Abstract
This systematic review and meta-analysis investigated the comorbidities, symptoms, clinical characteristics and treatment of COVID-19 patients. Epidemiological studies published in 2020 (from January–March) on the clinical presentation, laboratory findings and treatments of COVID-19 patients were identified from PubMed/MEDLINE and Embase databases. Studies published in English by 27th March, 2020 with original data were included. Primary outcomes included comorbidities of COVID-19 patients, their symptoms presented on hospital admission, laboratory results, radiological outcomes, and pharmacological and in-patient treatments. 76 studies were included in this meta-analysis, accounting for a total of 11,028 COVID-19 patients in multiple countries. A random-effects model was used to aggregate estimates across eligible studies and produce meta-analytic estimates. The most common comorbidities were hypertension (18.1%, 95% CI 15.4–20.8%). The most frequently identified symptoms were fever (72.4%, 95% CI 67.2–77.7%) and cough (55.5%, 95% CI 50.7–60.3%). For pharmacological treatment, 63.9% (95% CI 52.5–75.3%), 62.4% (95% CI 47.9–76.8%) and 29.7% (95% CI 21.8–37.6%) of patients were given antibiotics, antiviral, and corticosteroid, respectively. Notably, 62.6% (95% CI 39.9–85.4%) and 20.2% (95% CI 14.6–25.9%) of in-patients received oxygen therapy and non-invasive mechanical ventilation, respectively. This meta-analysis informed healthcare providers about the timely status of characteristics and treatments of COVID-19 patients across different countries.
PROSPERO Registration Number: CRD42020176589
Subject terms: Microbiology, Diseases, Health care, Medical research, Risk factors
Introduction
Following the possible patient zero of coronavirus infection identified in early December 20191, the Coronavirus Disease 2019 (COVID-19) has been recognized as a pandemic in mid-March 20202, after the increasing global attention to the exponential growth of confirmed cases3. As on 29th March, 2020, around 690 thousand persons were confirmed infected, affecting 199 countries and territories around the world, in addition to 2 international conveyances: the Diamond Princess cruise ship harbored in Yokohama, Japan, and the Holland America's MS Zaandam cruise ship. Overall, more than 32 thousand died and about 146 thousand have recovered4.
A novel bat-origin virus, 2019 novel coronavirus, was identified by means of deep sequencing analysis. SARS-CoV-2 was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%)5, both of which were respectively responsible for two zoonotic human coronavirus epidemics in the early twenty-first century. Following a few initial human infections6, the disease could easily be transmitted to a substantial number of individuals with increased social gathering7 and population mobility during holidays in December and January8. An early report has described its high infectivity9 even before the infected becomes symptomatic10. These natural and social factors have potentially influenced the general progression and trajectory of the COVID-19 epidemiology.
By the end of March 2020, there have been approximately 3000 reports about COVID-1911. The number of COVID-19-related reports keeps growing everyday, yet it is still far from a clear picture on the spectrum of clinical conditions, transmissibility and mortality, alongside the limitation of medical reports associated with reporting in real time the evolution of an emerging pathogen in its early phase. Previous reports covered mostly the COVID-19 patients in China. With the spread of the virus to other continents, there is an imminent need to review the current knowledge on the clinical features and outcomes of the early patients, so that further research and measures on epidemic control could be developed in this epoch of the pandemic.
Methods
Search strategy and selection criteria
The systematic review was conducted according to the protocol registered in the PROSPERO database (CRD42020176589). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline throughout this review, data were identified by searches of MEDLINE, Embase and references from relevant articles using the search terms "COVID", “SARS-CoV-2”, and “novel coronavirus” (Supplementary material 1). Articles published in English up to 27th March, 2020 were included. National containment measures have been implemented at many countries, irrespective of lockdown, curfew, or stay-at-home orders, since the mid of March 202012, except for China where imposed Hubei province lockdown at 23th January 2020, Studies with original data including original articles, short and brief communication, letters, correspondences were included. Editorials, viewpoints, infographics, commentaries, reviews, or studies without original data were excluded. Studies were also excluded if they were animal studies, modelling studies, or did not measure symptoms presentation, laboratory findings, treatment and therapeutics during hospitalization.
After the removal of duplicate records, two reviewers (CW and CHA) independently screened the eligibility criteria of study titles, abstracts and full-texts, and reference lists of the studies retrieved by the literature search. Disagreements regarding the procedures of database search, study selection and eligibility were resolved by discussion. The second and the last authors (JW and AW) verified the eligibility of included studies.
Outcomes definitions
Signs and symptoms were defined as the presentation of fever, cough, sore throat, headache, dyspnea, muscle pain, diarrhea, rhinorrhea, anosmia, and ageusia at the hospital admission13.
Laboratory findings included a complete blood count (white blood count, neutrophil, lymphocyte, platelet count), procalcitonin, prothrombin time, urea, and serum biochemical measurements (including electrolytes, renal-function and liver-function values, creatine kinase, lactate dehydrogenase, C-reactive protein, Erythrocyte sedimentation rate), and treatment measures (i.e. antiviral therapy, antibiotics, corticosteroid therapy, mechanical ventilation, intubation, respiratory support, and renal replacement therapy). Radiological outcomes included bilateral involvement identified and pneumonia identified by chest radiograph.
Comorbidities of patients evaluated in this study were hypertension, diabetes, chronic obstructive pulmonary disease (COPD), cardiovascular disease, chronic kidney disease, liver disease and cancer.
In-patient treatment included intensive care unit admission, oxygen therapy, non-invasive ventilation, mechanical ventilation, Extracorporeal membrane oxygenation (ECMO), renal replacement therapy, and pharmacological treatment. Use of antiviral and interferon drugs (Lopinavir/ritonavir, Ribavirin, Umifenovir, Interferon-alpha, or Interferon-beta), antibiotic drugs, corticosteroid, and inotropes (Nor-adrenaline, Adrenaline, Vasopressin, Phenylephrine, Dopamine, or Dobutamine) were considered.
Data analysis
Three authors (CW, EHMT and CHA) extracted data using a standardized spreadsheet to record the article type, country of origin, surname of first author, year of publications, sample size, demographics, comorbidities, symptoms, laboratory and radiology results, pharmacological and non-pharmacological treatments.
We aggregated estimates across 90 eligible studies to produce meta-analytic estimates using a random-effects model. For dichotomous outcomes, we estimated the proportion and its respective 95% confidence interval. For laboratory parameters as continuous outcomes, we estimated the mean and standard deviation from the median and interquartile range if the mean and standard deviation were not available from the study14, and calculated the mean and its respective 95% confidence intervals. Random-effect models on DerSimonian and Laird method were adopted due to the significant heterogeneity, checked by the I2 statistics and the p values. I2 statistic of < 25%, 25–75% and ≥ 75% is considered as low, moderate, high likelihood of heterogeneity. Pooled estimates were calculated and presented by using forest plots. Publication bias was estimated by Egger’s regression test. Funnel plots of outcomes were also presented to assess publication bias.
