key: cord-0918358-pfu8azym
authors: Altunok, Elif Sargin; Alkan, Mustafa; Kamat, Sadettin; Demirok, Berna; Satici, Celal; Demirkol, Mustafa Asim; Gursoy, Bengul; Surmeli, Cemile Dilsah; Cengel, Ferhat; Calik, Mustafa; Turkmen, Ulku Aygen
title: Clinical characteristics of adult patients hospitalized with laboratory-confirmed COVID-19 pneumonia
date: 2020-10-23
journal: J Infect Chemother
DOI: 10.1016/j.jiac.2020.10.020
sha: 282d49815f6e3526acf981d3b7bce4beff6f3760
doc_id: 918358
cord_uid: pfu8azym

Background The clinical spectrum of COVID-19 has a great variation from asymptomatic infection to acute respiratory distress syndrome and eventually death. The mortality rates vary across the countries probably due to the heterogeneity in study characteristics and patient cohorts as well as treatment strategies. Therefore, we aimed to summarize the clinical characteristics and outcomes of adult patients hospitalized with laboratory-confirmed COVID-19 pneumonia in Istanbul, Turkey. Methods A total of 722 adult patients with laboratory-confirmed COVID-19 pneumonia were analyzed in this single-center retrospective study between March 15 and May 1, 2020. Results A total of 722 laboratory-confirmed patients with COVID-19 pneumonia were included in the study. There were 235 (32.5%) elderly patients and 487 (67.5%) non-elderly patients. The most common comorbidities were hypertension (251 [34.8%]), diabetes mellitus (198 [27.4%]), and ischemic heart disease (66 [9.1%]). The most common symptoms were cough (512 [70.9%]), followed by fever (226 [31.3%]), and shortness of breath (201 [27.8%]). Lymphocytopenia was present in 29.7% of the patients, leukopenia in 12.2%, and elevated CRP in 48.8%. By the end of May 20, 648 (89.7%) patients had been discharged and 60 (8.5%) patients had died. According to our study, while our overall mortality rate was 8.5%, this rate was 14.5% in elderly patients, and the difference was significant. Conclusions This case series provides characteristics and outcomes of sequentially adult patients hospitalized with laboratory-confirmed COVID-19 pneumonia in Turkey.

Therefore, we aimed to summarize the clinical characteristics and outcomes of 722 adult patients hospitalized with laboratory-confirmed COVID-19 pneumonia in Istanbul, Turkey.

This single-center retrospective study was approved by the Ethics Committee of Istanbul Gaziosmanpasa Training and Research Hospital, and the requirement for written informed consent was waived by our ethics committee. Our hospital has served as a pandemic hospital during the outbreak in Istanbul, Turkey. with COVID-19 pneumonia were included in this retrospective study. All patients were followed up to death or discharge or the end of the study (May 20, 2020).

Demographic, clinical findings, laboratory results, radiological features, treatments (antiviral, antibacterial, systemic corticosteroid, tocilizumab, and respiratory support), and outcomes were obtained from electronic medical records of patients. We divided patients into two groups according to age, as an elderly group (≥65 years old) and non-elderly group (<65 years old). All raw data were initially evaluated by trained physicians. The outcomes were

The CT features that were evaluated included; ground-glass opacities (GGO), consolidation, crazy paving pattern, tree-in-bud sign, air bronchogram, subpleural linear opacity, halo and reversed halo signs. The terms were defined in accordance with the Fleischner Society guidelines (8). The location of the lesion was classified as predominantly central or predominantly peripheral, depending on whether it was found in the inner or outer half of the lung field, respectively. The affected lung and lobes pleural and pericardial effusion, the presence of mediastinal lymphadenopathy (short axis>1cm) and bronchiectasis were also noted.

