requirement of mechanical ventilation support,
septic shock, and multiple organ failure were defined as critical
cases.7
Multiple ground-glass opacities and consalidations were considered
typical for COVID-19. CT findings were classified as; 0: Normal, 1: Mild
(ground-glass opacity and consolidation, lesions can be single or
multiple and may de located in both lung lobes), 2: Moderate (large
lesions in more than one lobe in both lungs, various sizes of
consolidation and fibrosis), 3: Severe (lesions are diffuse in both
lungs and in different density, white lung sign due to involvement of
large areas of lung, thickening of pleura, and pleural
effusion).8
The patients were followed-up by pulse oximetry monitoring. The patients
whose oxygen saturation rate was ≤ 93% were given oxygen support by
nasal cannula or face masks. The standart treatment protocol recommended
by National Ministry of Health Public Health Office included oral
oseltamivir (Tamiflu®) 2x75 mg/day due to inability to
rule out seasonal influenza, oral hydroxychloroquine
(Plaquenil®) 2x400 mg loading dose and 2x200 mg/day
maintenance dose and oral azithromycin 1x500 loading dose and 1x250
mg/day maintenance dose for 5 days during the first wave of the
outbreak.9 Routine electrocardiography was performed
before the initiation of treatment to rule out QT interval prolongation.
If no improvement was observed, oral favipiravir or lopinavir 200
mg/ritonavir 50 mg (Kaletra®) 2x2 was initiated.
Favipiravir (Favicovir®) was given at a loading dose
2x1600 mg and 2x600 mg/day maintenance dose, and especially was
preferred in the second wave of the outbreak. Cephalosporins or
piperacillin-tazobactam and with or without respiratory fluoroquinolones
were given for possible bacterial agents, if indicated. Additionally,
vitamin C (1x3 gr) was used.
Later in the outbreak, low molecular weight heparin (LMWH), as
Enoxaparin, was started according to body mass index (BMI<
40/kg/m2 1x40 mg/day, and BMI > 40/kg/m2 2x40 mg/day
subcutaneously) to prevent venous thromboembolism. If creatinine
clearance (CrCl)< 30 ml/min, standart dose heparin (5000 U 2x1
or 3x1/day, subcutaneously) was recommended by National Ministry of
Health guidelines. Methylprednisolone 40-80 mg/day intravenously was
also added to the treatment protocol. Some patients who had worsening
symptoms and laboratory parameters despite treatment with low-moderate
dose CS were given pulse methylprednisolone 250 mg/day for three
consecutive days. If no response was observed with CS and signs of
macrophage activation syndrome (MAS) including persistent fever,
continuously increasing CRP, ferritin (> 700 μg/L), and
D-dimer levels, lymphopenia, thrombocytopenia, neutrophilia and
deterioration of liver function tests were detected, tocilizumab
(Actemra®) 1x200-400 mg was administered.
Convalescent
plasma was given in patients within 7 days before pneumonia progresses.
The patients who clinically decompensated (tachypnea respiratory
rate>30/min, dyspnea, refractory hypoxemia, hypotension )
and had decreased oxygen saturation rate (<90%) despite
treatment, oxygen support, and prone positioning were transffered to
ICU.
The criteria for discharge were absence of fever at least 3 days,
clinical remission of respiratory and other
symptoms.10
The case fatality rate (CFR) was defined as number of deaths who tested
positive for SARS-CoV-2 divided by the number of laboratory-confirmed
SARS-CoV-2 cases admitted to hospital.11
The study protocol was approved by the local ethics committee
(No:2/2021.K-08). This study was performed in accordance with the
declaration of Helsinki. Written informed concents were taken from
patients before treatment.
Statistical analysis
Statistical analysis was performed using SPSS 15.0 software (SPSS Inc,
Chicago,IL,U.S.A.). Results were expressed as numbers and percentage for
categorical variables and means ± SD, minimum and maximum for numerical
variables. The analysis was conducted using chi-square test. As the
numerical variables did not meet the normal distribution, comparisons of
two independent groups were made by using Mann Whitney U test. Pvalues of <0.05 were considered statistically significant.
Results
The mean age of 699 patients was 57.0±15.6 (range:16-94 years), and
male:female ratio was 1.24. The median duration of hospitalization was
6.4±4.8 days, significantly higher in patients with both diabetes
mellitus (DM) and hypertension (HT) than the other patients (P=0.003).