All statistical analyses were conducted using the STATA Version 13.0 (Statacorp, College Station, TX). The random effects model was generated by the Stata packages ‘Metaprop’ for proportions15 and ‘Metan’ for continuous variables16.
Results
The selection and screen process are presented in Fig. 1. A total of 241 studies were found by our searching strategy (71 in PubMed and 170 in Embase). 46 records were excluded due to duplication. After screening the abstracts and titles, 100 English studies were with original data and included in full-text screening. By further excluding 10 studies with not reporting symptoms presentation, laboratory findings, treatment and therapeutics, 90 studies17–106 and 76 studies with more than one COVID-19 case17–31,34–39,42–45,49–51,53,57–64,67,69,70,72–79,81–96,98,100–105 were included in the current systematic review and meta-analysis respectively. 73.3%66 studies were conducted in China. Newcastle–Ottawa Quality Assessment Scale has been used to assess study quality of each included cohort study107. 30% (27/90) of included studies had satisfactory or good quality. The summary of the included study is shown in Table 1.
Figure 1.
PRISMA flowchart reporting identification, searching and selection processes.
Table 1.
Summary of 90 reviewed studies.
Study | Region/country | State/city | Hospital | Period of confirmed cases | N | Mean age (SD) (year) | Male (%) | Severe (%) |
---|---|---|---|---|---|---|---|---|
Xu et al.17 | China | Guangzhou city | Guangzhou Eighth People’s Hospital | 23 Jan 2020—4 Feb 2020 | 90 | 51.3 (NA) | 43.3% | NA |
Cao et al.18 | China | Wuhan city | Zhongnan Hospital | 3 Jan 2020–1 Feb 2020 | 102 | 52.7 (22.6) | 52.0% | NA |
Xiong et al.19 | China | Wuhan city | Tongji hospital | 11 Jan 2020–5 Feb 2020 | 42 | 49.5 (14.1) | 59.5% | NA |
Arentz et al.20 | US | Washington State | Evergreen Hospital | 20 Feb 2020–5 Mar 2020 | 21 | NA | 52.4% | 71.4% |
Huang et al.21 | China | Wuhan city | Jin Yin-tan Hospital | 16 Dec 2019–2 Jan 2020 | 41 | 49.3 (13.1) | 73.2% | NA |
Guan et al.22 | China |
30 provinces, autonomous regions, and municipalities in mainland China |
11 Dec 2019–29 Jan 2020 | 1099 | 46.7 (17.1) | 58.0% | 15.7% | |
Zhao et al.23 | China | Anhui province | Second Affiliated Hospital of Anhui Medical University and Suzhou Municipal Hospital | 23 Jan 2020–5 Feb 2020 | 19 | 43.7 (23.2) | 57.9% | 0.0% |
Xu et al.24 | China | Zhejiang province | Seven hospitals | 10 Jan 2020–26 Jan 2020 | 62 | 41.7 (15.2) | 56.5% | NA |
Chan et al.25 | China | Guangdong province | The University of Hong Kong-Shenzhen Hospital | 10 Jan 2020–15 Jan 2020 | 7 | 46.2 (22.5) | 50.0% | NA |
Chen et al.26 | China | Wuhan city | Jin Yin-tan Hospital | 1 Jan 2020–20 Jan 2020 | 99 | 55.5 (13.1) | 67.7% | 17.2% |
Pung et al.27 | Singapore | Singapore | Not reported | 3 Feb 2020- 8 Feb 2020 | 17 | 42.3 (12.1) | 41.2% | NA |
Wang et al.28 | China | Wuhan city | Zhongnan Hospital | 1 Jan 2020–28 Jan 2020 | 138 | 55.3 (19.5) | 54.3% | 19.6% |
Young et al.29 | Singapore | Singapore | Four hospitals | 23 Jan 2020–3 Feb 2020 | 18 | NA | 50.0% | 0.0% |
Chen et al.30 | China | Wuhan city | Zhongnan Hospital | 20 Jan 2020–31 Jan 2020 | 9 | 32.0 (12.2) | NA | 0.0% |
Huang et al.31 | Taiwan | Taichung | Taichung Veterans General Hospital | NA | 2 | 73.5 (0.5) | 0.0% | NA |
Cheng et al.32 | Taiwan | Taoyuan | Taoyuan General Hospital | 20 Jan 2020 | 1 | 55.0 (NA) | 0.0% | NA |
Holshue et al.33 | US | Washington | Not reported | 20 Jan 2020 | 1 | 35.0 (NA) | 100.0% | NA |
Wei et al.34 | China | Beijing city, Hainan, Guangdong, Anhui, Shanghai, Zhejiang, and Guizhou province | Not reported | 8 Dec 2019–6 Feb 2020 | 9 | 0.5 (0.8) | 22.2% | 0.0% |
Bernard-Stoecklin et al.35 | France | Bordeaux and Paris | Not reported | 10 Jan 2020–24 Jan 2020 | 3 | 36.3 (10.1) | 66.7% | NA |
Shi et al.36 | China | Wuhan city | Jin Yin-tan hospital and Union Hospital of Tongji Medical College | 20 Dec 2019–23 Jan 2020 | 81 | 49.5 (11.0) | 51.9% | 3.7% |
Zhu et al.37 | China | Wuhan city | Jin Yin-tan Hospital | 27 Dec 2019 | 3 | 47.3 (14.6) | 66.7% | 100.0% |
Ghinai et al.38 | US | Illinois State | Not reported | 20 Jan 2020–24 Jan 2020 | 2 | NA | 50.0% | NA |
Zhou et al.39 | China | Wuhan city | Jin Yin-tan Hospital and Wuhan Pulmonary Hospital | 29 Dec 2019–31 Jan 2020 | 191 | 56.3 (15.7) | 62.3% | 62.3% |
Yang et al.70 | China | Wuhan city | Wuhan Jin Yin-tan | 24 Dec 2019–26 Jan 2020 | 52 | 59.7 (13.3) | 67.3% | 100.0% |
Kim et al.41 | South Korea | Seoul | Incheon Medical Center, Seoul National University Hospital, and Seoul National University Bundang Hospital | 21 Feb 2020 | 1 | 35.0 (NA) | 0.0% | NA |
Okada et al.42 | Thailand | Nonthaburi | Bamrasnaradura Infectious Disease Institute Hospital | 8 Jan 2020–13 Jan 2020 | 2 | NA | 0.0% | 0.0% |
Arashiro et al.43 | Diamond Princess cruise ship | 9 Feb 2020 | 2 | 31.0 (14.2) | 50.0% | 0.0% | ||