Disease severity on admission was defined on the basis of COVID-19 Diagnosis and Treatment Guide' published by The Ministry of Health of the Republic of Turkey (9). The patients were categorized into three groups according to their disease severity. The severe illness was defined as the presence of one of the followings: (a) respiratory distress with respiratory frequency ≥30/min; (b) pulse oximeter oxygen saturation at rest <93%; and (c) artery partial pressure of oxygen/inspired oxygen fraction, PaO2/ FiO2) ≤300 mm Hg. Critical illness was defined as the requirement of high flow oxygen or non-invasive or invasive mechanical ventilation. The other patients who did not meet the above criteria were classified as having the non-severe illness.

In Turkey, our treatment options for COVID-19 include Hydroxychloroquine (200 mg every 12 h, orally, 5-10 days), Favipiravir (first day 1600 mg, and then 600 mg every 12 h, orally, for 5-7 gün) and Lopinavir-ritonavir (500 mg twice daily, orally, for 10-14 days). Most patients have received a combination of hidroksiqlorokin and azithromycin (500 mg every 24 h, orally, for 5 days). The severe and critically ill patients were received with Favipiravir or Lopinavir-ritonavir based on the COVID-19 Diagnosis and Treatment Guide' published by

The Ministry of Health of the Republic of Turkey (10). Oseltamivir (75 mg every 12 h, orally, for 5-10 days) was also added to the current treatment during the influenza season. In addition, methylprednisolone for 3-15 days and Tocilizumab were received in seriously ill patients in a cytokine storm.

The data obtained were analyzed using an IBM SPSS Statistics 25 program and checked for suitability for a normal distribution with the Shapiro-Wilk test. Categorical variables were presented as counts and percentages. Continuous variables were presented as mean and standard deviation (SD), otherwise as the median and interquartile range (IQR). Continuous variables if normally distributed were analyzed by independent sample t-test; otherwise, the Mann-Whitney U test was used. All categorical data were analyzed with the chi-square test.

Variables significantly associated with mortality in univariate analysis, analyzed in multivariate logistic regression analysis to determine independent risk factors for mortality. P values <0.05 indicated that the difference was statistically significant. breaths/minute, and 150 (20.8%) had oxygen saturation less than 90%. The median leucocytes count was 6.2 (x10 3 /µL), the neutrophil count was 4.3 (x10 3 /µL), lymphocyte count was 1.3 (x10 3 /µL), C-reactive protein (CRP) was 37.5 (mg/L), procalcitonin was 0.16 (ng/mL), and ferritin was 171 (ng/mL). Lymphocytopenia was present in 29.7% of the patients, leukopenia in 12.2%, and elevated CRP in 48.8% (Table 1) .

At admission, the CT findings of the patients are shown in table 3. Of these 657 patients, 87% of patients had involvement of two or more lobes, 87% of lesions were located mainly in the peripheral zone of the lung. When a single lobe was involved, the right lower lobe was most often affected (13/36 [36%]). The most common CT features were patchy or rounded groundglass opacity (GGO) (51%) and GGO with consolidation (39%). Seventy-three (11%) patients had the crazy-paving pattern, 194 (30%) had subpleural linear opacity. The air bronchogram J o u r n a l P r e -p r o o f sign was visualized in 216 (33%) patients, the halo sign in 131(20%), and the reversed halo sign in 60 (9%). The CT findings and other data are presented in table 3.

Clinical severity assessment of COVID-19 pneumonia was defined in 3 groups. The distribution of clinical severity was 543 (75.2%), 90 (12.5%), and 89 (12.3%) for non-severe, severe, and critical respectively (Table 1) .

