key: cord-1047134-4egg7q22
authors: Toutkaboni, Mihan Pourabdollah; Askari, Elham; Khalili, Nastaran; Tabarsi, Payam; Jamaati, Hamidreza; Velayati, Ali Akbar; Dorudinia, Atosa; Rezaei, Mitrasadat; Nadji, Seyed Alireza; Mohamadnia, Abdolreza; Khalili, Neda
title: Demographics, laboratory parameters and outcomes of 1061 patients with COVID-19: A report from Tehran, Iran
date: 2020-10-05
journal: New Microbes New Infect
DOI: 10.1016/j.nmni.2020.100777
sha: 0a1a319ffd87d5b69e7738e57c382a3fc3c8b420
doc_id: 1047134
cord_uid: 4egg7q22

We aimed to determine the characteristics of coronavirus disease-2019 among the Iranian population. In this study, we collected and analyzed the demographics, laboratory findings and outcomes of patients with COVID-19 who were admitted to Masih Daneshvari Hospital in Tehran, Iran between February 20, 2020 and April 2, 2020. Of 1061 patients, the median age was 55 years (interquartile range [IQR], 44-66 years) and 692 (65.2%) were male. Among these, 129 (12.2%) patients died at some point during hospitalization in the ward or intensive care unit (ICU). From the remaining 932 survivors, 46 (5.0%) patients were admitted to the ICU and 886 (95.0%) patients were hospitalized in the ward. Patients who died were significantly older than those hospitalized in the ward (p<0.001). The median absolute number of lymphocytes was 1.2 × 103 per microliter (IQR, 0.9-1.6 × 103 per microliter) and 708 (66.7%) patients had lymphopenia (absolute lymphocyte count <1500 per microliter). Among the laboratory tests, D-dimer, serum ferritin and albumin had the strongest correlation with mortality (r = 0.455, r = 0.412, r = -0.406, respectively; p-values <0.001). Conclusively, laboratory findings could provide useful information in regard to the management of patients with COVID-19.

In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 23 identified in Wuhan City, Hubei province, China (1). The disease caused by this highly 24 contagious viral pathogen, which was later named as the novel coronavirus disease 2019 25 (COVID-19) by the World Health Organization (WHO), spread rapidly to other countries, 26 including Iran, South Korea, and Italy. As of May 13, 2020, 188 countries have reported 27 confirmed cases of COVID-19 with more than 293,241 deaths having occurred worldwide (2).

Patients infected with this novel betacoronavirus mostly manifest with fever, cough, dyspnea, 29 headache and fatigue (3, 4) . In a minority of patients, SARS-CoV-2-associated pneumonia can 30 lead to severe complications such as, acute respiratory distress syndrome, multiple organ failure 31 and even death (3-6).

According to literature, patients with COVID-19 are prone to developing lymphopenia, increased 33 neutrophil count and thrombocytopenia (4, 7, 8) . More recently, neutrophil-to-lymphocyte ratio 34 (NLR) and platelet-to-lymphocyte ratio (PLR) were proposed as potential predictors of mortality 35 in confirmed cases of . Higher levels of infection-related markers, including C-36 reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer, serum ferritin, and 37 proinflammatory cytokines (IL-6, IL1B, IFNγ, TNFα) have also been suggested as markers of 38 disease progression in several studies (12) (13) (14) . 39 The vast majority of studies describing the demographics and clinical characteristics, as well as computed tomography (CT) findings, were included in this study. Demographic data including 54 age, sex, date of admission, and laboratory findings were collected from patients' electronic 55 medical records. One researcher reviewed the data collection forms for quality control. No age 56 limitation was considered in our study; however, approximately all included patients were adults.

Final follow-up date was May 1, 2020. Patients were divided into three main groups: patients 58 who were admitted to the ward, patients who were admitted to the intensive care unit (ICU) and 59 those who died until follow-up. It should be noted that patients who had died by the end of final 60 follow-up but had also received care in the ICU/ward during hospitalization were included in the 61 'expired' group, and all the patients in the 'ward' and 'ICU' groups had survived until final 62 follow-up date. This study was approved by the ethics committee of Shahid Beheshti University respectively. The Kolmogorov-Smirnov test was conducted to assess the distribution normality.