Overall, 58.7% of the patients had at least one underlying comorbidity.
The most common comorbidity was HT, followed by DM, cardiovascular
disease, asthma and chronic obstructive pulmonary disease (COPD). The
most common symptoms on admission were cough (49.8%), fever (32.5%),
and dyspnea (32%). The clinical and demographic characteristics of the
patients are shown in Table 1.
72.8% of the patients had positive RT-PCR. Positivity was significantly
higher in the patients hospitalized in the second wave than the patients
in the first wave of the outbreak (80.7% vs 57.5%, P<0.001).
18.1% of the patients had lymphopenia, 35.7% hyperferritinemia, 58.3%
increased LDH, 1.9% thrombocytopenia, 58.5% increased D-dimer, 45.5%
increased PCT and 22.9% hyponatremia. The laboratory findings of the
patients are shown in Table 2.
When compared, no statistically significant differences were obtained in
terms of complete blood count, biochemical parameters, and CT findings
among patients according to age, sex, and underlying comorbidity except
increased PCT levels in patients with DM and both DM and HT. There was
no difference in laboratory findings between the patients hospitalized
in the first and second waves.
Chest CT classification and distribution of lesions were significantly
different in patients hospitalized in the first wave of the outbreak
than the patients in the second wave (P<0.001). Moderate and
severe stage, and bilateral lung involvement were higher in patients
hospitalized in the second wave (P<0.001).
26.6% of the patients whose RT-PCR tests were negative, but had CT
findings suggesting COVID-19 disease were accepted to be infected and
given treatment. The combination of hydroxychloroquine, azithromycin and
oseltamivir treatment was given 20.2% of the patients, whereas 31.2%
of the patients received hydroxychloroquine plus azithromycin treatment
in the first wave (Table 3). All of the patients (n= 426) were given
favipiravir monotherapy in the second wave. Antibiotics other than
azithromycin were used in 41.9% of the patients, in 43.3% of the
patients treated with hydroxychloroquine and 46.7% of the patients
treated with favipiravir. No significant difference was observed between
treatment groups, hydroxychloroquine and favipiravir in terms of
mortality (2.3% vs 3.3%, P=0.487).
1.49% of the patients who received favipiravir developed bradycardia
responsive to atropine. Only 3 patients had rash due to drug side effect
or disease itself.
51.9% of the patients were treated with CS. Only two patients received
pulse steroids. No significant difference was observed in mortality
between patients who received CS, predominantly in the second wave, and
those who did not (P=0.487).
Tocilizumab was given to 5.7% (n=40) of the patients, all in the second
wave. 60% of these patients were discharged, 37.5% (n=15) were
transferred to our ICU, and 25% were transferred to another ICU due to
lack of beds in ICU or advanced care. 33.3% (n=5) of our patients in
ICU underwent invasive mechanical ventilation (IMV), 93.3% non-invasive
ventilation (NIV) and 40% of them died. 80% of the patients treated
with tocilizumab developed elevated liver enzymes up to five times upper
normal limits, gradually returning to normal levels during follow-up.
Convalescent plasma was given to 6 patients, of whom 50% died.
5.8% of the patients (n=41) were transferred to the ICU. 68.2% of
these patients were male and the mean age was 63.3±12.3. NIV was
required in 75.6% of the patients in the ICU, whereas 36.5% of the
patients underwent IMV. The patients in ICU had predominantly HT and DM
(only HT in 4 patients, only DM in 2, and both HT and DM in 14). Only 7
patients had asthma and/or COPD. 34.1% of ICU patients had no
underlying comorbidity.
The overall mortality rate was 3.7 and 42.8% in our ICU. Respiratory
failure was the most common complication, followed by cardiac arrest in
ICU. The median time from hospitalization to death was 6.04±4.08 day,
and was not significantly different from survivors. None of the patient
survived among patients who underwent IMV. Older age, male sex, low
lymphocyte count, CT findings including bilateral involvement and severe
stage, and the need for IMVwere associated with poor prognosis (P=0.047,
P=0.048, P=0.029, P=0.047, P<0.001, and P<0.001,
respectively).