Lillie et al.44 | UK | Newcastle and Hull | Castle Hill Hospital | 30 Jan 2020 | 2 | 36.5 (19.1) | 50.0% | NA |
Tian et al.45 | China | Wuhan city | Zhongnan Hospital | NA | 2 | 78.5 (19.5) | 50.0% | NA |
Haveri et al.46 | Finland | Rovaniemi | Lapland Central Hospital | 29 Jan 2020 | 1 | NA | 0.0% | NA |
Nicastri et al.47 | Italy | Rome | Lazzaro Spallanzani National Institute for Infectious Diseases | 6 Feb 2020 | 1 | NA | 100.0% | NA |
Cuong et al.48 | Vietnam | Hanoi | Thanh Hoa General Hospital | 1 | 25.0 (NA) | 0.0% | NA | |
Spiteri et al.49 | European region | Germany, France, Italy, Spain, Finland, Sweden, Belgium, Russia | Not reported | 24 Jan 2020–21 Feb 2020 | 38 | 41.7 (NA) | 65.8% | NA |
Rothe et al.50 | Germany | Munich | 26 Jan 2020–28 Jan 2020 | 4 | NA | NA | 0.0% | |
Tong et al.51 | China | Zhejiang Province | Not reported | 19 Jan 2020–30 Jan 2020 | 7 | 31.1 (12.2) | 42.9% | NA |
Bai et al.82 | China | Anyang city | Fifth People’s Hospital of Anyang | 26 Jan 2020–28 Jan 2020 | 5 | NA | 0.0% | 40.0% |
Yu et al.53 | China | Shanghai city | Not reported | 22 Jan 2020–23 Jan 2020 | 4 | 76.5 (25.1) | 50.0% | NA |
Li et al.84 | China | Zhejiang Province | Not reported | 6 Feb 2020–9 Feb 2020 | 4 | 44.8 (27.4) | 25.0% | NA |
Tang et al.55 | China | Zhejiang Province | Not reported | 1 Feb 2020 | 1 | 10.0 (NA) | 100.0% | NA |
Kam et al.56 | Singapore | Singapore | KK Women’s and Children’s Hospital | 3 Feb 2020 | 1 | 0.5 (NA) | 100.0% | NA |
Zhou et al.57 | China | Wuhan city | Tongji Hospital | 16 Jan 2020–30 Jan 2020 | 62 | 52.8 (12.2) | 62.9% | NA |
Zhao et al.58 | China | Hunan Province | Four hospitals | NA | 101 | 44.4 (12.3) | 55.4% | 13.9% |
Cheng et al.59 | China | Shanghai city | Ruijin Hospital | 19 Jan 2020–6 Feb 2020 | 11 | 50.4 (15.5) | 72.7% | NA |
Chung et al.60 | China | Guangdong, Jiangxi, and Shandong Provinces | Three hospitals | 18 Jan 2020–27 Jan 2020 | 21 | 51.0 (14.0) | 61.9% | NA |
Liu et al.61 | China | Hubei province | Nine hospital | 30 Dec 2019–24 Jan 2020 | 137 | 55.0 (16.0) | 44.5% | NA |
Chang et al.62 | China | Beijing city | Three hospitals | 16 Jan 2020–29 Jan 2020 | 13 | 38.7 (11.6) | 76.9% | NA |
COVID-19 National Incident Room Surveillance Team63 | Australia | National-wide | Not reported | 20 Jan 2020–14 Mar 2020 | 295 | 45.9 (17.4) | 50.8% | NA |
Pan et al.64 | China | Wuhan city | Union Hospital | 12 Jan 2020–6 Feb 2020 | 21 | 40.0 (9.0) | 28.6% | 0.0% |
Wang et al.65 | China | Wuhan city | Tongji Hospital | 2 Feb 2020 | 1 | 0.0 (NA) | 0.0% | NA |
Bastola et al.66 | Nepal | Kathmandu | Sukraraj Tropical and Infectious Disease Hospital | 14 Jan 2020 | 1 | 32.0 (NA) | 0.0% | NA |
Qiu et al.67 | China | Zhejiang Province | Three hospitals | 17 Jan 2020–1 Mar 2020 | 36 | 8.3 (3.5) | 63.9% | 0.0% |
Zhang et al.98 | China | Wuhan city | No. 7 Hospital of Wuhan | 16 Jan 2020–3 Feb 2020 | 140 | 0.0 (0.0) | 50.7% | 41.4% |
Ye et al.69 | China | Wuhan city | Zhongnan Hospital | 8 Jan 2020–10 Feb 2020 | 5 | 32.4 (5.7) | 40.0% | NA |
Liu et al.70 | China | Shenzhen | Shenzhen Third People’s Hospital | 21 Jan 2020 | 12 | 52.8 (18.6) | 66.7% | 41.7% |
Chen et al.29 | China | Wuhan city | Tongji Hospital | 13 Jan 2020–12 Feb 2020 | 274 | 58.7 (19.4) | 62.4% | 71.5% |
Guan et al.72 | China | 31 province/autonomous regions/provincial municipalities | 575 hospitals | 11 Dec 2019–31 Jan 2020 | 1590 | 48.9 (16.3) | 56.9% | 16.0% |
Wong et al.73 | China | Hong Kong | Queen Mary Hospital, Pamela Youde Nethersole Eastern Hospital, Queen Elizabeth Hospital, and Ruttonjee Hospital | 1 Jan 2020–5 Mar 2020 | 64 | 56.0 (19.0) | 40.6% | NA |
Xu et al.74 | China | Changzhou | Third Hospital of Changzhou | 23 Jan 2020–18 Feb 2020 | 51 | 42.3 (20.8) | 49.0% | 0.0% |
Shen et al.75 | China | Shenzhen | Shenzhen Third People's Hospital | 20 Jan 2020–25 Mar 2020 | 5 | 54.0 (15.2) | 60.0% | 100.0% |
Kimball et al.76 | US | Washington State | Not reported | 13 Mar 2020 | 23 | 80.7 (8.4) | 30.4% | NA |
Centers for Disease Control and Prevention77 | US | 49 states, district of Columbia, and 3 US territories | Not reported | 12 Feb 2020–16 Mar 2020 | 4226 | NA | NA | NA |
Wu et al.78 | China | Jiangsu Province | Three hospitals | 22 Jan 2020–14 Feb 2020 | 80 | 46.1 (15.4) | 48.8% | 3.8% |
Yang et al.79 | China | Wenzhou city | Three hospitals | 17 Jan 2020–10 Feb 2020 | 149 | 45.1 (13.4) | 54.4% | NA |
Zhu et al.80 | China | Wuhan city | Tongji Hospital | 4 Dec 2019 | 1 | 52.0 (NA) | 100.0% | NA |
Zhu et al.81 | China | Hefei | Affiliated Hospital of University of Science and Technology of China | 24 Jan 2020–20 Feb 2020 | 32 | 44.3 (13.2) | 46.9% | NA |
Wu et al.82 | China | Wuhan city | Jinyintan Hospital | 25 Dec 219–26 Jan 2020 | 201 | 51.3 (12.7) | 63.7% | 41.8% |
Wang et al.83 | China | Shanghai | Shanghai Public Health Clinical Center | 21 Jan 2020–24 Jan 2020 | 4 | 44.3 (22.3) | 75.0% | 25.0% |
Wang et al.84 | China | Shenzhen | Shenzhen Third People's Hospital | 11 Jan 2020–29 Feb 2020 | 55 | 39.9 (21.6) | 40.0% | 3.6% |
