key: cord-0768317-qlkt5fzp
authors: Wang, Yafei; Zhou, Ying; Yang, Zhen; Xia, Dongping; Geng, Shuang
title: Clinical Characteristics of Patients with Severe Pneumonia Caused by the 2019 Novel Coronavirus in Wuhan, China
date: 2020-03-03
journal: nan
DOI: 10.1101/2020.03.02.20029306
sha: 70cc2e5152d3dc4d44494124ff556c9bbe9e6f41
doc_id: 768317
cord_uid: qlkt5fzp

Abstract Background: A new virus broke out in Wuhan, Hubei, China, and was later named 2019 novel coronavirus (2019-nCoV). The clinical characteristics of severe pneumonia caused by 2019-nCoV are still not clear. Objectives: The aim of this study was to explore the clinical characteristics and risk factors of the severe pneumonia caused by the 2019-nCoV in Wuhan, China. Method: The study included patients hospitalized at the central hospital of Wuhan who had been diagnosed with a pneumonia caused by the novel coronavirus. Clinical features, chronic co-morbidities, demographic data, laboratory examinations, and chest computed tomography (CT) scans were reviewed through electronic medical records. SPSS was used for data analysis to explore the clinical characteristics and risk factors of the patients with the severe pneumonia. Results: A total of 110 patients diagnosed with 2019 novel coronavirus pneumonia were included in the study, including 38 with severe pneumonia and 72 with non-severe pneumonia. Statistical analysis showed that advanced age, an increase of D-dimer, and a decrease of lymphocytes were characteristics of the patients with severe pneumonia. Moreover, in the early stage of the disease, chest CT scans of patients with the severe pneumonia showed the illness can progress rapidly. Conclusions: Advanced age, lymphocyte decline, and D-dimer elevation are important characteristics of patients with severe pneumonia. Clinicians should focus on these characteristics to identify high-risk patients at an early stage.

In December 2019, a new type of unexplained pneumonia was reported in Wuhan, Hubei, China, 21 which appeared to be related to the Huanan Seafood Wholesale Market [1] [2] [3] . The disease spread 22 rapidly from Wuhan to the surrounding provinces and cities, which got the attention of the government 23 and the administrative departments of health at all levels. The Chinese Center for Disease Control and 24 Prevention (CDC) promptly organized the relevant disease control agencies, medical units, and 25 research institutes to carry out investigations and treatment. A new type of coronavirus was detected 26 by researchers in a patient's bronchoalveolar lavage fluid sample on January 3, 2020 [4] . The World 27 Health Organization (WHO) named it the 2019-novel coronavirus (2019-nCoV) and announced that 28 the new coronavirus epidemic had been listed as a public health emergency of international concern on 29 January 30, 2020. As of 18:00 on February 11, 2020, there were 42,744 confirmed cases, 21,675 30 suspected cases, 4,161 cured cases, and 1,017 deaths in China . 31 The 2019-nCoV, which belongs to the genus betacoronavirus, is a single-stranded positive-strand 32 RNA virus that appears to be distinct from, but is related to, other coronaviruses, such as severe acute 33 respiratory syndrome-related coronavirus (SARSr-CoV) and Middle East respiratory syndrome 34 coronavirus (MERSr-CoV) [4] [5] [6] [7] [8] . Current studies have shown that 2019-nCoV has about an 89% 35 homology with bat SARS-like-CoVZXC21 and 82% homology with human SARS-CoV [9] . The 36 disease is highly contagious, and may rapidly develop into severe pneumonia, acute respiratory 37 distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), and death, so the top 38 priority for clinicians is to identify and treat the severest patients in the early stage. The aim of this 39 study was to assess the potential high-risk factors of 2019-nCoV severe pneumonia and provide 40 evidence for the screening of severely afflicted patients. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.02.20029306 doi: medRxiv preprint results. High-resolution CT scans with a scan layer thickness of 5 mm and a reconstruction of a 1-1.5 54 mm thin layer are recommended for the radiological examination of 2019n-CoV pneumonia. Based on 55 the patients' exposure history, clinical symptoms, laboratory examinations, and chest CT scans, all of 56 the patients were clinically diagnosed with 2019-nCoV pneumonia according to WHO's interim 57 guidance [10] . For patients who were suspected to have the illness, two senior respiratory doctors made 58 the diagnosis together. 59 The patients were divided into two groups: patients with severe pneumonia and those with non-severe 60 pneumonia. The former referred to patients with the following severe manifestations: fever or 61 suspected respiratory infection, plus one of a respiratory rate >30 breaths/min, severe respiratory 62 distress, or SpO2 <90% on room air. Patients with ARDS, sepsis, or septic shock were also included. 63 The patients without the above severe signs were defined as having non-severe pneumonia. Patients The patient data were extracted from the Central Hospital of Wuhan, which is a tertiary teaching 69 hospital and is responsible for the treatment for patients with 2019-nCoV pneumonia, as assigned by 70 the Chinese government. Clinical features, chronic co-morbidities, demographic data, laboratory 71 examinations, and chest CT scans were reviewed using electronic medical records. Laboratory 72 examinations included routine blood tests, as well as tests of the liver function, kidney function, 73 electrolytes, B-type natriuretic peptide, D-dimer, C-reactive protein, and procalcitonin. We obtained 74 the lymphocyte absolute values of patients with severe pneumonia on the first day and the third day 75 after admission. The D-dimer data of patients with severe pneumonia on the first day, the third day, 76 and the seventh day after admission were also collected. Chest CT scans were reviewed on the first 77 day and the third day for patients with severe pneumonia. In addition to collecting the albumin data on 78 the first day after admission, the data on the seventh day were also obtained for patients with severe 79 pneumonia. For patients with non-severe pneumonia, we only collected the data on the first day after 80 admission because the relevant items were not frequently reviewed. For patients admitted to the RICU, 81 the Acute Physiology and Chronic Health Evaluation II scores (APACHE-II) and Sequential Organ 82 Failure Assessment (SOFA) were determined on the first day. The data were acquired by physicians. 83 All of the data were checked by another researcher to ascertain its accuracy. To reflect the progression 84 of the disease in critically ill patients, we calculated the difference in the lymphocyte values between 85 day 3 and day 1, the difference in the serum albumin values between day 7 and day 1, and the 86 difference in the D-dimer values between days 3, 7, and 1.

