key: cord-0776265-kjjlxdpp authors: Fang, Zhangfu; Yi, Fang; Wu, Kang; Lai, Kefang; Sun, Xizhuo; Zhong, Nanshan; Liu, Zhigang title: Clinical Characteristics of Coronavirus Pneumonia 2019 (COVID-19): An Updated Systematic Review date: 2020-03-10 journal: nan DOI: 10.1101/2020.03.07.20032573 sha: 970a28c4a3c1fbcb5322772956955b8c4a3bb257 doc_id: 776265 cord_uid: kjjlxdpp OBJECTIVE Clinical characteristics of novel coronavirus pneumonia (COVID-19) have been described in numerous studies but yielded varying results. We aimed to conduct a systematic review on scientific literatures and to synthesize critical data on clinical traits of COVID-19 from its initial outbreak to pandemic. METHODS Systematic searches were conducted to identify retrospective observational study that contained clinical characteristics on COVID-19 through multiple databases. Two reviewers independently evaluated eligible publications. Data on clinical characteristics of COVID-19 were extracted and analyzed. RESULTS Seventy-two retrospective studies demonstrating the clinical characteristics of COVID-19 were included. A total of 3470 COVID-19 patients were synthesized to the final analysis in an unbiased manner. The most common symptom was fever (2878 [83.0%]), and 63.4% of the patients presented fever as onset symptom. There were 2528 [88.2%] of 2866 cases had abnormal lung findings on chest CT scan. Laboratory findings showed that 1498 [62.8%] of 2387 cases had lymphopenia, and 1354 [64.8%] of 2091 cases had an increased level of C-reactive protein (CRP). A total of 185 [11.5%] patients were admitted to intensive care unit (ICU) while the overall case fatality rate (CFR) was 3.7%. Compared to patients admitted outside of Hubei, China, those from Hubei had a significant higher ICU admission rate (21.9% vs. 2.5%, p<0.001). Also, CFR attributed to COVID-19 was significantly higher in Hubei than that of non-Hubei admissions (10.4% vs. 0.6%, p<0.001). INTERPRETATION This large patient-based systematic review presents a more precise profiling of the COVID-19 from its outbreak to current pandemic. Dynamic evolvements of COVID-19 are needed to be characterized in future studies. COVID-19 among different studies, partly due to anthropogenic differences in patients enrolled and differences in sample size across different studies. Notably, variation in reporting descriptive data may lead to the misunderstanding of COVID-9 characteristics. In this updated systematic review, hence, we sought to address the heterogeneities among published retrospective studies and to synthesize the available data. We expect this critical review will provide insights to understand the clinical characteristics of COVID-19 in a more systematic manner. Systematic searches were performed via the Medline database (PubMed) and Embase combining the terms (novel coronavirus OR 2019 novel coronavirus OR 2019-nCoV OR Coronavirus disease 2019 OR COVID-19 OR SARS-CoV-2). We also searched the database of Chinese Medical Journal full-text database (http://journal.yiigle.com/) for publications in Chinese using the above strategies. Searches were limited to publications from January 1, 2020 to March 1, 2020. Two of the authors (Z. F. and F. Y.) independently screened searching results to determine inclusion or exclusion of the articles. Disagreements were modulated by consulting another author as adjudicator (Z. L.). We included retrospective observational studies as long as they contain clinical characteristics of COVID-19 associated illness. If the patients came from the same hospital with overlapping cases, we only selected the publication containing greatest number of cases. The following All included literatures were evaluated using the Newcastle-Ottawa Scale (NOS) 11 . The quality score of the literature ranged from lowest 0 to highest 9. Total quality score of 0-3, 4-6, and 7-9 indicated poor, fair, and good studies, respectively. Information on baseline demographic data, medical and exposure history, symptoms and signs, underlying comorbidities, laboratory findings, chest computed tomographic (CT) scans and CFR were recorded. Based on the diagnostic gold standard for COVID-19 (positive RT-PCR assay for SARS-CoV-2), we synthesized data on demographic and clinical parameters in an unbiased manner. The proportion of each parameter was calculated by the following formula: (actual patient counts)/ (total patients confirmed using the gold standard) × 100%. The A total of 1052 publications were retrieved using the search strategy. Seventy-two retrospective studies (including 22 