Wan et al.85 | China | Chongqing | Chongqing University Three Gorges Hospital | 23 Jan 2020–8 Feb 2020 | 135 | 46.0 (14.2) | 53.3% | 29.6% |
Tian et al.86 | China | Beijing | 57 Hospitals | 20 Jan 2020–10 Feb 2020 | 262 | 45.9 (20.8) | 48.5% | 17.6% |
Sun et al.87 | China | Wuhan city | Wuhan Children’s Hospital | 24 Jan 2020–24 Feb 2020 | 8 | 6.8 (6.5) | 75.0% | 100.0% |
Song et al.88 | China | Shanghai | Shanghai Public Health Clinical Center | 20 Jan 2020–27 Jan 2020 | 51 | 49.0 (16.0) | 49.0% | NA |
Hu et al.89 | China | Nanjing, Jiangsu Province | Second Hospital of Nanjing | 28 Jan 2020–9 Feb 2020 | 24 | 38.9 (22.6) | 33.3% | 0.0% |
Qu et al.90 | China | Huizhou | Huizhou Municipal Central Hospital | Jan 2020–Feb 2020 | 30 | 50.5 (22.6) | 53.3% | 10.0% |
Qian et al.91 | China | Zhejiang | Five hospitals | 20 Jan 2020–11 Feb 2020 | 91 | 47.8 (15.4) | 40.7% | 9.9% |
Mo et al.92 | China | Wuhan city | Zhongnan Hospital | 1 Jan 2020–5 Feb 2020 | 155 | 54.0 (18.0) | 55.5% | 59.4% |
Liu et al.93 | China | Wuhan city | Three hospitals | 30 Dec 2019–15 Jan 2020 | 78 | 42.7 (18.1) | 50.0% | 10.3% |
Liu et al.94 | China | Hainan | Hainan General Hospital | 1 Jan 2020–15 Feb 2020 | 56 | 52.1 (14.7) | 55.4% | NA |
Liu et al.95 | China | Hangzhou | Xixi hospital | 22 Jan 2020–11 Feb 2020 | 10 | 43.0 (10.4) | 40.0% | NA |
Liu et al.127 | China | Wuhan City | Union Hospital | 20 Jan 2020–10 Feb 2020 | 15 | 32.0 (5.0) | 0.0% | NA |
Guillen et al.97 | Spain | Not reported | Not reported | 28 Feb 2020 | 1 | 50.0 (NA) | 100.0% | NA |
Dong et al.98 | China | Wuhan City | Zhongnan Hospital of Wuhan University, Wuhan No.7 Hospital and Wuhan Children’s Hospital | NA | 11 | 36.6 (21.5) | 45.5% | 9.1% |
Fan et al.99 | China | Not reported | Not reported | 24 Jan 2020–26 Jan 2020 | 1 | 31.5 (3.5) | 0.0% | NA |
Chen et al.100 | China | Wuhan City | Renmin hospital of Wuhan University | 30 Jan 2020–23 Feb 2020 | 17 | 29.4 (2.9) | 0.0% | NA |
Chen et al.101 | China | Wuhan City |
Zhongnan Hospital of Wuhan University |
2 Jan 2020 | 2 | NA | 0.0% | NA |
Chen et al.102 | China | Shanghai | Shanghai Public Health Clinical Center | 20 Jan 2020–6 Feb 2020 | 249 | 50.3 (20.9) | 50.6% | 10.0% |
Ding et al.103 | China | Wuhan City | Tongji Hospital | NA | 5 | 50.2 (9.8) | 40.0% | NA |
Kong et al.104 | Korea | Not reported | Not reported | 20 Jan 2020–14 Feb 2020 | 28 | 42.6 (NA) | 53.6% | NA |
Li et al.105 | China | Zhengzhou City | Not reported | 5 Feb 2020 | 2 | 4.0 (0.0) | 50.0% | NA |
Ai et al.106 | China | Shanghai | Not reported | 20 Jan 2020 | 1 | 56.0 (NA) | 0.0% | NA |
COVID-19 Coronavirus Disease 2019, US The United States, UK The United Kingdom, SD standard deviation, NA not available.
Of those 90 eligible studies, 11,028 COVID-19 patients were identified and included in the systematic review. More than half of patients (6336, 57.5%) were from mainland China. The pooled mean age was 45.8 (95% CI 38.6–52.5) years and 49.3% (pooled 95% CI 45.6–53.0%) of them were male.
For specific comorbidity status, the most prevalent comorbidity was hypertension (18.1%, 95% CI 15.4–20.8%), followed by cardiovascular disease (11.8%, 95% CI 9.4–14.2%) and diabetes (10.4%, 95% CI 8.7–12.1%). The pooled prevalence (95% CI) of COPD, chronic kidney disease, liver disease and cancer were 2.0% (1.3–2.7%), 5.2% (1.7–8.8%), 2.5% (1.7–3.4%) and 2.1% (1.3–2.8%) respectively. Moderate to substantial heterogeneity between reviewed studies were found, with I2 statistics ranging from 39.4 to 95.9% (p values between < 0.001–0.041), except for liver disease (I2 statistics: 1.7%, p = 0.433). Detailed results for comorbidity status are displayed in Fig. 2.
Figure 2.
Random-effects meta-analytic estimates for comorbidities. (A) Diabetes mellitus, (B) Hypertension, (C) Cardiovascular disease, (D) Chronic obstructive pulmonary disease, (E) Chronic kidney disease, (F) Cancer.
Regarding the symptoms presented at hospital admission, the most frequent symptoms were fever (pooled prevalence: 72.4%, 95% CI 67.2–77.7%) and cough (pooled prevalence: 55.5%, 95% CI 50.7–60.3%). Sore throat (pooled prevalence: 16.2%, 95% CI 12.7–19.7%), dyspnoea (pooled prevalence: 18.8%, 95% CI 14.7–22.8%) and muscle pain (pooled prevalence: 22.1%, 95% CI 18.6–25.5%) were also common symptoms found in COVID-19 patients, but headache (pooled prevalence: 10.5%, 95% CI 8.7–12.4%), diarrhoea (pooled prevalence: 7.9%, 95% CI 6.3–9.6%), rhinorrhoea (pooled prevalence: 9.2%, 95% CI 5.6–12.8%) were less common. However, none of the included papers reported prevalence of anosmia and ageusia. The I2 statistics varied from 68.5 to 97.1% (all p values < 0.001), indicating a high heterogeneity exists across studies. Figure 3 shows the pooled proportion of symptoms of patients presented at hospital.
Figure 3.
Random-effects meta-analytic estimates for presenting symptoms. (A) Fever, (B) Cough, (C) Dyspnoea, (D) Sore throat, (E) Muscle pain, (F) Headache.