92.4% of our patients were discharged, only 1.5% (n=10) of them with
oxygen concentrator. During the study period 2.4% of the patients, and
16.6% of the patients in ICU were transferred to other ICUs in the city
due to lack of beds or more advanced care. Six patients with leukemoid
reaction were referred to the hematology outpatient clinic, and one of
them was diagnosed as chronic myeloid leukemia. Follow-up after
discharge from the electronic health records, which includes all
inpatient and outpatient visits of the patients, was revealed that only
8 patients (5 in other hospitals and 3 at home) have been died. The rate
of readmission within 30 days was 1.28.
2% of the patients were health-care workers, of whom 13 had positive
RT-PCR and one had negative. One of them died in the tertiary hospital
where he was transffered.
Discussion
Previously reported studies among patients with COVID-19 have stated
predominance of older age and male sex, particularly in hospitalized
patients. 2,4,5,12-22 Similarly, 55.5% of our
patients were male and the median age was 57.
Older age, male sex and comorbidities were significantly associated with
the severity of the disease and mortality.2,4,5,13-23It has been reported that 13-73.4% of the patients had
comorbidities.13-15,23 58.7% of our patients had at
least one accompanying comorbidity. The most common one was HT in our
study, compatible with the other studies,3,4,12,13,18,20,24 followed by DM,3,5,12,13,19,20 and cardiovascular
diseases.5 Obesity was one of the comorbidities
reported to affect disease severity and
mortality,4,5,20 but could not be determined in this
retrospective study. The incidence of COPD and asthma was lower in our
patients (5.9% and 8.9%, respectively), as in the other studies.2-5,12,18,26
Fever and cough were frequently reported initial symptoms2-4,12,19,20,25,26, similarly the most common
presenting symptom was cough in this study. Dyspnea on admission was
observed in 32% of our patients, as mentioned in other studies.4,12,15,26
Elevated CRP, ferritin, D-dimer, and PCT were indicators of poor
prognosis.2-5,17,20,24 Lymphopenia due to viral
particle-induced cytoplasmic damage and apoptosis was also correlated
with severity of disease and mortality. 2-4,20,23,27Wang et al. 15 showed that median lymphocyte count
≤800 cell/µL was predictive for severity of the disease and decreased
gradually as the disease progress and increased with recovery. In our
study, we observed that 18.1% of the patients had lymphopenia on
admission, mostly associated with severe disease, and continue to
decrease as the disease progressed, improved gradually in survivors, but
remained low in non-survivors.
Mo et al. 16 reported that besides increased CRP and
LDH levels, thrombocytopenia, low level of albumin, elevated neutrophil
and AST were also correlated with poor prognosis, in contrast we did not
observe significant differences in these parameters among patients
according to disease severity, treatment modality, and mortality.
Increased level of troponin 4,5,10,24 and progressive
elevation of PCT 23, particularly in patients with
critical disease were related with poor
prognosis.4,5,10,24 Significantly higher levels of PCT
were observed in our patients with DM and both DM and HT due to high
inflammatory response, not secondary bacterial infection, but this was
not associated with mortality.
It has been stated that CT is more reliable than RT-PCR testing due to
false negative results. 3,28 When compared, Ai et al.28 reported higher sensitivity of chest CT for
diagnosis of COVID-19 than reported by Guan et al.3(97% versus 86.2%). Thus, CT was performed in all of our patients on
admission.
Mo et al.16 and Feng et al. 24reported that increased incidence of bilateral pneumonia and pleural
effusion associated with severity of disease and poor prognosis. Chest
CT revealed that 78.7% of our patients had bilateral lung involvement
and 57.9% of them had moderate and severe stage. Only two patient had
pleural effusion which was regressed with treatment.
Currently, no effective proven antiviral treatment for patients with
COVID-19 has been identified. Wang et al. 29demonstrated that chloroquine takes part at both entry, and at
post-entry stages of the SARS-CoV-2 virus in Vero E6 cells, by
increasing endosomal pH required for virus/cell fusion, as well as
interfering with the glycosylation of cellular receptors of SARS-CoV.
Although Food and Drug Administration (FDA) cautions against use of
hydroxychloroquine due to arrhythmias, Satarker et al.30 stated that hydroxychloroquine plus azithromycin
can reduce viral load, and Bhandari et al. 12 observed
early recovery with hydroxychloroquine without effectively influencing
the overall mortality. The researchers who predominantly preferred
hydroxychloroquine treatment 2,11,12,20, reported the
rate of mortality as 21%, 2.8%, 20% and 21.2%, respectively. We used
hydroxychloroquine plus azithromycin combination in the first wave of
the outbreak, and favipiravir, RNA polymerase inhibitor, in the second
wave. 31 Although no statistically significant
difference was observed in terms of mortality between treatment groups
in this study, it was slightly higher in the group treated with
favipiravir (3.3% vs 2.3%), may be explained by the fact that the
patients who had more severe disease were hospitalized in the second
wave when compared with the first wave due to the change in
hospitalization criteria according to National Ministry of Health
guidelines.