There were 235 (32.5%) elderly patients and 487 (67.5%) non-elderly patients. The mean age of elderly patients was 74.5 years (SD, ±7.7; range, 65-108 years), and 109 of 235 (46.4%) elderly patients were male. In elderly patients, 72 (30.6%) patients had only one comorbidity, and 120 (51.1%) patients had more than one comorbidities. The prevalence of more than one comorbidity was significantly higher among elderly patients. The most common comorbidities were hypertension (60.9%), diabetes mellitus (40%), and ischemic heart disease (15.7%). Elderly patients compared to non-elderly patients had higher rates of hypertension, diabetes mellitus, and ischemic heart disease, the difference was statistically significant. The most common symptoms were cough (66.8%), followed by shortness of breath (31.5%), and fever (28.5%). At triage, 30 elderly patients (12.8%) were febrile (>38°C), 11 (4.7%) had a respiratory rate greater than 30 breaths/minute, and 71 (30.2%) had oxygen saturation less than 90%. At admission, elderly patients had less fever and low oxygen saturation was more common. The median leucocytes count was 6.6 (x10 3 /µL), the neutrophil count was 4.5 (x10 3 /µL), lymphocyte count was 1.2 (x10 3 /µL), CRP was 48 (mg/L), procalcitonin was 0.18 (ng/mL), and ferritin was 170 (ng/mL). Lymphocytopenia was present in 32.5% of the patients, leukopenia in 8.9%, and elevated CRP in 55.4%. The distribution of clinical severity was 39 (16.6%), and 46 (19.6%) for severe and, critical respectively which was significantly higher than non-elderly patients (Table 1) .

At admission, 712 of 722 patients were admitted to the ward and 10 patients were admitted to the intensive care unit. At ward, oxygen therapy was applied in 108 (15%) patients with the nasal cannula and 32 (4.4%) patients with face mask at admission ( Table 1) . 79 of 712 patients during the follow up at ward were transferred to ICU. The median duration from the onset of hospitalization to ICU admission was 3 days (IQR, 1.7-6) ( Table 4) . Overall, 89 J o u r n a l P r e -p r o o f (12. 3) patients were admitted to the intensive care unit. In ICU, the number of patients required high flow oxygen support, non-invasive mechanical ventilation, and invasive mechanical ventilation were 19 (2.6%), 10 (1.4%), and 60 (8.3%) respectively (Table 4) .

By the end of May 20, 648 (89.7%) patients had been discharged and 60 (8.5%) patients had died; all other patients were still hospitalized. The median hospital duration was 6 (4-10) days. 12 of 14 patients still being hospitalized are followed up at the ward and 2 at the ICU by the end of May 20 (table 4) . Finally, on the multivariable analysis, older age and elevated CRP remained the significant independent risk factors for death (Table 5) .

At admission, 229 of 235 elderly patients were admitted to the ward and 6 elderly patients were admited to the intensive care unit. At the ward, oxygen therapy was applied in 51(21.7%) patients with the nasal cannula and 14 (6%) patients with face mask at admission ( Table 1 ). 40 of 229 elderly patients during the follow up at ward were transferred to ICU.

The median duration from the onset of hospitalization to ICU admission was 3 days (IQR, 2-6) (Table 4) . Overall, 46 (19.6) patients were admitted to the intensive care unit. In ICU, the number of elderly patients required high flow oxygen support, non-invasive mechanical ventilation, and invasive mechanical ventilation were 13 (5.5%), 3 (1.3%), and 30 (12.8%) respectively (Table 4) .

By the end of May 20, 194 (82.6%) patients had been discharged and 34 (14.5%) patients had died; all other patients were still hospitalized. The median hospital duration was 8 (5-12) days. 6 of 7 patients still being hospitalized are followed up at the ward and 1 patients at the ICU by the end of May 20 (table 4) .

A total of 722 adult patients with laboratory-confirmed COVID-19 pneumonia was analyzed in this single-center retrospective study between March 15 and May 1, 2020. We identified major clinical characteristics, laboratory results, radiological features, and outcomes for the disease. We divided patients into two groups according to age, as the elderly group and nonelderly group. We also identified independent risk factors for mortality. Previous reports described different mortality rates for death in adults who were hospitalized with COVID-19 among countries. Mortality rates in studies reported from China vary between 1.4-12.8 (10-J o u r n a l P r e -p r o o f 12). In the first large case series from the US, mortality rates were reported as 21% (13) . In a study conducted in Italy, the mortality rate in inpatients was reported as 20.6% (14) .