case report, 20 case series, 3 case-control and 27 cross-sectional studies) that met the inclusion criteria were included in the final analysis ( Figure 1 ). Of the selected publications, 51 were written in English while 21 were written in Chinese. The general information on eligible publications can be found in Table 1 February 14, 2020 . Quality assessment of the literatures showed that cross-sectional studies achieved a good quality (median score, 7.0) while case report/series were fair (median score, 6.0). A total of 3,470 COVID-19 patients were included, of which 3,468 confirmed cases were based on the positive SARS-CoV-2 on RT-PCR assay while two cases 25 were diagnosed according to coronavirus antibody detections. The age of the COVID-19 patients ranged from 17 days to 92 years old. Male gender accounted for 1822 (52.6%) of the selected patients. Among 1,573 patients who were asked for smoking status, 208 (13.2%) were self-reported smokers. Through a synthesized analysis, a total of 2182 cases (76.0%) had a history of transmission exposures, i.e., the patients were either Wuhan residents or travelled to Wuhan within the past 14 days. The most common symptom of COVID- 19 Table 3 for details). author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . Collectively, a total of 185 [11.5%] patients were admitted to intensive care unit (ICU) while the overall CFR was 3.7% ( Table 2) . Our further analysis showed that COVID-19 patients admitted in Hubei province (Wuhan in particular) suffered from a significant higher ICU admission rate than that outside of Hubei, China (21.9% vs. 2.5%, p<0.001). Also, CFR attributed to COVID-19 in Hubei province, China was significantly higher than that in non-Hubei, China (10.4% vs. 0.6%, p<0.001). author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . indicating that COVID-19 may not have a gender predisposition. Although 13.2% of the selected patients had a history of smoking, we could not draw the conclusion that smokers are less susceptible to the viral infection than non-smokers, as the patients included in our analysis were from a sample pool that was not representative the general population by smoking status. This systematic review showed that most of the patients (76.0%) had a history of Wuhan-related exposures. This is of great importance for early quarantine for the subjects with emerging infectious disease when specific treatments are not available. Actually, we have learned from the SARS outbreak 17 years ago that early identification, early isolation and early management would lead to the stop of viral transmissions from human to human 79 . Collectively, there were 36% of the COVID-19 patients absent from fever as the onset symptom. In this case, such patients may have been ignored at the early stage if we focused heavily on fever examination for initial screening. Our composite analysis showed that fever remains the most common symptom (83.0%) in patients with COVID-19. However, the proportion of fever is somewhat lower than that of other coronavirus related respiratory illness, such as SARS (100%) 80 81 or middle east respiratory syndrome (MERS) (98%) 82 . Similarly, the accompanied symptoms of dyspnea (14.5%) and diarrhea (6.1%) are relatively less common in patients with COVID-19 than those seen in SARS and MERS 52 . More importantly, this study revealed an overall CFR of 3.7%, which was quite similar to that reported by the WHO official statistics as of March 5, 2020 (CFR 3.7%, 3,015 died of 80,565 cases) 4 . Nevertheless, the CFR of COVID-19 was much lower than that of SARS (9.6%) 83 and MERS (37.1%) 84 . By far, the mechanisms underlying the varying symptoms and CFR for these three coronavirus-infected diseases are not fully understood. One reason may be that there were still some COVID-19 patients being treated in hospitals at the time of the manuscripts submitted, so the outcome (death or recovery) is not known yet. Additionally, we suppose that the varied tropism as well as virulence of these three coronaviruses may in part account for the discrepancies, which warrants further All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . author/funder, who has granted medRxiv a license to display the preprint in perpetuity. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . author/funder, who has granted medRxiv a license to display the preprint in perpetuity. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . Report of clustering pneumonia of unknown etiology in Wuhan City WHO. 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