Antibiotics other than azithromycin for possible bacterial infections
were used in 41.9% of our patients, similarly reported by Ersan et
al.27 and lower than the other studies 58-100%.2,3,23-25,27
Many guidelines and reports stated that CS were contraindicated or not
recommended due to the complications including prolonged viremia,
hyperglycemia, avascular necrosis, bacterial superinfections, and
psychosis.32-34 Increased risk of disease progression,
increased use of antibiotics, prolonged duration fever and length of
hospital stay were also reported. 33 Some researchers
proposed that the use of CS treatment was not significantly associated
with mortality 32,33, while according to the others,
early CS might reduce inflammatory response, and prevented the
progression of COVID-19 disease. 35,36
Chinese Thoracic Society have developed an expert consensus statement on
the use of corticosteroids in 2019-nCoV pneumonia, and stated that CS
should be given low-to-moderate doses (≤0·5–1 mg/kg per day
methylprednisolone or equivalent) for ≤7 days.37 Li et
al. 36 observed no difference between patients who
were given low-dose ( < 2 mg/kg) and high-dose (
>2 mg/kg) CS. 51.9% of our patients, particularly in the
second wave of outbreak were given CS. No side effect was observed with
CS treatment other than hypergycemia in this study.
Tocilizumab, anti-interleukin-6 receptor monoclonal antibody, proposed
to reduce progression of the disease and the need for noninvasive or
invasive mechanical ventilation or death in hospitalized patients with
Covid-19 pneumonia, but it did not improve survival.38,39 Gupta et al. 40 reported that
the risk of mortality was lower in critically ill patients treated with
tocilizumab in the first 2 days of ICU admission compared with those who
did not. 5.7 % of the patients received tocilizumab, of whom 37.5%
were transferred to ICU, 60% were discharged and 40% died. In our
opinion, tocilizumab reduces the progression of the disease, the need
for ICU and IMV.
Hyperinflammatory response to virus, hypoxia and prolonged
immobilization carry a high risk of thromboembolic events. Thus, all of
our patients were given LMWH in the second wave of the outbreak, as
Casas-Rojo et al. used LMWH at prophylactic doses in 83.4 % of their
patients.2 Although the mortality did not
significantly changed when the first and second waves were compared, we
think that the treatment with LMWH and CS reduced the mortality rate.
The cytokine storm, excessive production of pro-inflammatory cytokines,
is considered responsible for the progression of the disease and
mortality. The rate of patients who needed intensive care has been
reported to be 5-15.7% in different studies.2,3,18,22,25,41,42 Mortality varies from 2.08% to
78% in patients with COVID-19 disease12,14,15,21,24,41,42, and from 1.4% to 72% among ICU
patients with COVID-19. 3,4,16,17,27 In the studies
conducted in our country, mortality rates between 2.08 and 10.5%26,27,41,42 have been reported. 5.8% of our patients
were transffered to ICU and 36.5% of them underwent IMV. The overall
CFR was 0.9 in this study, and the mortality rate was 42.8% in our ICU.
Approximately 50% of the patients in ICU had HT and DM. Strikingly, one
third of these patients had no underlying comorbidity.
Older age, male sex, low lymphocyte count, CT findings including
bilateral involvement and severe stage were associated with poor
prognosis in this study. The most common complication was acute
respiratory failure, compatible with the other
studies.2,12
Median hospital lenght of stay ranged from 4 to 53 days within China,
and 4 to 21 days outside of China. 43 The duration of
hospitalization was important for predicting the average lenght of
hospital stay and planning the capacity. The treated patients were
discharged to be followed-up in an outpatient setting, and the patients
who still need oxygen were discharged with oxygen concentrator for
meeting increased bed need. Thus, the median duration of hospitalization
was 6.4±4.8 days in this study, lower than the other studies.12,15,22,24,26,27 Limitations of the study were being
a single-center retrospective study, lack of smoking history, failure to
record the oxygen saturation rate on admission at emergency department,
inability to detect other common viruses (Influenza A and B, RSV,
Adenovirus), inability to calculate BMI due to workload and urgent start
of the supportive treatment, and inavailability of remdesivir in our
country.
