key: cord-0906395-jka8qdgg
authors: Feng, X.; Li, P.; Ma, L.; Liang, H.; Lei, J.; Li, W.; Wang, K.; Song, Y.; Li, S.; Yang, W.; Yang, C.
title: Clinical Characteristics and Short-Term Outcomes of Severe Patients with COVID-19 in Wuhan, China
date: 2020-04-29
journal: nan
DOI: 10.1101/2020.04.24.20078063
sha: fda9e88a710b43076bcf7e1e4cd67f64887d15a6
doc_id: 906395
cord_uid: jka8qdgg

Objective. A novel pneumonia (COVID-19) which is sweeping the globe was started in December, 2019, in Wuhan, China. Most deaths occurred in severe and critically cases, but information on prognostic risk factors for severe ill patients is incomplete. Further research is urgently needed to guide clinicians, so we prospectively evaluate the clinical outcomes of 114 severe ill patients with COVID-19 for short-term in the Union Hospital in Wuhan, China. Methods. In this single-centered, prospective and observational study, we enrolled 114 severe ill patients with confirmed COVID-19 from Jan 23, 2020 to February 22, 2020. Epidemiological, demographic and laboratory information were collected at baseline, data on treatment and outcome were collected until the day of death or discharge or for the first 28 days after severe ill diagnosis, whichever was shorter. Univariate and multivariate Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) of poor outcome. Results. Among enrolled 114 patients, 94 (82.5%) had good outcome while 20 (17.5%) had poor outcome. No significant differences were showed in age, gender and the prevalence of coexisting disorders between outcome groups. Results of multivariate Cox analyses indicated that higher levels of oxygen saturation (HR, 0.123; 95% CI, 0.041-0.369), albumin (HR, 0.060; 95% CI, 0.008-0.460) and arterial partial pressure of oxygen (HR, 0.321; 95% CI, 0.106-0.973) were associated with decreased risk of developing poor outcome within 28 days. In the other hand, higher levels of leucocytes (HR, 5.575; 95% CI, 2.080-14.943), neutrophils (HR, 2.566; 95% CI, 1.022-6.443), total bilirubin (HR, 6.171; 95% CI, 2.458-15.496), globulin (HR, 2.526; 95% CI, 1.027-6.211), blood urea nitrogen (HR, 5.640; 95% CI, 2.193-14.509), creatine kinase-MB (HR, 3.032; 95% CI, 1.203-7.644), lactate dehydrogenase (HR, 4.607; 95% CI, 1.057-20.090), hypersensitive cardiac troponin I (HR, 5.023; 95% CI, 1.921-13.136), lactate concentration (HR,15.721; 95% CI, 2.099-117.777), Interleukin-10 (HR, 3.551; 95% CI, 1.280-9.857) and C-reactive protein (HR, 5.275; 95% CI, 1.517-18.344) were associated with increased risk of poor outcome development. We also found that traditional Chinese medicine can significantly improve the patient's condition, which is conducive to the transformation from severe to mild. Conclusion. In summary, we firstly reported this single-centered, prospective and observational study for short-term outcome in severe patients with COVID-19. We found that cytokine storm and uncontrolled inflammation responses, liver, kidney, cardiac dysfunction may play important roles in final outcome of severe ill patients with COVID-19. Our study will provide clinicians to be benefit to rapidly estimate the likelihood risk of short-term poor outcome for severe patients.

An outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), centered in Wuhan, Hubei province, in December 2019. [1] It has rapidly spread to other cities and countries outside Wuhan and has become a global health crisis. As the disease progresses, more and more characteristics about the disease are known to us. Up to now, there are still no specific drugs, mainly supporting treatment in clinic. A large number of studies have shown that the main symptom of this disease was fever, cough and dyspnea. [2] [3] [4] [5] Some articles have described the disease in details. Huang gastrointestinal symptoms and proposed that non-classical symptoms have been overlooked, posing a threat to the public. [6] Wu et al discussed that older people (≥65 years old) with greater risk of development of acute respiratory distress syndrome (ARDS) and death. [7] Guo et al found that diabetes is a risk factor for the patients with COVID-19. [8] However, few studies took prospective study to explore the short-term outcomes of severe ill patients under current medical treatment and the risk factors that affect the short-term outcomes of severe ill patients, especially pneumonia patients with certain chronic diseases, which accounted for the majority of deaths. Here, we used a single-centered, prospective method to describe the basic clinical characteristics and short-term outcomes of severe patients in Union hospital, Wuhan, were collected until the day of death or discharge or for the first 28 days after severe ill diagnosis, whichever was shorter. All missing or vague data, direct communications with patients and their families. All data were finally checked by two physicians (Xiaobo Feng and Liang Ma) and a third researcher (Wei Yang) adjudicated any difference in interpretation between the two primary reviewers.