For laboratory parameters, white blood cell (pooled mean: 5.31 × 109/L, 95% CI 5.03–5.58 × 109/L), neutrophil (pooled mean: 3.60 × 109/L, 95% CI 3.31–3.89 × 109/L), lymphocyte (pooled mean: 1.11 × 109/L, 95% CI 1.04–1.17 × 109/L), platelet count (pooled mean: 179.5 U/L, 95% CI 172.6–186.3 U/L), aspartate aminotransferase (pooled mean: 30.3 U/L, 95% CI 27.9–32.7 U/L), alanine aminotransferase (pooled mean: 27.0 U/L, 95% CI 24.4–29.6 U/L) and C-reactive protein (CRP) (pooled mean: 22.0 mg/L, 95% CI 18.3–25.8 mg/L) and D-dimer (0.93 mg/L, 95% CI 0.68–1.18 mg/L) were the common laboratory test taken for COVID-19 patients. Above results and other clinical factors are depicted in Fig. 4. Same with the comorbidity status and symptoms, high likelihood of heterogeneity was detected by I2 statistics for a majority of clinical parameters.
Figure 4.
Random-effects meta-analytic estimates for laboratory parameters. (A) White blood cell, (B) Lymphocyte, (C) Neutrophil, (D) C-creative protein, (E) D-dimer, (F) Lactate dehydrogenase.
Figure 5 presents the distribution of the pharmacological treatments received for COVID-19 patients. 10.6% of patients admitted to intensive care units (pooled 95% CI 8.1–13.2%). For drug treatment, 63.9% (pooled 95% CI 52.5–75.3%), 62.4% (pooled 95% CI 47.9–76.8%) and 29.7% (pooled 95% CI 21.8–37.6%) patients used antibiotics, antiviral, and corticosteroid, respectively. 41.3% (pooled 95% CI 14.3–68.3%) and 50.7% (pooled 95% CI 9.2–92.3%) reported using Lopinavir/Ritonavir and interferon-alpha as antiviral drug treatment, respectively. Among 14 studies reporting proportion of corticosteroid used, 7 studies (50%) specified the formulation of corticosteroid as systemic corticosteroid. The remaining one specified the use of methylprednisolone. No reviewed studies reported the proportion of patients receiving Ribavirin, Interferon-beta, or inotropes.
Figure 5.
Random-effects meta-analytic estimates for pharmacological treatments and intensive unit care at hospital. (A) Antiviral or interferon drugs, (B) Lopinavir/Ritonavir, (C) Interferon alpha (IFN-α), (D) Antibiotic drugs, (E) Corticosteroid, (F) Admission to Intensive care unit.
The prevalence of radiological outcomes and non-pharmacological treatments were presented in Fig. 6. Radiology findings detected chest X-ray abnormalities, with 74.4% (95% CI 67.6–81.1%) of patients with bilateral involvement and 74.9% (95% CI 68.0–81.8%) of patients with viral pneumonia. 62.6% (pooled 95% CI 39.9–85.4%), 20.2% (pooled 95% CI 14.6–25.9%), 15.3% (pooled 95% CI 11.0–19.7%), 1.1% (pooled 95% CI 0.4–1.8%) and 4.7% (pooled 95% CI 2.1–7.4%) took oxygen therapy, non-invasive ventilation, mechanical ventilation, ECMO and dialysis respectively.
Figure 6.
Random-effects meta-analytic estimates for radiological findings and non-pharmacological treatments at hospital. (A) Bilateral involvement, (B) Pneumonia, (C) Oxygen therapy, (D) Non-invasive ventilation, (E) Extracorporeal membrane oxygenation (ECMO), (F) Dialysis.
The funnel plots and results Egger’s test of comorbidity status, symptoms presented, laboratory test and treatment were presented in eFigure 1–S5 in the Supplement. 63% (19/30) of the funnel plots (eFigure 1–S5) showed significance in the Egger’s test for asymmetry, suggesting the possibility of publication bias or small-study effects caused by clinical heterogeneity.
Discussion
This meta-analysis reveals the condition of global medical community responding to COVID-19 in the early phase. During the past 4 months, a new major epidemic focus of COVID-19, some without traceable origin, has been identified. Following its first identification in Wuhan, China, the virus has been rapidly spreading to Europe, North America, Asia, and the Middle East, in addition to African and Latin American countries. Three months since Wuhan CDC admitted that there was a cluster of unknown pneumonia cases related to Huanan Seafood Market and a new coronavirus was identified as the cause of the pneumonia108, as on 1 April, 2020, there have been 858,371 persons confirmed infected with COVID-19, affecting 202 countries and territories around the world. Although this rapid review is limited by the domination of reports from patients in China, and the patient population is of relative male dominance reflecting the gender imbalance of the Chinese population109, it provides essential information.
In this review, the pooled mean age was 45.8 years. Similar to the MERS-CoV pandemic110, middle-aged adults were the at-risk group for COVID-19 infections in the initial phase, which was different from the H1N1 influenza pandemic where children and adolescents were more frequently affected111. Biological differences may affect the clinical presentations of infections; however, in this review, studies examining the asymptomatic COVID-19 infections or reporting any previous infections were not included. It is suggested that another systematic review should be conducted to compare the age-specific incidence rates between the pre-pandemic and post-pandemic periods, so as to understand the pattern and spread of the disease, and tailor specific strategies in infection control.
Both sexes exhibited clinical presentations similar in symptomatology and frequency to those noted in other severe acute respiratory infections, namely influenza A H1N1112 and SARS113,114. These generally included fever, new onset or exacerbation of cough, breathing difficulty, sore throat and muscle pain. Among critically ill patients usually presented with dyspnoea and chest tightness22,29,39,72, 141 (4.6%) of them with persistent or progressive hypoxia resulted in the requirement of intubation and mechanical ventilation115, while 194 (6.4%) of them required non-invasive ventilation, yielding a total of 11% of patients requiring ventilatory support, which was similar to SARS116.
The major comorbidities identified in this review included hypertension, cardiovascular diseases and diabetes mellitus. Meanwhile, the percentages of patients with chronic renal diseases and cancer were relatively low. These chronic conditions influencing the severity of COVID-19 had also been noted to have similar effects in other respiratory illnesses such as SARS, MERS-CoV and influenza117,118. Higher mortality had been observed among older patients and those with comorbidities.
Early diagnosis of COVID-19 was based on recognition of epidemiological linkages; the presence of typical clinical, laboratory, and radiographic features; and the exclusion of other respiratory pathogens. The case definition had initially been narrow, but was gradually broadened to allow for the detection of more cases, as milder cases and those without epidemiological links to Wuhan or other known cases had been identified119,120. Laboratory investigations among COVID-19 patients did not reveal specific characteristics—lymphopenia and elevated inflammatory markers such as CRP are some of the most common haematological and biochemical abnormalities, which had also been noticed in SARS121. None of these features were specific to COVID-19. Therefore, diagnosis should be confirmed by SARS-CoV–2 specific microbiological and serological studies, although initial management will continue to be based on a clinical and epidemiological assessment of the likelihood of a COVID-19 infection.
Radiology imaging often plays an important role in evaluating patients with acute respiratory distress; however, in this review, radiological findings of SARS-CoV-2 pneumonia were non-specific. Despite chest radiograph usually revealed bilateral involvement and Computed Tomography usually showed bilateral multiple ground-glass opacities or consolidation, there were also patients with normal chest radiograph, implying that chest radiograph might not have high specificity to rule out pneumonia in COVID-19.