All of the health institutions in our country, without distinction of
secondary or tertiary hospital worked mandatorily as a pandemic hospital
during pandemic. Although studies from tertiary health institutions of
our country are available in literature, this study is the first
presenting data from a secondary hospital. Besides infectious disease
and internal medicine doctors, other doctors from various clinics and
nursing staff worked with great devotion on a voluntary basis in the
follow-up and management of the patients with COVID-19. In our opinion,
this voluntarism and cooperation was of great importance in the fact
that hospitalization periods were short and the mortality rates were
similar to those higher level tertiary hospitals.
References
- World Health Organization. (2020). Novel Coronavirus (2019-nCoV):
situation report, 22. World Health
Organization. https://apps.who.int/iris/handle/10665/330991)
- Casas-Rojo JM, Antón-Santos JM, Millán-Núñez-Cortés J, et al; en
nombre del Grupo SEMI-COVID-19, Network. Clinical characteristics of
patients hospitalized with COVID-19 in Spain: results from the
SEMI-COVID-19 Registry. Rev Clin Esp (Barc). 2020;220(8):480–94. doi:
10.1016/j.rceng.2020.07.003.
- Guan W, Ni Z, Hu Yu, Liang W, Ou C, He J. Clinical Characteristics of
Coronavirus Disease 2019 in China. N Engl J Med 2020;382:1708-1720.
doi:10.1056/ NEJMoa2002032
- Borobia AM, Carcas AJ, Arnalich F, et al, On Behalf Of The Covid Hulp
Working Group. A Cohort of Patients with COVID-19 in a Major Teaching
Hospital in Europe. J Clin Med. 2020;9(6):1733. doi:
10.3390/jcm9061733.
- Petrilli CM, Jones SA, Yang J, et al. Factors associated with hospital
admission and critical illness among 5279 people with coronavirus
disease 2019 in New York City: prospective cohort study. BMJ.
2020;369:m1966. doi: 10.1136/bmj.m1966.
- WHO: Clinical management of severe acute respiratory infection when
novel coronavirus (2019-nCoV) infection is suspected:interim guidance.
January 28, 2020. https://www.who.
int/docs/default-source/coronaviruse/clinical-management-of-
novel-cov.pdf. Accessed Feb 15, 2020.
- National Health Commission of China: New corona virus pneumonia
prevention and control program, 5th Ed., 2020.
Availableat:http://www.nhc.gov.cn/jkj/s3577/202002/
a5d6f7b8c48c451c87dba14889b30147/files/3514cb996ae24e2faf65953b4ecd0df4.pdf.
Accessed February 21, 2020.
- Saeed GA, Gaba W, Shah A, et al. Correlation between Chest CT Severity
Scores and the Clinical Parameters of Adult Patients with COVID-19
Pneumonia. Radiol Res Pract. 2021;2021:6697677.
doi:10.1155/2021/6697677
- Republic of Turkey Ministry of Health Directorate General of Public
Health (2020). 8 COVID-19 (SARS-CoV-2 Infection) Guide (in Turkish)
[online]. Website 9
https://covid19bilgi.saglik.gov.tr/depo/rehberler/COVID-19_Rehberi.pdf.
[accessed 10 14 April 2020].
- Zhou F, Yu T, Du R, et al. Clinical course and risk factors for
mortality of adult inpatients with COVID-19 in Wuhan, China: a
retrospective cohort study. Lancet. 2020;395(10229):1054-1062. doi:
10.1016/S0140-6736(20)30566-3.
- Jiménez E, Fontán-Vela M, Valencia J, et al.; COVID@HUIL Working
Group; COVID@HUIL Working Group. Characteristics, complications and
outcomes among 1549 patients hospitalised with COVID-19 in a secondary
hospital in Madrid, Spain: a retrospective case series study. BMJ
Open. 2020;10(11):e042398. doi: 10.1136/bmjopen-2020-042398. PMID:
33172949; PMCID: PMC7656887.
- Bhandari S, Singh A, Sharma R, et al. Characteristics, Treatment
Outcomes and Role of Hydroxychloroquine among 522 COVID-19
hospitalized patients in Jaipur City: An Epidemio-Clinical Study. J
Assoc Physicians India. 2020;68(6):13-19. PMID: 32610873.