According to our study, while our overall mortality rate was 8.5%, this rate was 14.5% in elderly patients, and the difference was significant. Compared to other countries, these mortality rates were significantly lower than the US and Italy and was similar to data reported from China.

Globally, as 17 June 2020, there have been 8,061,550 confirmed cases of COVID-19, including 440,290 deaths, reported to WHO (4). Although most patients present with mild symptoms that are not life-threatening, the number of deaths is still high owing to the large patients' population. In the previous studies identified several risk factors for death in adults who were hospitalized with COVID-19. In particular, older age, d-dimer levels greater than 1 μg/mL, elevated levels of blood IL-6, high-sensitivity cardiac troponin I, and lactate dehydrogenase and lymphopenia were more commonly seen in severe COVID-19 illness inhospital death (15) . Our study confirmed that increased age was associated with death in patients with COVID-19. In addition, those with hypertension and diabetes mellitus were highly prevalent in this case series, but this was not related to the higher rate of comorbidity in elderly patients.

COVID-19 is a viral disease characterized by decreased lymphocyte count. According to our current information, cytokine storm plays an important role in severe COVID-19 cases.

SARS-CoV-2 is known to mainly affect lymphocytes, especially T lymphocytes, and virus particles induce a cytokine storm in the body, this results in lymphopenia (3, 16). In our study, the absolute value of lymphocytes in most patients decreased (29.7%). However, lymphopenia was not associated with mortality in the analyzes. Among laboratory abnormalities, only elevated CRP remained the significant independent risk factors for death in our study.

Because of the primary involvement of the respiratory system, chest CT is strongly recommended in suspected COVID-19 cases, for initial evaluation. The characteristic patterns and distribution of initial CT manifestations in COVID-19 cases include bilateral, multilobar ground-glass opacification with a peripheral or posterior distribution (or both), mainly in the lower lobes (17) (18) . According to our study, chest CT showed similar characteristics in the majority of patients, such as ground-glass opacification 335 (51%), bilateral involvement 595 (91%), peripheral distribution 569 (87%), and multilobar (more than two lobes) involvement 573 (87%). Pleural effusion, pericardial effusion, cavitation, pneumothorax, and J o u r n a l P r e -p r o o f lymphadenopathy are some of the uncommon but possible findings seen with disease progression (19-20). In our study, halo sign (20%) and air bronchogram (33%) findings were found to be relatively high on admission.

Istanbul is an overpopulated city that can be seen as a reflection of Turkey by having significant citizen diversity as a result of being a migration receiving city. At the same time, this city has been the center of COVID-19 pandemic. During the Covid-19 pandemic, the majority of cases in our country were placed in this city. Therefore it can be said that it is important in terms of the data reflect the turkey.

This study has several limitations. First of all, it shows the results of a single-center in Istanbul, Turkey. Second, Due to the retrospective nature of the study, the missing data were collected from the patients' electronic medical records. This precluded the level of detail possible with a manual medical record review. Thirdly, some laboratory tests (for example, D-Dimer, IL-6) were not done in all the patients, and missing data or important tests might lead to bias of clinical characteristics.

This case series provides characteristics and outcomes of sequentially adult patients hospitalized with laboratory-confirmed COVID-19 pneumonia in Istanbul, Turkey. In addition, it reveals risk factors associated with mortality.

Funding: There is no source of funding. * P values indicate differences between elderly and non-elderly patients. 

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Abbreviations: NA, not applicable

* P values indicate differences between elderly and non-elderly patients. Lower Upper

Our sincere thanks to all healthcare professionals for their brave efforts in COVID-19 treatment, prevention, and control.

Non-elderly patients (n =487) Elderly patients (n =235)

Leucocytes, ×103/µL (normal range 4. 1 -11) 6.2 (4.9-8.1) 5.9 (4.8-7.7) 6.6 (5. 2