key: cord-0721996-j04nyg5y
authors: Lv, Zhihua; Cheng, Shaohua; Le, Juan; Huang, Jingtao; Feng, Lina; Zhang, Binghong; Li, Yan
title: Clinical characteristics and co-infections of 354 hospitalized patients with COVID-19 in Wuhan, China: a retrospective cohort study
date: 2020-05-18
journal: Microbes Infect
DOI: 10.1016/j.micinf.2020.05.007
sha: 86d6639c0a2abc4f7f48d58c3fdd7b420eb20f28
doc_id: 721996
cord_uid: j04nyg5y

From December 2019, a novel coronavirus, SARS-CoV-2, caused an outbreak of pneumonia in Wuhan city and rapidly spread throughout China and globally. However, the clinical characteristics and co-infection with other respiratory pathogens of patients with COVID-19 and the factors associated with severity of COVID-19 are still limited. In this retrospective cohort study, we included 354 inpatients with COVID-19 admitted to Renmin Hospital of Wuhan University from February 4, 2020 to February 28, 2020. We found levels of interleukin-6, interleukin-10, C-reactive protein, D-dimer, white blood cell count and neutrophil count were clearly elevated in males and critical cases compared with females and severe and mild cases, respectively. However, lymphopenia was more severe in males than females and levels of tumor necrosis factor alpha were reduced significantly in critical cases than severe and mild cases. 23.5% of severe cases and 24.4% of critical cases were co-infected with other respiratory pathogens. Additionally, stepwise multivariable regression analysis suggested that co-infection, lymphocyte count and levels of D-dimer were associated with severity of COVID-19.These findings provide crucial clues for further identification of the mechanisms, characteristics and treatments of patients with COVID-19.

From December 2019, a novel coronavirus, SARS-CoV-2, caused an outbreak of 2 pneumonia in Wuhan city and rapidly spread throughout China and globally. However, the 3 clinical characteristics and co-infection with other respiratory pathogens of patients with 4 COVID-19 and the factors associated with severity of COVID-19 are still limited. In this 5 retrospective cohort study, we included 354 inpatients with COVID-19 admitted to Renmin 6 Hospital of Wuhan University from February 4, 2020 to February 28, 2020. We found levels 7 of interleukin-6, interleukin-10, C-reactive protein, D-dimer, white blood cell count and 8 neutrophil count were clearly elevated in males and critical cases compared with females and 9 severe and mild cases, respectively. However, lymphopenia was more severe in males than 10 females and levels of tumor necrosis factor alpha were reduced significantly in critical cases 11 than severe and mild cases. 23 .5% of severe cases and 24.4% of critical cases were 12 co-infected with other respiratory pathogens. Additionally, stepwise multivariable regression 13 analysis suggested that co-infection, lymphocyte count and levels of D-dimer were associated 14 with severity of COVID-19.These findings provide crucial clues for further identification of 15 the mechanisms, characteristics and treatments of patients with COVID-19. 23 Since December 2019, an outbreak of unexplained pneumonia, now known as 24 coronavirus disease 2019 , occurred in Wuhan city and rapidly spread 25 throughout China and globally [1] [2] [3] [4] [5] . A novel coronavirus named as the 2019-nCoV 26 previously and renamed as SARS-CoV-2 by International Committee on Taxonomy of 27 Viruses [6] was isolated from these patients in Wuhan by Chinese scientists On Jan 10, 2020. 28 Full-genome sequencing and phylogenic analysis suggested that SARS-CoV-2 originated via 29 natural selection [7] differs from Middle East respiratory syndrome-CoV and severe acute 30 respiratory syndrome-CoV [8] [9] [10] . It was found that the SARS-CoV-2 infection could cause 31 not only clusters of severe respiratory illness similar to SARS-CoV-1, but also mild upper 32 respiratory diseases and asymptomatic infection [11] [12] [13] . 33 Although previous studies have demonstrated certain clinical characteristics of patients 34 with COVID-19 [8, 11, 12] , their detail clinical characteristics are still limited and the sex 35 differences in clinical characteristics of COVID-19 patients have not been well studied. 36 Moreover, details of the laboratory assessments such as complete blood count, coagulation 37 profile, serum biochemical tests and inflammatory factors associated with severity of 38 COVID- 19 have not yet been well described. In addition, previous studies have shown that 39 patients with COVID-19 can co-infected with other respiratory virus [14] and will also have 40 secondary infections with bacteria and fungi [13, 15] Data were collected from routine clinical practice, and informed consent was not required. necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) and D-dimer, which is a significant 62 prognostic factor in patients with suspected infection and sepsis [16] . 63 64 Throat-swab specimens from the upper respiratory tract that were obtained from all 65 patients at admission were maintained in viral-transport medium. All patients included were 66 5 verified as positive for SARS-CoV-2 infection in throat swabs analyzed by real-time RT-PCR 67 using the same protocol described previously [11] . respectively. Subsequently the dominant colonies were picked for bacterial and fungus 87 detection using the VITEK MS system (bioMérieux, Marcy l'Etoile, France). 88 6 Routine blood examinations were complete blood count, coagulation profile, serum 89 biochemical tests (including renal and liver function, creatine kinase, lactate dehydrogenase, 90 and electrolytes), myocardial enzymes, interleukin-6 (IL-6), serum ferritin, and procalcitonin. were men and the median age was 62 years (range, 23-90 years) ( Table 1) . Comorbidities 107 were present in nearly one third of patients, with hypertension being the most common 108 comorbidity, followed by diabetes and coronary heart disease (table 1). Based on clinical 109 characteristics the study group was further divided into subjects presenting mild symptoms Table 2 ). The levels of IL-6 123 and IL-10 were increased substantially in patients of severe and critical groups. Differently, 124 the levels of TNF-αwere decreased substantially in patients of severe and critical groups. 125 However, there were no significant differences in levels of PCT among these three groups. 126 