To compare the continuous variables between the groups, one-way ANOVA and Kruskal Wallis 84 tests were used for parametric and non-parametric data, respectively. Chi-square test was used 85 for comparing categorical data between groups. Subgroup analysis was also performed for 86 patients who had a positive RT-PCR test. Pearson's correlation test was used for assessing the 87 J o u r n a l P r e -p r o o f correlation between mortality and variables. Patients were divided into two categories for this 88 analysis; those who were admitted to the ICU or ward were grouped as survivors and those 89 patients who died during the study period formed the non-survivors group. All statistical 90 analyses were performed with SPSS software version 23.0 (IBM corp., Chicago, IL, USA). P-91 values less than 0.05 were considered as statistically significant. Three age groups were defined: 92 patients less than 21 years old, patients aged 21-64 years, and those older than or equal to 65 93 years.

Total study population 96 A total of 1061 hospitalized patients were included in this study. Among these, 129 (12.2%) 97 patients died at some point during hospitalization in the ward or intensive care unit (ICU). From 98 the remaining 932 survivors, 46 (5.0%) patients were admitted to the ICU and 886 (95.0%) 99 patients were hospitalized in the ward. The median age of all patients was 55 (44-66) years, and 100 65.2% of the cases were males. Also, the median age of those who died was 65 years and no 101 significant difference in age was seen between patients who died and those who received ICU 102 care (p=0.064); however, patients who died were significantly older than those hospitalized in 103 the ward (p<0.001). Although all patients were considered as COVID-19 positive cases, only 104 53.6% had a positive RT-PCR test. The laboratory findings of patients within each group are 105 demonstrated in Table 1 . As shown, 126 (12.3%) patients had leukopenia and 708 (66.7%) had 106 lymphopenia at baseline. The median absolute number of lymphocytes was 1.2 × 10 3 per 107 microliter (IQR, 0.9-1.6 × 10 3 per microliter). Among laboratory tests, only hemoglobin level, performing a subgroup analysis, we found that results were similar to that of the total population 131 except for ALT and serum ferritin, which did not vary significantly between the three groups 132 J o u r n a l P r e -p r o o f (p=0.307 and p=0.135, respectively), and PTT, which was found to be statistically different 133 across groups (p=0.047) ( Table 2) .

Correlation between mortality and study variables 135 As shown in Table 3 (Table 3) . follow-up date but had received ICU care prior to death were not included in the 'ICU' group.

Many studies have investigated laboratory findings in COVID-19 that are associated with disease 168 severity. Generally, patients with COVID-19 tend to have abnormal blood counts, coagulopathy, 169 and liver and kidney dysfunction (4, 8). Higher serum CRP, D-dimer, LDH, creatine kinase and 170 procalcitonin levels have been found among patients with severe disease (17, 18, 23, 24) . In this 171 study, D-dimer, serum ferritin and albumin had the strongest correlation with mortality.

Although albumin has a half-life of 15 to 19 days, it is more rapidly decreased than expected 173 during the course of COVID-19 infection. Elevated levels of inflammatory cytokines, 174 particularly IL-6, increase vascular permeability during an acute-phase response and result in the 175 redistribution of albumin into the interstitial space (25). In addition, increased IL-6 may induce 176 apoptosis in lymphocytes, leading to lymphopenia in patients with . Of note, our 177 J o u r n a l P r e -p r o o f study failed to show a significant difference in IL-6 levels between the three groups; however, in 178 contrast to patients admitted to the ward or ICU, the median IL-6 level (10.1 pg/ml) was higher 179 than the upper limit of normal (5.9 pg/ml) in patients who died. Another finding of this study 180 was that patients who died had significantly increased ESR and serum ferritin levels and a higher 181 proportion of positive CRP compared with those admitted to the ward. These results suggest that 182 patients with severe disease have an increased activity of the innate immune system. As 