Limited clinical data were available for asymptomatic COVID-19 infected persons. Nevertheless, asymptomatic infection could be unknowingly contagious122. From some of the official figures, 6.4% of 150 non-travel-related COVID-19 infections in Singapore123, 39.9% of cases from the Diamond Princess cruise ship in Japan124, and up to 78% of cases in China as extracted on April 1st, 2020, were found to be asymptomatic122. 76% (68/90) studies based on hospital setting which provided care and disease management to symptomatic patients had limited number of asymptomatic cases of COVID-19 infection. This review calls for further studies about clinical data of asymptomatic cases. Asymptomatic infection intensifies the challenges of isolation measures. More global reports are crucially needed to give a better picture of the spectrum of presentations among all COVID-19 infected persons. Also, public health policies including social and physical distancing, monitoring and surveillance, as well as contact tracing, are necessary to reduce the spread of COVID-19.
Concerning potential treatment regime, 62.4% of patients received antivirals or interferons (including oseltamivir, lopinavir-ritonavir, interferon alfa), while 63.9% received antibiotics (such as moxifloxacin, and ceftriaxone). In this review, around one-third of patients were given steroid, suggestive as an adjunct to IFN, or sepsis management. Interferon and antiviral agents such as ribavirin, and lopinavir-ritonavir were used during SARS, and the initial uncontrolled reports then noted resolution of fever and improvement in oxygenation and radiographic appearance113,125,126, without further evidence on its effectiveness. At the time of manuscript preparation, there has been no clear evidence guiding the use of antivirals127. Further research is needed to inform clinicians of the appropriate use of antivirals for specific groups of infected patients.
Limitations of this meta-analysis should be considered. First, a high statistical heterogeneity was found, which could be related to the highly varied sample sizes (9 to 4226 patients) and study designs. Second, variations of follow-up period may miss the event leading to heterogeneity. In fact, some patients were still hospitalized in the included studies. Third, since only a few studies had compared the comorbidities of severe and non-severe patients, sensitivity analysis and subgroup analysis were not conducted. Fourthly, the frequency and severity of signs and symptoms reported in included studies, primarily based on hospitalized COVID-19 patients were over-estimated. Moreover, different cutoffs for abnormal laboratory findings were applied across countries, and counties within the same countries. Lastly, this meta-analysis reviewed only a limited number of reports written in English, with a predominant patient population from China. This review is expected to inform clinicians of the epidemiology of COVID-19 at this early stage. A recent report estimated the number of confirmed cases in China could reach as high as 232,000 (95% CI 161,000, 359,000) with the case definition adopted in 5th Edition. In this connection, further evidence on the epidemiology is in imminent need.
Supplementary information
Acknowledgements
None.
Author contributions
C.W., J.W. and A.W. contributed equally to all aspects of study design, conduct, data interpretation, and the writing of the manuscript. C.W., E.T. and C.H.A. contributed to eligibility screening, data extraction from eligible studies, and data analysis and interpretation.
Funding
There was no funding source for this study.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
These authors contributed equally: Carlos K. H. Wong and Janet Y. H. Wong.
Supplementary information
is available for this paper at 10.1038/s41598-020-74988-9.
References
- 1.Oliveira N. Shrimp vendor identified as possible coronavirus ‘patient zero,’ leaked document says. 27 March 2020. New York Daily News. 2020.
- 2.World Health Organization. Basic protective measures against the new coronavirus (2020). https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public. Accessed 7 Oct 2020.
- 3.Google Trend. When will coronavirus end (2020). https://trends.google.com/trends/explore?date=today%203-m&q=when%20will%20coronavirus%20end,%2Fm%2F01cpyy. Accessed 10 Oct 2020.
- 4.Worldometer. COVID-19 Coronavirus Pandemic (2020). https://www.worldometers.info/coronavirus/. Accessed 13 Oct 2020.
- 5.Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565–574. doi: 10.1016/S0140-6736(20)30251-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Ralph R, Lew J, Zeng T, Francis M, Xue B, Roux M, et al. 2019-nCoV (Wuhan virus), a novel Coronavirus: human-to-human transmission, travel-related cases, and vaccine readiness. J. Infect. Dev. Ctries. 2020;14(1):3–17. doi: 10.3855/jidc.12425. [DOI] [PubMed] [Google Scholar]
- 7.Sun Z, Thilakavathy K, Kumar SS, He G, Liu SV. Potential factors influencing repeated SARS outbreaks in China. Int. J. Environ. Res. Public Health. 2020;17(5):1633. doi: 10.3390/ijerph17051633. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Zhao S, Zhuang Z, Ran J, Lin J, Yang G, Yang L, et al. The association between domestic train transportation and novel coronavirus (2019-nCoV) outbreak in China from 2019 to 2020: a data-driven correlational report. Travel Med. Infect. Dis. 2020;33:101568. doi: 10.1016/j.tmaid.2020.101568. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N. Engl. J. Med. 2020;382(13):1199–1207. doi: 10.1056/NEJMoa2001316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Chen J. Pathogenicity and transmissibility of 2019-nCoV-A quick overview and comparison with other emerging viruses. Microbes Infect. 2020;22(2):69–71. doi: 10.1016/j.micinf.2020.01.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.World Health Organization. Database of publications on coronavirus disease (COVID-19) (2020). https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov. Accessed 30 Mar 2020.
- 12.Wong CKH, Wong JYH, Tang EHM, Au CH, Lau KTK, Wai AKC. Impact of national containment measures on decelerating the increase in daily new cases of COVID-19 in 54 countries and 4 epicenters of the pandemic: comparative observational study. J. Med. Internet Res. 2020;22(7):e19904. doi: 10.2196/19904. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19). Symptoms of Coronavirus (2020).
