key: cord-0723185-eu3rry7p authors: Lu, Jiatao; Hu, Shufang; Fan, Rong; Liu, Zhihong; Yin, Xueru; Wang, Qiongya; Lv, Qingquan; Cai, Zhifang; Li, Haijun; Hu, Yuhai; Han, Ying; Hu, Hongping; Gao, Wenyong; Feng, Shibo; Liu, Qiongfang; Li, Hui; Sun, Jian; Peng, Jie; Yi, Xuefeng; Zhou, Zixiao; Guo, Yabing; Hou, Jinlin title: ACP risk grade: a simple mortality index for patients with confirmed or suspected severe acute respiratory syndrome coronavirus 2 disease (COVID-19) during the early stage of outbreak in Wuhan, China date: 2020-02-23 journal: nan DOI: 10.1101/2020.02.20.20025510 sha: f854d7b750541d65c48df953a65028a50ce57881 doc_id: 723185 cord_uid: eu3rry7p Background: Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) outbreaks in Wuhan, China, healthcare systems capacities in highly endemic areas have been overwhelmed. Approaches to efficient management are urgently needed and key to a quicker control of the outbreaks and casualties. We aimed to characterize the clinical features of hospitalized patients with confirmed or suspected COVID-19, and develop a mortality risk index for COVID-19 patients. Methods: In this retrospective one-centre cohort study, we included all the confirmed or suspected COVID-19 patients hospitalized in a COVID-19-designated hospital from January 21 to February 5, 2020. Demographic, clinical, laboratory, radiological and clinical outcome data were collected from the hospital information system, nursing records and laboratory reports. Results: Of 577 patients with at least one post-admission evaluation, the median age was 55 years (interquartile range [IQR], 39 - 66); 254 (44.0%) were men; 22.8% (100/438) were severe pneumonia on admission, and 37.7% (75/199) patients were SARS-CoV-2 positive. The clinical, laboratory and radiological data were comparable between positive and negative SARS-CoV-2 patients. During a median follow-up of 8.4 days (IQR, 5.8 - 12.0), 39 patients died with a 12-day cumulative mortality of 8.7% (95% CI, 5.9% to 11.5%). A simple mortality risk index (called ACP index), composed of Age and C-reactive Protein, was developed. By applying the ACP index, patients were categorized into three grades. The 12-day cumulative mortality in grade three (age ≥ 60 years and CRP ≥ 34 mg/L) was 33.2% (95% CI, 19.8% to 44.3%), which was significantly higher than those of grade two (age ≥ 60 years and CRP < 34 mg/L; age < 60 years and CRP ≥ 34 mg/L; 5.6% [95% CI, 0 to 11.3%]) and grade one (age < 60 years and CRP < 34 mg/L, 0%) (P <0.001), respectively. Conclusion: The ACP index can predict COVID-19 related short-term mortality, which may be a useful and convenient tool for quickly establishing a COVID-19 hierarchical management system that can greatly reduce the medical burden and therefore mortality in highly endemic areas. Background: Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) outbreaks in Wuhan, China, healthcare systems capacities in highly endemic areas have been overwhelmed. Approaches to efficient management are urgently needed and key to a quicker control of the outbreaks and casualties. We aimed to characterize the clinical features of hospitalized patients with confirmed or suspected COVID-19, and develop a mortality risk index for COVID-19 patients. In this retrospective one-centre cohort study, we included all the confirmed or suspected COVID-19 patients hospitalized in a COVID-19-designated hospital from January 21 to February 5, 2020. Demographic, clinical, laboratory, radiological and clinical outcome data were collected from the hospital information system, nursing records and laboratory reports. Results: Of 577 patients with at least one post-admission evaluation, the median age was 55 years (interquartile range [IQR] , 39 -66); 254 (44.0%) were men; 22.8% (100/438) were severe pneumonia on admission, and 37.7% (75/199) patients were SARS-CoV-2 positive. The clinical, laboratory and radiological data were comparable between positive and negative SARS-CoV-2 patients. During a median follow-up of 8.4 days (IQR, 5.8 -12.0), 39 patients died with a 12-day cumulative mortality of 8.7% (95% CI, 5.9% to 11.5%). A simple mortality risk index (called ACP index), composed of Age and C-reactive Protein, was developed. By applying the ACP index, patients were categorized into three grades. The 12-day cumulative mortality in grade three (age ≥ 60 years and CRP ≥ 34 mg/L) was 33.2% (95% CI, 19.8% to 44.3%), which was significantly higher than those of grade two (age ≥ 60 years and CRP < 34 mg/L; age < 60 years and CRP ≥ 34 mg/L; 5.6% [95% CI, 0 to 11.3%]) and grade one (age < 60 years and CRP < 34 mg/L, 0%) (P <0.001), respectively. . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.20.20025510 doi: medRxiv preprint After the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease was reported in Wuhan, China in December 2019, an increasing number of confirmed cases were identified over time worldwide. [1] [2] [3] [4] [5] As of February 19, 2020, 74 576 confirmed cases with 2118 deaths were reported in China. 6 Based on the reported clinical characteristics of patients infected with SARS-CoV-2, the overall mortality ranges from 2% to 5%, which can be even higher in the elders with severe complications. 