88 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint . https://doi.org/10.1101/2020.03.02.20029306 doi: medRxiv preprint

The continuous variables were used as the mean and compared using the t-tests if they were normally 89 distributed, or they were described using the median. The Mann-Whitney U test was used for 90 comparisons. Categorical variables were expressed as count (%) and compared by χ² test or Fisher's 91 exact test. Logistic regression analysis was used to assess the risk factors of severe pneumonia. The 92 difference of a certain indicator in the same patient at different periods was shown by a bar chart. A 93 two-sided α of less than 0.05 was considered statistically significant. We used SPSS software (version 94 23.0) for statistical analysis.

Basic characteristics 97 A total of 110 hospitalized patients participated in this study, which included 38 (34.5%) patients with 98 severe pneumonia and 72 (65.5%) patients with non-severe pneumonia. incidence of diabetes and cerebrovascular disease was similar in both groups. According to the 106 patients' medical history, the common symptoms at the onset of the illness were fever, fatigue, dry 107 cough, and dyspnea. Although the initial symptoms of the patients with severe pneumonia were more 108 commonly fever and dyspnea, and the difference was not statistically significant. The temperature The laboratory examinations showed that patients with severe pneumonia had depressed serum 148 albumin, elevated serum creatinine, blood urea nitrogen, aspartate aminotransferase, C-reactive protein, 149 and B-type natriuretic peptide. Hypoproteinemia may be due to the patient's consumption and 150 inadequate protein intake caused by poor appetite. A previous study reported that hypoalbuminemia is 151 a potent, dose-dependent predictor of poor outcomes for pneumonia with the coronavirus infection [11] . 152 An elevated amount of C-reactive protein may be associated with the inflammatory response and 153 cytokine storms caused by the virus in the blood vessels. These results were consistent with a previous 154 study, which showed that the C-reactive protein level was positively correlated with the severity of the 155 pneumonia [12] .

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint . https://doi.org/10.1101/2020.03.02.20029306 doi: medRxiv preprint According to the results of the binomial logistics regression analysis, we found that age and the level 157 of the D-dimer were independent risk factors. These results suggested that the level of D-dimer was 158 significantly positively correlated with the 2019-nCoV severe pneumonia, which was also shown in 159 another study [13] . Previous studies showed that SARS-CoV could bind to ACE2, down-regulating the 160 expressions of ACE2, and resulting in an increased Angiotensin II level in mouse blood samples, 161 signaling through Angiotensin II receptor 1, and induced acute lung injury [14] [15] [16] . ACE2 is a receptor 162 protein of both SARS-CoV and 2019-nCoV, and it is abundantly present in the epithelia of the lung 163 and small intestine [17] . It was reported that 2019-nCoV binds to the ACE2 in the same way as SARS- 164 CoV [18] , inducing damage to the pulmonary arteries and leading to the extensive embolization in the 165 extensive alveolar terminal capillaries. These changes eventually lead to an increase in D-dimer. A 166 significant lymphocyte decline in the progression of severe pneumonia was also observed, which was 167 consistent with the results of Huang et al [19] . Decreased lymphocytes suggested that 2019-nCoV may 168 primarily attack the body's immune system, especially the T lymphocytes, which is similar to the 169 action of SARS-CoV [20] . After 2019-nCoV impairs the immune system, it is difficult to prevent the is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this 190 manuscript.

The study was approved by Ethics Committee of Wuhan Central Hospital (Yuan lun han [2020] no.4). 193 As this study was a retrospective study, only clinical data of patients were collected, and privacy data 194 such as name, ID number and telephone number were not involved, so no informed consent was 195 obtained. Moreover, the data were only used for scientific research, not for other purposes. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint . https://doi.org/10.1101/2020.03.02.20029306 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint  The SD of the absolute value of the lymphocytes is 0.55;

 The SD of the D-dimer is 3.25.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.02.20029306 doi: medRxiv preprint CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.02.20029306 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.02.20029306 doi: medRxiv preprint Next Row: Chest CT on Jan 13 showed improved status (3B) with diffuse consolidation of both lungs, uneven density and air bronchogram.

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(which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.02.20029306 doi: medRxiv preprint

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