- Iaccarino G, Grassi G, Borghi C, Ferri C, Salvetti M, Volpe M;
SARS-RAS Investigators. Age and Multimorbidity Predict Death Among
COVID-19 Patients: Results of the SARS-RAS Study of the Italian
Society of Hypertension. Hypertension. 2020;76(2):366-372. doi:
10.1161/HYPERTENSIONAHA.120.15324.
- Grasselli G, Zangrillo A, Zanella A, et al.; COVID-19 Lombardy ICU
Network. Baseline Characteristics and Outcomes of 1591 Patients
Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region,
Italy. JAMA. 2020;323(16):1574-1581. doi: 10.1001/jama.2020.5394.
- Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138
Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia
in Wuhan, China. JAMA. 2020;323(11):1061-1069. doi:
10.1001/jama.2020.1585.
- Mo P, Xing Y, Xiao Y, et al. Clinical characteristics of refractory
COVID-19 pneumonia in Wuhan, China. Clin Infect Dis. 2020;ciaa270.
doi: 10.1093/cid/ciaa270.
- Huang
I, Pranata R, Lim MA, Oehadian A, Alisjahbana B. C-reactive protein,
procalcitonin, D-dimer, and ferritin in severe coronavirus
disease-2019: a meta-analysis. Ther Adv Respir Dis.
2020;14:1753466620937175. doi: 10.1177/1753466620937175.
- Ozger HS, Aysert Yildiz P, Gaygisiz U, et al. The factors predicting
pneumonia in COVID-19 patients: preliminary results from a university
hospital in Turkey. Turk J Med Sci. 2020;50(8):1810-1816. doi:
10.3906/sag-2005-385.
- Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its
effects in patients infected with SARS-CoV-2: a systematic review and
meta-analysis. Int J Infect Dis. 2020;94:91-95. doi:
10.1016/j.ijid.2020.03.017.
- Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of
SARS-CoV-2 infection-a review of immune changes in patients with viral
pneumonia. Emerg Microbes Infect. 2020;9(1):727-732. doi:
10.1080/22221751.2020.1746199.
- Hafiz M, Icksan AG, Harlivasari AD, Aulia R, Susanti F, Eldinia L.
Clinical, Radiological Features and Outcome of COVID-19 patients in a
Secondary Hospital in Jakarta, Indonesia. J Infect Dev Ctries.
2020;14(7):750-757. doi: 10.3855/jidc.12911. PMID: 32794466.
- Giesen C, Diez-Izquierdo L, Saa-Requejo CM, et al.; COVID
Epidemiological Surveillance and Control Study Group. Epidemiological
characteristics of the COVID-19 outbreak in a secondary hospital in
Spain. Am J Infect Control. 2020;S0196-6553(20)30700-8. doi:
10.1016/j.ajic.2020.07.014.
- Huang C, Wang Y, Li X, et al. Clinical features of patients infected
with 2019 novel coronavirus in Wuhan, China. Lancet.
2020;395:497–506.
- Feng Y, Ling Y, Bai T, et al. COVID-19 with Different Severities: A
Multicenter Study of Clinical Features. Am J Respir Crit Care Med.
2020;201(11):1380-1388. doi: 10.1164/rccm.202002-0445OC.
- Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically
ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a
single-centered, retrospective, observational study. Lancet Respir
Med. 2020;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5.
- Acar HC, Can G, Karaali R, et al. An easy-to-use nomogram for
predicting in-hospital mortality risk in COVID-19: a retrospective
cohort study in a university hospital. BMC Infect Dis. 2021;21(1):148.
doi: 10.1186/s12879-021-05845-x.
- Ersan G, Akkiraz Baç G, Yüksel Ö, et al. The Demographic and Clinical
Features of 479 COVID-19 Patients: A Single-center Experience.
Mediterr J Infect Microb Antimicrob. 2020;9:9.
- Ai T, Yang Z, Hou H, et al. Correlation of Chest CT and RT-PCR Testing
for Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014
Cases. Radiology. 2020;296(2):E32-E40. doi: 10.1148/radiol.2020200642.
- Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively
inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro.
Cell Res. 2020;30(3):269-271. doi: 10.1038/s41422-020-0282-0.
- Satarker S, Ahuja T, Banerjee M, E VB, Dogra S, Agarwal T, Nampoothiri
M. Hydroxychloroquine in COVID-19: Potential Mechanism of Action
Against SARS-CoV-2. Curr Pharmacol Rep. 2020;1-9. doi:
10.1007/s40495-020-00231-8.