- 14.Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med. Res. Methodol. 2014;14(1):135. doi: 10.1186/1471-2288-14-135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata command to perform meta-analysis of binomial data. Arch. Public Health. 2014;72(1):39. doi: 10.1186/2049-3258-72-39. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Harris RJ, Bradburn MJ, Deeks JJ, Harbord RM, Altman DG, Sterne JAC. metan: fixed- and random-effects meta-analysis. Stata J. 2008;8(1):3–28. doi: 10.1177/1536867X0800800102. [DOI] [Google Scholar]
- 17.Xu X, Yu C, Qu J, Zhang L, Jiang S, Huang D, et al. Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2. Eur. J. Nucl. Med. Mol. Imaging. 2020;47(5):1275–1280. doi: 10.1007/s00259-020-04735-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Cao J, Hu X, Cheng W, Yu L, Tu WJ, Liu Q. Clinical features and short-term outcomes of 18 patients with corona virus disease 2019 in intensive care unit. Intensive Care Med. 2020;46(5):851–853. doi: 10.1007/s00134-020-05987-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Xiong Y, Sun D, Liu Y, Fan Y, Zhao L, Li X, et al. Clinical and high-resolution CT features of the COVID-19 infection: comparison of the initial and follow-up changes. Invest. Radiol. 2020;55(6):332–339. doi: 10.1097/RLI.0000000000000674. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington state. JAMA. 2020;323(16):1612–1614. doi: 10.1001/jama.2020.4326. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 2020;382(18):1708–1720. doi: 10.1056/NEJMoa2002032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Zhao D, Yao F, Wang L, Zheng L, Gao Y, Ye J, et al. A comparative study on the clinical features of coronavirus 2019 (COVID-19) pneumonia with other pneumonias. Clin. Infect. Dis. 2020;71(15):756–761. doi: 10.1093/cid/ciaa247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ. 2020;19(368):m606. doi: 10.1136/bmj.m606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020;395(10223):514–523. doi: 10.1016/S0140-6736(20)30154-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513. doi: 10.1016/S0140-6736(20)30211-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Pung R, Chiew CJ, Young BE, Chin S, Chen MI, Clapham HE, et al. Investigation of three clusters of COVID-19 in Singapore: implications for surveillance and response measures. Lancet. 2020;395(10229):1039–1046. doi: 10.1016/S0140-6736(20)30528-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–1069. doi: 10.1001/jama.2020.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA. 2020;323(15):1488–1494. doi: 10.1001/jama.2020.3204. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395(10226):809–815. doi: 10.1016/S0140-6736(20)30360-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Huang WH, Teng LC, Yeh TK, Chen YJ, Lo WJ, Wu MJ, et al. 2019 novel coronavirus disease (COVID-19) in Taiwan: reports of two cases from Wuhan, China. J. Microbiol. Immunol. Infect. 2020;53(3):481–484. doi: 10.1016/j.jmii.2020.02.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Cheng SC, Chang YC, Fan Chiang YL, Chien YC, Cheng M, Yang CH, et al. First case of coronavirus disease 2019 (COVID-19) pneumonia in Taiwan. J. Formos. Med. Assoc. 2020;119(3):747–751. doi: 10.1016/j.jfma.2020.02.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al. First case of 2019 novel coronavirus in the United States. N. Engl. J. Med. 2020;382(10):929–936. doi: 10.1056/NEJMoa2001191. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang ZJ. Novel coronavirus infection in hospitalized infants under 1 year of age in China. JAMA. 2020;323(13):1313–1314. doi: 10.1001/jama.2020.2131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Bernard Stoecklin, S. et al. First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020. Euro Surveill. 25(6), 20–26 (2020). [DOI] [PMC free article] [PubMed]
- 36.Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect. Dis. 2020;20(4):425–434. doi: 10.1016/S1473-3099(20)30086-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 2020;382(8):727–733. doi: 10.1056/NEJMoa2001017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Ghinai I, McPherson TD, Hunter JC, Kirking HL, Christiansen D, Joshi K, et al. First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA. Lancet. 2020;395(10230):1137–1144. doi: 10.1016/S0140-6736(20)30607-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062. doi: 10.1016/S0140-6736(20)30566-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir. Med. 2020;8(5):475–481. doi: 10.1016/S2213-2600(20)30079-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Kim JY, Choe PG, Oh Y, Oh KJ, Kim J, Park SJ, et al. The first case of 2019 novel coronavirus pneumonia imported into Korea from Wuhan, China: implication for infection prevention and control measures. J. Korean Med. Sci. 2020;35(5):e61. doi: 10.3346/jkms.2020.35.e61. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Okada, P. et al. Early transmission patterns of coronavirus disease 2019 (COVID-19) in travellers from Wuhan to Thailand, January 2020. Euro Surveill. 25(8), 6–10 (2020). [DOI] [PMC free article] [PubMed]
- 43.Arashiro T, Furukawa K, Nakamura A. COVID-19 in 2 persons with mild upper respiratory tract symptoms on a cruise ship, Japan. Emerg. Infect. Dis. 2020;26(6):1345–1348. doi: 10.3201/eid2606.200452. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44.Lillie PJ, Samson A, Li A, Adams K, Capstick R, Barlow GD, et al. Novel coronavirus disease (Covid-19): the first two patients in the UK with person to person transmission. J. Infect. 2020;80(5):578–606. doi: 10.1016/j.jinf.2020.02.020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary pathology of early-phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J. Thorac. Oncol. 2020;15(5):700–704. doi: 10.1016/j.jtho.2020.02.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.Haveri, A. et al. Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February 2020. Euro Surveill. 25(11), 16–21 (2020). [DOI] [PMC free article] [PubMed]
- 47.Nicastri, E. et al. Coronavirus disease (COVID-19) in a paucisymptomatic patient: epidemiological and clinical challenge in settings with limited community transmission, Italy, February 2020. Euro Surveill. 25(11) (2020). [DOI] [PMC free article] [PubMed]
- 48.Van Cuong L, Giang HTN, Linh LK, Shah J, Van Sy L, Hung TH, et al. The first Vietnamese case of COVID-19 acquired from China. Lancet Infect Dis. 2020;20(4):408–409. doi: 10.1016/S1473-3099(20)30111-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49.Spiteri, G. et al. First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020. Euro Surveill. 25(9), 2–7 (2020). [DOI] [PMC free article] [PubMed]
- 50.Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G, Wallrauch C, et al. Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. N. Engl. J. Med. 2020;382(10):970–971. doi: 10.1056/NEJMc2001468. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.Tong ZD, Tang A, Li KF, Li P, Wang HL, Yi JP, et al. Potential presymptomatic transmission of SARS-CoV-2, Zhejiang Province, China, 2020. Emerg. Infect. Dis. 2020;26(5):1052–1054. doi: 10.3201/eid2605.200198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52.Bai Y, Yao L, Wei T, Tian F, Jin DY, Chen L, et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020;323(14):1406–1407. doi: 10.1001/jama.2020.2565. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53.Yu P, Zhu J, Zhang Z, Han Y. A familial cluster of infection associated with the 2019 novel coronavirus indicating possible person-to-person transmission during the incubation period. J. Infect. Dis. 2020;221(11):1757–1761. doi: 10.1093/infdis/jiaa077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54.Li P, Fu JB, Li KF, Liu JN, Wang HL, Liu LJ, et al. Transmission of COVID-19 in the terminal stages of the incubation period: a familial cluster. Int. J. Infect. Dis. 2020;96:452–453. doi: 10.1016/j.ijid.2020.03.027. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.Tang A, Tong ZD, Wang HL, Dai YX, Li KF, Liu JN, et al. Detection of novel coronavirus by RT-PCR in stool specimen from asymptomatic child, China. Emerg. Infect. Dis. 2020;26(6):1337–1339. doi: 10.3201/eid2606.200301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56.Kam KQ, Yung CF, Cui L, Tzer Pin Lin R, Mak TM, Maiwald M, et al. A well infant with coronavirus disease 2019 with high viral load. Clin. Infect. Dis. 2020;71(15):847–849. doi: 10.1093/cid/ciaa201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 57.Zhou S, Wang Y, Zhu T, Xia L. CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan. China. AJR Am J Roentgenol. 2020;214(6):1287–1294. doi: 10.2214/AJR.20.22975. [DOI] [PubMed] [Google Scholar]