To investigate the differences between genders, we compared some laboratory parameters 128 of 175 males and 179 females. Preliminary analysis indicated that higher white blood cell and 129 neutrophil counts, as well as higher levels of D-dimer, IL-6, IL-10, CRP and PCT were found 130 in male patients compared to those of females, which was similar to patients in critical and 131 severe groups compared with those of mild groups (Table 2) . Differently, lymphocytopenia 132 8 was significantly more severe in males than females (Table 2) . However, there were no 133 significant differences in levels of INF-αbetween genders ( Table 2) . Higher white blood cell and neutrophil counts, as well as higher levels of D-dimer, IL-6, 155 IL-10, CRP and PCT were observed in patients co-infected with other respiratory pathogens 156 than those of infected with SARS-CoV-2 homogeneously (Table 2) . 157 158 Stepwise multivariable regression models were used to find the association of severity of (Table   166 3). 

In this retrospective cohort study, we used 354 samples to make a preliminary assessment 170 of the clinical characteristics of patients with COVID-19 from the following and aspects such 171 as gender, clinical classification and co-infection with other respiratory pathogens. 172 Previous studies suggested that increased age was associated with death in patients with 173 SARS-CoV-1, MERS and COVID-19 [17] [18] [19] . However, no significant differences were 174 found in ages among these three clinical classification groups in this study. Whereas，we 175 found 63.64% (7/11) of the 11 non-survivors were co-infected with other respiratory COVID-19 was more likely to affect men than women, and the symptoms seems to more 189 severe in men [13] . In this study, sex bias in the fatality rate was observed. And lower 190 lymphocyte count, higher white blood cell and neutrophil counts, as well as higher levels of 191 D-dimer, IL-6, IL-10, CRP and PCT were observed in male patients, which was similar to 192 patients in critical and severe groups compared with those of mild groups. However, the 193 mechanisms underlying these differences are still not clear. The reduced susceptibility of 194 females to SARS-CoV-2 infections could be depended on the protection of X chromosome 195 and sex hormones, which played an important role in innate and adaptive immunity [20] . 196 Previous studies have found higher percentages of SARS-CoV-1 infection in male mice than 197 in female mice and provided mechanistic insights related to estrogen [21] . Additionally，17 198 11 β-estradiol could down-regulate lung ACE2 mRNA ， the putative receptor of 199 SARS-CoV-2 [4] ，and protect females from influenza A virus pathogenesis [22] . 200 Previous studies suggested that patients with COVID-19 can also co-infect with other 201 respiratory pathogens such as viruses, bacteria and fungi [13] [14] [15] . In this study, can be detected from SARS-CoV-1 patients [23, 24] , and one case co-infected with 213 SARS-CoV-2 and human metapneumovirus was reported [14] . However, only 1 case was 214 infected with boca virus in 79 patients detected of 13 respiratory pathogens. These issues 215 demonstrate that susceptibility to co-infection with other viruses may be reduced in 216 SARS-CoV-2 patients. Additionally, for the samples were collected and tested 3 to 5 days 217 after patients admitted to hospital, the viruses co-infected with SARS-CoV-2 may be cured. Abbreviations: IL-2, interleukin-2; IL-4, interleukin-4; IL-6,interleukin-6; IL-10, interleukin-10; IFN-γ, Interferon-gamma; TNF-α, Tumor necrosis factor alpha; CRP, C-reactive protein; PCT, procalcitonin. P<0.05 was considered statistically significant.

1 Table 3 Stepwise multivariable regression analysis of factors associated with severity of COVID-19 

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No founding was received. We thank all clinicians and inspectors at the front line of 239 COVID-19 epidemic. 

 235 The authors declare that they have no competing interests.