- Republic of Turkey Ministry of Health Directorate General of Public
Health (2020). COVID-19 (SARS-CoV-2 Infection) Guide (in Turkish)
[online].
https://covid19.saglik.gov.tr/TR-66926/eriskin-hasta-tedavisi.html.
[accessed 12 October 2020].
- Russell CD, Millar JE, Baillie JK. Clinical evidence does not support
corticosteroid treatment for 2019-nCoV lung injury. Lancet.
2020;395(10223):473-475. doi: 10.1016/S0140-6736(20)30317-2.
- Li Q, Li W, Jin Y, et al. Efficacy Evaluation of Early, Low-Dose,
Short-Term Corticosteroids in Adults Hospitalized with Non-Severe
COVID-19 Pneumonia: A Retrospective Cohort Study. Infect Dis
Ther 2020;9: 823–836.
https://doi.org/10.1007/s40121-020-00332-3.
- Mattos-Silva P, Felix NS, Silva PL, et al. Pros and cons of
corticosteroid therapy for COVID-19 patients. Respir Physiol
Neurobiol. 2020;280:103492. doi: 10.1016/j.resp.2020.103492.
- RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M,
Bell JL, Linsell L, et al. Dexamethasone in Hospitalized Patients with
Covid-19 - Preliminary Report. N Engl J Med. 2020;NEJMoa2021436. doi:
10.1056/NEJMoa2021436.
- Liu F, Ji C, Luo J, et al. Clinical characteristics and
corticosteroids application of different clinical types in patients
with corona virus disease 2019. Sci Rep. 2020;10(1):13689. doi:
10.1038/s41598-020-70387-2.
- Zhao JP, Hu Y, Du RH, et al. [Expert consensus on the use of
corticosteroid in patients with 2019-nCoV pneumonia]. Zhonghua Jie
He He Hu Xi Za Zhi. 2020;43(3):183-184 doi:
10.3760/cma.j.issn.1001-0939.2020.03.008.
- Salama C, Han J, Yau L, et al. Tocilizumab in Patients Hospitalized
with Covid-19 Pneumonia. N Engl J Med. 2021;384(1):20-30. doi:
10.1056/NEJMoa2030340.
- Hermine O, Mariette X, Tharaux PL, Resche-Rigon M, Porcher R, Ravaud
P; CORIMUNO-19 Collaborative Group. Effect of Tocilizumab vs Usual
Care in Adults Hospitalized With COVID-19 and Moderate or Severe
Pneumonia: A Randomized Clinical Trial. JAMA Intern Med.
2021;181(1):32-40. doi: 10.1001/jamainternmed.2020.6820.
- Gupta S, Wang W, Hayek SS, et al; STOP-COVID Investigators.
Association Between Early Treatment With Tocilizumab and Mortality
Among Critically Ill Patients With COVID-19. JAMA Intern Med.
2021;181(1):41-51. doi: 10.1001/jamainternmed.2020.6252.
- Calik Basaran N, Uyaroğlu OA, Telli Dizman G, et al. Outcome of
Non-Critical COVID-19 Patients with Early Hospitalization and Early
Antiviral Treatment Outside the ICU. Turk J Med Sci. 2020 doi:
10.3906/sag-2006-173. Epub ahead of print.
- Satici C, Demirkol MA, Sargin Altunok E, et al. Performance of
pneumonia severity index and CURB-65 in predicting 30-day mortality in
patients with COVID-19. Int J Infect Dis. 2020;98:84-89. doi:
10.1016/j.ijid.2020.06.038.
- Rees EM, Nightingale ES, Jafari Y, et al. COVID-19 length of hospital
stay: a systematic review and data synthesis. BMC Med. 2020;18(1):270.
doi: 10.1186/s12916-020-01726-3.