Among all patients, approximately 67% had lymphopenia; this is in accordance with previous 203 reports that have indicated a diagnostic value for lymphopenia in patients with COVID-19 on 204 admission (12, 17, 28, 33, 34) . According to our results, patients who died were more likely to 205 have WBC count of more than 10.0 × 10 3 per microliter compared with patients who received 206 care in the ward. In a single-center study by Qu and colleagues, a higher PLR was proposed as a 207 prognostic indicator of prolonged hospitalization in confirmed cases of COVID-19. They also 208 found that patients with a peak in the absolute count of platelets during the disease course had 209 poor outcomes (11). Likewise, in our study, PLR values were markedly lower in the ward 210 patients compared with those who died. Interestingly, only lymphocyte percentages were 211 significantly lower in patients admitted to the ICU compared with those hospitalized in the ward. In this study, we included 1061 patients who were treated as COVID-19 patients; however, 223 nearly half of these patients had a positive RT-PCR test while the remaining patients tested 224 negative. Since the current gold standard test for the diagnosis of COVID-19 is RT-PCR, we 225 performed a subgroup analysis among patients with laboratory-confirmed Notwithstanding, the results were relatively similar to those of the total population.

Our study has several limitations. First, we did not report the detailed clinical and radiologic 228 manifestations of the included population due to lack of access to data. Thus, we were not able to 229 evaluate the severity of disease based on predefined classifications by international agencies.

Second, we did not consider the comorbidities of patients, a factor that may have an important 231 role in the mortality of patients with COVID-19 (6). In addition, due to the retrospective nature 232 of the study, we did not have access to complete lab data for all patients, which might potentially 233 reduce the strength of the reported findings.

In conclusion, the results of this study suggest that laboratory abnormalities are seen in patients 

A Novel Coronavirus from Patients with 245 Pneumonia in China

Clinical characteristics of 138 hospitalized 247 patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China

Clinical features of patients infected with 2019 249 novel coronavirus in Wuhan, China. The lancet

Clinical Characteristics of Coronavirus 251 Disease 2019 in China

Epidemiological and clinical characteristics 253 of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Novel Coronavirus-Infected Pneumonia in Wuhan, China

Thrombocytopenia is associated with severe coronavirus disease 259 2019 (COVID-19) infections: A meta-analysis

Hematologic parameters in 261 patients with COVID-19 infection. American journal of hematology

The diagnostic and predictive role of NLR, d-NLR and PLR in 263 COVID-19 patients

Neutrophil-to-lymphocyte ratio as an 265 independent risk factor for mortality in hospitalized patients with COVID-19

Platelet-to-lymphocyte ratio is associated with 267 prognosis in patients with Corona Virus Disease-19

Clinical and immunological features of 269 severe and moderate coronavirus disease 2019

Early clinical and CT manifestations of 271 coronavirus disease 2019 (COVID-19) pneumonia

Clinical Course and Outcomes of 273 Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary

First 28 Patients from the Korean Cohort Study on COVID-19

Clinical course and risk factors for mortality of adult 276 inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The lancet

Lobar Distribution of 278 COVID-19 Pneumonia Based on Chest Computed Tomography Findings; A Retrospective Study. Arch 279

Clinical characteristics of 140 281 patients infected with SARS-CoV-2 in Wuhan

Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. 284 JAMA Internal Medicine

Analysis of the Clinical Characteristics of 77 COVID-286 19 Deaths

The clinical characteristics and mortal 288 causes analysis of COVID-19 death patients

ICU, intensive care unit; NLR, 339 neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio, ESR, erythrocyte 340 sedimentation rate; CRP, C-reactive protein; WBC, white blood cell; Hgb, hemoglobin; PLT, 341 platelet; PCR, polymerase chain reaction; LDH, lactate dehydrogenase; AST, aspartate 342 aminotransferase; ALT, alanine aminotransferase

Validation Elham Askari: Resources, Writing -Review & Editing, Supervision

Visualization, Supervision, Validation Atosa Dorudinia: Resources, Visualization, Investigation Mitrasadat Rezaei: Resources, Visualization, Investigation Seyed Alireza Nadji: Resources, Visualization Abdolreza Mohamadnia: Resources, Visualization Neda Khalili: Writing -Original Draft