Clinical outcomes of 28 days' consecutive observations of severe patients were divided into two categories, including good outcome (discharge, non-severe or ventilator free) and poor outcome (mechanically ventilated or dead). The criteria of discharge including the temperature returned to normal for more than 3 days (T < 37.3℃), respiratory symptoms were improved significantly, pulmonary imaging showed significant improvement in acute exudative lesions and nucleic acid test was negative for respiratory tract specimens such as sputum and nasopharyngeal swab for two consecutive times (at least 24 hours after sampling). Non-severe mean mild type which is defined as having slight clinical symptoms without pneumonia on radiography. 

Regarding to 114 severe patients, many laboratory indicators differed significantly between outcome groups ( (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Ground-glass opacity. These data indicated that the uncontrolled inflammation responses, infection, liver and kidney dysfunction and hypoxia may contribute to a poor outcome of COVID-19.

The severe patients with COVID-19 had complications of acute liver injury, ARDS, acute kidney injury, arrhythmia, acute myocardial injury, DIC, rhabdomyolysis, septic shock and among them, nobody had septic shock in good outcome group. Otherwise, in poor outcome group, all patients had ARDS. Acute myocardial injury, acute kidney injury, arrhythmia, rhabdomyolysis, DIC were significantly higher than their counterparts of 13.8 %, 22 Interleukin-10 (HR, 3.551; 95% CI, 1.280-9.857) and C-reactive protein (HR, 5.275; 95% CI, All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 29, 2020. Furthermore, we found that there was a nonlinear dose-response relationship between ten indices and poor outcome risk, which is depicted in Figure 2 .

SARS-CoV-2 has now spread globally and seriously threaten the human health.

Demographics and Characteristics of COVID-19 has been gradually investigated and explored by many scientists. Studies had shown that 20% of COVID-19 patients developed to critically disease due to hypoxia or respiratory failure, among them, 5% needed to treat in intensive care unit and 15% required oxygen and essential care. This suggests that this is particularly important in understanding this part of the patient. [9] [10] Recently, Dong et al found that children, in particular, infants developed into severe outcomes. This indicated that patients of any age could develop to severe illness. [11] Feng et al found that severe and critical patients with the typical characteristics of multiple organ and immune function dysfunction. They also found that older people with age ( ≥ 75 years) was a risk factor for mortality.

[12] With the increase number of asymptomatic infectious patients, take measures to detect and isolate early are especially important. In our study, we take a short-term method to prospectively study the reported the epidemiology and risk factors of 114 severe patients with COVID-19 from Union hospital, Hubei province. To our knowledge, this is the first report to describes the severe patients with COVID-19 during a short-term observation and predicted some risk factors for final outcome. In our study, the average age of severe patients All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 29, 2020. . https://doi.org/10.1101/2020.04.24.20078063 doi: medRxiv preprint were 63.96 ± 13.41 years and 58 (50.9%) were older than 65 years, the patients are older than in other studies. [5, 13, 14] We also found that 78 (68.4%) of 114 patients were had fever at initial, this was in accordance with previous studies, which fever is the one of the most common symptom in patients who had COVID-19. [5, [14] [15] [16] argue that this is potential correlation with COVID-19 severity. [20] In addition, markedly higher concentrations of cardiac troponin I, creatine kinase, lactate dehydrogenase could be observed in poor outcome group than in their counterpart. Most notably, patients who had poor outcome may develop pulmonary and extra-pulmonary organ damage, including septic shock, acute respiratory distress syndrome, acute kidney injury, acute cardiac injury as well All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 29, 2020. . https://doi.org/10.1101/2020.04. 24.20078063 doi: medRxiv preprint as disseminated intravascular coagulation. Fatality risk of COVID-19 patients with or without history of previous cardiovascular disease may the acute cardiac injury and heart failure. [18] Costanza Emanueli et al suggested that the COVID-19 crisis will have a longer term residual repercussions on the cardiovascular system. [21] This suggestion that the cardiac injury also requires special attention. In our study, we also found that lactate concentration was higher in poor outcome than their counterpart. As with all known, lactate is generally the end product of energy through anaerobic metabolism, and the elevation of lactate level is mainly caused by the increase of blood oxygen deficiency and anaerobic metabolism, this result is consistent with the lower oxygen saturation in poor group, this indicated that lactate level was an important predictors of poor outcome in the early stage. In addition, total bilirubin was also an important predictor of poor outcome in the early stage. Qi recommend that dynamic monitor the liver function of patients is necessary. [22] Cai conclude that patients with abnormal liver function may had higher risks to progress to severe disease. [23] Due to the "cytokine storm" also observed in poor outcome group, 19 (95.0%) of these patients were (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 29, 2020. All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Values are n (%) for categorical data, means ± SDs for normally distributed data, or medians (IQRs) for non-normally distributed data. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Values are n (%) for categorical data, means ± SDs for normally distributed data, or medians (IQRs) for non-normally distributed data. Data are n (%), means ± SDs or medians (IQRs) when appropriate. Data are n (%) or medians (IQRs) when appropriate. * Data available for 98 patients.

All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 29, 2020 

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