Table 1. The demographic and clinical characteristics of the patients on
admission
Age (years; mean ± SD) 57.0±15.6 (16-94)
Gender (male/female) 1.24 (388/311)
Duration of disease (days; mean ± SD) 6.4±4.8
Concomitant chronic diseases n, (%) 410 (58.7%)
Hypertension 301 (43.1%)
Diabetes mellitus 126 (18%)
Cardiovascular disease ( ischemic heart 65 (9.2%)
disease, congestive heart disease)
Asthma 62 (8.9%)
COPD 41 (5.9%)
Malignancy 8 (1.1%)
Chronic renal disease 16 (2.3%)
Cerebrovascular disease 12 (1.7%)
Infections (Hepatitis B, C) 3 (0.4%)
Others (Behçet disease, Celiac disease, 14 (2%)
ulcerative colitis,epilepsy, romatoid arthritis)
Signs and symptoms n, (%)
Fever ( temperature ≥37.3°C) 227 (32.5%)
Fatigue 149 (21.3%)
Sore throat 22 (3.1%)
Cough 348 (49.8%)
Dyspnea 224 (32%)
Nausea/vomiting 56 (8%)
Diarrhea 13 (1.9%)
Myalgia 74 (10.6%)
Headache 36 (5.2%)
Anosmia and ageusia 14 (2%)
Disease severity
Mild 0
Moderate 587 (83.9%)
Severe 112 (16%)
Critical 0
Chest CT imaging n, (%)
Normal 64 (9.2%)
Mild 230 (32.9%)
Moderate 294 (42.1%)
Severe 111 (15.9%)
Pleural effusion 2 (0.28%)
Pericardial effusion 1 (0.14%)
Lesion distribution n, (%)
Unilateral 85 (12.2%)
Bilateral 550 (78.7%)
RT-PCR n, (%)
Positive 509 (72.8%)
Negative 190 (27.1%)
COPD= Chronic obstructive pulmonary disease; RT-PCR=
Reverse-transcription polymerase chain reaction;
Table 2. The laboratory findings of the patients on admission
Hemoglobin ( 110-160 g/L) 13.4±1.7 (7.7-18.3)
White blood cell count (4-10 x103 µL) 7373.2±3592.2
(580-36700)
Platelet count (100-300 x103 µL) 224.5±90.0 (21-774)
Lymphocyte count (0.8-4.0 x103 µL) 1388.2±695.4
(0-5670)
CRP (0-5 mg/L) 58.4±69.1 (0-359.3)
LDH (135-225 IU/L) 268.0±106.6 (20-956)
Ferritin (30-400 mcg/L) 400.0±383.6 (10.9-2639)
D-dimer (0-500 µg/ml) 848.9±1311.5 (0-21900)
Glucose (74-109 mg/dL) 139.7±70.7 (25-856)
Urea (10-50 mg/dl) 36.1±20.5 (8-195)
Creatinine (0.7-1.2 mg/dL) 1.03±3.58 (0.01-2.91)
ALT (0-41 IU/L) 31.5±29.5 (3-318)
AST (0-50 IU/L) 33.7±30.3 (10-492)
Sodium (136-145 mmol/L) 139.7±47.2 (121-163)
Potassium (3.5-5.5 mmol/L) 4.26±0.49 (2.7-6.17)
Albumin (35-52 g/L) 31.7±4.0 (18.4-44.7)
Fibrinogen (2-4 g/L) 5.38±1.24 (2.28-7.59)
Procalcitonin (0-0.12 ng/ml)
0.31±0.73
(0-5.11)
Troponin (0-0.014 ng/ml) 1.48±7.26 (0-60.7)
ALT=Alanine aminotransferase; AST=Aspartate aminotransferase; CRP=
C-reactive protein; LDH= lactate dehydrogenase
Table 3. Treatments and clinical outcomes of the patients
Antiviral treatment n, (%)
Oseltamivir 141 (20.2%)
Favipiravir 469 (67.1%)
Lopinavir/ritonavir 11 (1.6%)
Hydroxychloroquine n, (%) 260 (37.2%)
Azithromycin n, (%) 218 (31.2%)
Intravenous antibiotics n, (%) 293 (41.9%)
Systemic glucocorticoids n, (%) 363 (51.9%)
Anticoagulation (Enoxaparin) n, (%) 543 (77.7%)
Tocilizumab n, (%) 40 (5.7%)
Convalescent plasma n, (%) 6 (0.9%)
Oxygen therapy n, (%) 699 (100%)
Mechanical ventilation n, (%)
Invasive 15 (2.1%)
Non-invasive 31 (4.4%)
Intensive care unit n, (%) 41 (5.8%)
Outcomes n, (%)
Discharge 646 (92.4%)
Discharge from hospital with oxygen 10 (1.5%)
concentrators
Rehospitalization 9 (1.28%)
Death 26 (3.7%)