1, 7, 8 The Chinese government responded immediately and mobilized the whole country's health resources to deal with this public health emergency. However, according to the data released at February 19, 2020, the number of confirmed cases in the city of Wuhan accounts for nearly two-thirds of the entire country while the number of deaths accounts for three-quarters of the whole country, and the mortality reached a peak of over 7% at the early stage. Wuhan city, as the epidemic area, is bearing enormous public health as well as medical burdens, and the epidemic condition of the city will robustly impact on the trends of COVID-19 epidemics nation-wide as well as worldwide. Thus, an efficient and timely triage of COVID-19 patients with high mortality risk is crucial for relieving the public health burden. Highly notably, the current confirmation of SARS-CoV-2 infection is entirely based on the viral real-time reverse transcription polymerase chain reaction (RT-PCR) test result. At the 17th COVID-19 Prevention and Control Work Conference by the Hubei Government, it is reported that the overall positive rate of SARS-CoV-2 assay was only 30 -40% in Wuhan among all the detected specimens from highly clinical suspected patients. This low detection rate, presumably due to a high rate of false negativity, of the current assay might lead to delay in diagnosing new COVID-19 patients as well as early discharge of infected patients who still carry the virus and thus remain as the potential infection . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.20.20025510 doi: medRxiv preprint 6 source. Given the current epidemiologic circumstance and the limited health system capacity, optimizing clinical management approach on COVID-19 patients is both critical and urgent. Our current study was conducted aiming to characterize the clinical features of either confirmed or suspected COVID-19 patients who were hospitalized in a COVID-19-designated hospital in Wuhan, and to develop a mortality risk index, as an evaluation tool used for establishing a COVID-19 hierarchical management system in highly endemic areas. We performed a retrospective, one-centre study on patients hospitalized from January 21 to February 5, 2020, at Wuhan Hankou Hospital in Wuhan, China. Wuhan Hankou Hospital was one of the first designated by the Wuhan government to be responsible for admitting patients with confirmed or suspected COVID-19 from Wuhan in January 21, 2020. The hospital was staffed with a team of physicians from Nanfang Hospital, Southern Medical University, starting from January 24, 2020. All patients enrolled in this study were residences in Wuhan and treated according to the Chinese Guidance for COVID-19. 9 All data were provided by Hankou Hospital. The data collected include demographic characteristics, comorbidities, clinical signs, and symptoms, laboratory testing results, chest computed tomography (CT) scan images and clinical outcomes from the hospital information system, nursing records, and laboratory reports. . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.20.20025510 doi: medRxiv preprint Laboratory-confirmed case was defined as the presence of SARS-CoV-2 in respiratory specimens (including nasal and pharyngeal swabs) detected by RT-PCR. Suspected case was defined as meeting two of the following criteria: 1) fever, and/or respiratory symptoms; 2) presence of radiographic pneumonia; 3) white blood cell (WBC) counts within upper limit of normal (ULN) or hypo-lymphocytosis at early course of the disease. According to the Chinese COVID-19 prevention and control program (6th edition), severe disease was defined as meeting one of the following criteria: Specimens from the upper respiratory tracts were collected from suspected patients with COVID-19 to extract SARS-CoV-2. After collection, the specimens were maintained in viral-transport medium and . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.20.20025510 doi: medRxiv preprint Data were expressed as counts and percentages for categorical variables and as median (interquartile range [IQR]) for continuous variables. Qualitative and quantitative differences between subgroups were analysed using chi-square or Fisher's exact tests for categorical parameters and the student t or Mann-Whitney's tests for continuous parameters, as appropriate. The cumulative mortality was calculated using the Kaplan-Meier method, with the log-rank test used for comparisons. Cox The study was conducted in accordance with the guidelines of the Declaration of Helsinki and the principles of good clinical practice, and was approved by the Nanfang Hospital Ethics Committee (NFEC-2020-026). Written informed consent was waived in light of the urgent need to collect clinical data. A total of 577 patients with at least one post-admission evaluation were included in the final analysis. Of these studied patients, the median age was 55 years (IQR, 39 -66) and 254 (44.0%) were men. CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.20.20025510 doi: medRxiv preprint rhinorrhea, and chest pain were less than 5%. The days from illness onset to admission were six days (IQR, 4 -9). At admission, the most common abnormal laboratory test results were elevated C-reactive Among 438 patients with evaluable disease severity, 338 and 100 patients were diagnosed as mild and severe pneumonia, respectively. The cumulative mortality was significantly higher among patients with severe pneumonia than those with mild pneumonia (37.8% vs. 4.1%, P <0.001) (Figure 1 ). On admission, the patients with severe pneumonia, in comparison with the patients with mild pneumonia, CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . 1 0 (20.8% vs. 13.7%, P =0.20); however, the difference is not statistically significant. The SARS-CoV-2 test result does not seem to be related to the clinical characteristics, signs, and symptoms, as well as other laboratory test results and CT scan, except for age and chest pain (Table 1 ). Supplementary figure 1 showed the CT scan images of three pneumonia patients with positive (2) and negative (2) SARS-CoV-2 test results. As was significantly higher than those of grade two (5.6% [95% CI: 0% -11.3%]) and grade one (0%) (P . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . <0.001), respectively ( Figure 2) . Among 12 death patients with In this study, we comprehensively described the clinical characteristics of all the patients with either confirmed or suspected COVID-19 who were hospitalized in a COVID-19 designated hospital during a period from January 21 to February 5, 2020, and then developed a simple prognostic tool called ACP index, only composed of patient's age and CRP tested at admission, that could accurately predict the COVID-19-related mortality risk within 12 days after admission. To our knowledge, this is the first-ever study to compare the clinical characteristics of pneumonia patients who were either positive or negative for SARS-CoV-2 by RT-PCR assay, and to develop a first-ever COVID-19 mortality risk index derived from patients in highly endemic areas during early stage of outbreak. In this large-sample size cohort, the percentage of pneumonia patients with positive results for SARS-CoV-2 result was around 40%, which was consistent with the report of Wuhan government. We found that almost all the characteristics including clinical presentations, laboratory testing results, as . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. With the increasing number of confirmed cases and deaths from SARS-CoV-2 infection, the city of Wuhan is facing a big challenge with the overwhelmed medical capacity to provide essential medical . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The ACP index was consisted of two components -patient's age and CRP tested at admission. Presumably, age should be more likely to correlate with underlying medical conditions and comorbidities. In our cohort, an age of more than 60 years old indicates higher mortality in COVID-19 patients, which is consistent with previous studies on severe acute respiratory syndrome and Middle East respiratory syndrome (MERS) related pneumonia. 11, 12 Moreover, CRP, an indicator of inflammatory response, has been described as a predictor of disease progression in MERS, 13 influenza-infected 14 and community acquire pneumonia patients. 15 In the current study, a CRP levels higher than 34 mg/L in the early course of COVID-19 is associated with increased mortality from SARS-CoV-2 infection, which may reflect an intense inflammatory response or/and an underlying secondary infection. Management decision for high risk patients with COVID-19 must be made quickly, which often based upon scanty evidence. Under this pressing circumstance, the quality of evidence becomes especially crucial. The ACP index, with a high level of differentiating power, can be regarded as such quality evidence in providing an efficient, feasible and accessible approach to establish a hierarchical management system of COVID-19 in the SARS-CoV-2 highly endemic areas where medical resources are extremely limited. To be specific, it is suggested, by applying the ACP index, that patients classified in the grade one (low-risk) group, accounting for about 44.7% of the studied population, should be . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . 1 4 isolated and treated in "Mobile Cabin Hospitals", an isolation place converted from sports stadium, convention centers, etc. with easily installed structures by the government. For patients in the grade two (medium-risk) group, which has the 12-day mortality of approximately 6%, they should be treated in the general wards, whereas the patients in the grade three group should be transferred to intensive care unit for more comprehensive treatment due to as high as 33% mortality within 12 days from admission ( Figure 3 ). It is projected that this approach would benefit a considerable number of patients with COVID-19 by directing the medical resources appropriate for the severity of the disease, and thus reduce the mortality and save the socioeconomic resources. We also comprehensively describe the characteristics of severe (vs. mild) and death patients in our cohort. We noticed that severe patients had high frequencies of decreased lymphocytes, higher D-dimer, and lower albumin, suggesting that severe patients may had higher probability of immune deficiency, coagulation activation, and disease exhaustion condition. In addition, we also noticed abnormal ALT and creatinine levels in most patients who died, but most of the abnormalities were mild, suggesting that COVID-19 patients may die primarily from respiratory failure caused by SARS-CoV-2 infection, rather than multiple organ failure. The high mortality rates in our study may be due to differences in the population composition. Patients in three first designated hospitals are reasonable to have much progressed disease and higher mortality than the national-wide population, as reported by Huang et al and Chen et al. 1, 8 Notably, Hankou Hospital is the nearest medical center from the Huanan wholesale seafood market, which is reported as the first place of cluster onset. Most patients in Hankou Hospital are residents nearby and are believed to be the earliest infected population who may have close contact with live animals or the first generation of confirmed cases. In addition, Wuhan, as the endemic area, includes a considerable . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . proportion of the elders, while those cases outside of Wuhan are mostly young people who work or study in Wuhan but return home during the Spring Festival in January 2020. These age composition differences also contribute to the prognosis quite significantly. On the other hand, suboptimal functioning of the medical care system was highly overwhelmed as too many infected subjects were presented in a very short period. Meanwhile, many patients with mild illness were home isolated in January, which lead to the reality that the current reported mortality level more precisely reflects the death risk of the severe cases. Despite the significant findings in this report, the current study has several limitations. Firstly, some cases had incomplete documentation of the symptoms and laboratory testing given the extremely heavy work of the medical staff. Secondly, the ACP index has not been externally validated yet in an independent prospective cohort. To this end, a new prospective study is under the way to further investigate its value in triaging the COVID-19 patients. Thirdly, the patients enrolled in this study were from a tertiary-care hospital and were more likely to have underlying comorbidities and severe diseases. It is estimated that more patients would belong to the grade one category in the primary care setting. In conclusion, the ACP index can predict COVID-19 related short-term mortality, which may be a useful and convenient tool for quickly establishing a COVID-19 hierarchical management system that can greatly reduce the medical burden and therefore mortality in highly endemic areas. . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . CC-BY-NC-ND 4.0 International license It is made available under a 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 author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.20.20025510 doi: medRxiv preprint 1 Days from illness onset to admission 6 (4 -9) 6 (4 -9) 6.0 (4 -9) 0.72 6 (4 -8) 6 (4 -8) 0.09 White blood cell count, ×10 9 /L 4.7 (3.6 -6.8) 4.6 (3.6 -6.6) 5. 8 Abbreviations: RT-PCR, reverse transcription polymerase chain reaction; COPD, chronic obstructive pulmonary disease; CT, computed tomography. Data are presented as medians (interquartile ranges, IQR) and n (%). a The disease severity could not be evaluated in 139 patients due to lack of records of SpO 2 . b The SARS-CoV-2 RT-PCR tests were conducted in 199 patients. . It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the The copyright holder for this preprint It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the The copyright holder for this preprint Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia Transmission of SARS-CoV-2 Infection from an Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study New coronavirus pneumonia prevention and control program The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments Outcomes and prognostic factors in 267 patients with severe acute respiratory syndrome in Hong Kong Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Predictive factors for pneumonia development and progression to respiratory failure in MERS-CoV infected patients Clinical, laboratory and radiologic characteristics of 2009 pandemic influenza A/H1N1 pneumonia: primary influenza pneumonia versus concomitant/secondary bacterial pneumonia Markers of treatment failure in hospitalised International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity The copyright holder for this preprint Asymptomatic Contact in Germany. N Engl J Med 2020; published online Jan 30. DOI: 10 .1056/NEJMc2001468. Phan . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.20.20025510 doi: medRxiv preprint 1 8. CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.is the (which was not peer-reviewed) The copyright holder for this preprint .