- 58.Zhao W, Zhong Z, Xie X, Yu Q, Liu J. Relation between chest CT findings and clinical conditions of coronavirus disease (COVID-19) pneumonia: a multicenter study. AJR Am. J. Roentgenol. 2020;214(5):1072–1077. doi: 10.2214/AJR.20.22976. [DOI] [PubMed] [Google Scholar]
- 59.Cheng Z, Lu Y, Cao Q, Qin L, Pan Z, Yan F, et al. Clinical features and chest CT manifestations of coronavirus disease 2019 (COVID-19) in a single-center study in Shanghai, China. AJR Am. J. Roentgenol. 2020;215(1):121–126. doi: 10.2214/AJR.20.22959. [DOI] [PubMed] [Google Scholar]
- 60.Chung M, Bernheim A, Mei X, Zhang N, Huang M, Zeng X, et al. CT imaging features of 2019 novel coronavirus (2019-nCoV) Radiology. 2020;295(1):202–207. doi: 10.1148/radiol.2020200230. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 61.Liu K, Fang YY, Deng Y, Liu W, Wang MF, Ma JP, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl). 2020;133(9):1025–1031. doi: 10.1097/CM9.0000000000000744. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 62.Chang LM, Wei L, Xie L, Zhu G, Dela Cruz CS, et al. Epidemiologic and clinical characteristics of novel coronavirus infections involving 13 patients outside Wuhan, China. JAMA. 2020;323(11):1092–1093. doi: 10.1001/jama.2020.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 63.Team C-NIRS. COVID-19, Australia: Epidemiology Report 7 (Reporting week ending 19:00 AEDT 14 March 2020). Commun. Dis. Intell. 44 (2018). [DOI] [PubMed]
- 64.Pan F, Ye T, Sun P, Gui S, Liang B, Li L, et al. Time course of lung changes at chest CT during recovery from coronavirus disease 2019 (COVID-19) Radiology. 2020;295(3):715–721. doi: 10.1148/radiol.2020200370. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 65.Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J, et al. A case report of neonatal 2019 coronavirus disease in China. Clin. Infect. Dis. 2020;71(15):853–857. doi: 10.1093/cid/ciaa225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 66.Bastola A, Sah R, Rodriguez-Morales AJ, Lal BK, Jha R, Ojha HC, et al. The first 2019 novel coronavirus case in Nepal. Lancet Infect. Dis. 2020;20(3):279–280. doi: 10.1016/S1473-3099(20)30067-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 67.Qiu H, Wu J, Hong L, Luo Y, Song Q, Chen D. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. Lancet Infect. Dis. 2020;20(6):689–696. doi: 10.1016/S1473-3099(20)30198-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 68.Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020;75(7):1730–1741. doi: 10.1111/all.14238. [DOI] [PubMed] [Google Scholar]
- 69.Ye G, Pan Z, Pan Y, Deng Q, Chen L, Li J, et al. Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation. J. Infect. 2020;80(5):e14–e17. doi: 10.1016/j.jinf.2020.03.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 70.Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci. China Life Sci. 2020;63(3):364–374. doi: 10.1007/s11427-020-1643-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 71.Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;26(368):m1091. doi: 10.1136/bmj.m1091. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 72.Guan WJ, Liang WH, Zhao Y, Liang HR, Chen ZS, Li YM, et al. Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis. Eur Respir J. 2020;55(5):2000547. doi: 10.1183/13993003.00547-2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 73.Wong HYF, Lam HYS, Fong AH, Leung ST, Chin TW, Lo CSY, et al. Frequency and Distribution of Chest Radiographic Findings in Patients Positive for COVID-19. Radiology. 2020;296(2):E72–E78. doi: 10.1148/radiol.2020201160. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 74.Xu T, Chen C, Zhu Z, Cui M, Chen C, Dai H, et al. Clinical features and dynamics of viral load in imported and non-imported patients with COVID-19. Int J Infect Dis. 2020;94:68–71. doi: 10.1016/j.ijid.2020.03.022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 75.Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA. 2020;323(16):1582–1589. doi: 10.1001/jama.2020.4783. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 76.Kimball A, Hatfield KM, Arons M, James A, Taylor J, Spicer K, et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility—King County, Washington, March 2020. Morb. Mortal. Wkly. Rep. 2020;69(13):377–381. doi: 10.15585/mmwr.mm6913e1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 77.Team CC-R Severe outcomes among patients with coronavirus disease 2019 (COVID-19)—United States, February 12-March 16, 2020. Morb. Mortal. Wkly. Rep. 2020;69(12):343–346. doi: 10.15585/mmwr.mm6912e2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 78.Wu J, Liu J, Zhao X, Liu C, Wang W, Wang D, et al. Clinical characteristics of imported cases of coronavirus disease 2019 (COVID-19) in Jiangsu Province: a multicenter descriptive study. Clin. Infect. Dis. 2020;71(15):706–712. doi: 10.1093/cid/ciaa199. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 79.Yang W, Cao Q, Qin L, Wang X, Cheng Z, Pan A, et al. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China. J. Infect. 2020;80(4):388–393. doi: 10.1016/j.jinf.2020.02.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 80.Zhu L, Xu X, Ma K, Yang J, Guan H, Chen S, et al. Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression. Am. J. Transplant. 2020;20(7):1859–1863. doi: 10.1111/ajt.15869. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 81.Zhu W, Xie K, Lu H, Xu L, Zhou S, Fang S. Initial clinical features of suspected coronavirus disease in two emergency departments outside of Hubei, China. J. Med. Virol. 2019;92:1525–1532. doi: 10.1002/jmv.25763. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 82.Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern. Med. 2020;180(7):934–943. doi: 10.1001/jamainternmed.2020.0994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 83.Wang Z, Chen X, Lu Y, Chen F, Zhang W. Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Biosci. Trends. 2020;14(1):64–68. doi: 10.5582/bst.2020.01030. [DOI] [PubMed] [Google Scholar]
- 84.Wang Y, Liu Y, Liu L, Wang X, Luo N, Li L. Clinical outcomes in 55 patients with severe acute respiratory syndrome coronavirus 2 who were asymptomatic at hospital admission in Shenzhen, China. J. Infect. Dis. 2020;221(11):1770–1774. doi: 10.1093/infdis/jiaa119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 85.Wan S, Xiang Y, Fang W, Zheng Y, Li B, Hu Y, et al. Clinical features and treatment of COVID-19 patients in northeast Chongqing. J. Med.. Virol. 2020;92(7):797–806. doi: 10.1002/jmv.25783. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 86.Tian S, Hu N, Lou J, Chen K, Kang X, Xiang Z, et al. Characteristics of COVID-19 infection in Beijing. J. Infect. 2020;80(4):401–406. doi: 10.1016/j.jinf.2020.02.018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 87.Sun D, Li H, Lu XX, Xiao H, Ren J, Zhang FR, et al. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study. World J. Pediatr. 2020;16(3):251–259. doi: 10.1007/s12519-020-00354-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 88.Song F, Shi N, Shan F, Zhang Z, Shen J, Lu H, et al. Emerging 2019 novel coronavirus (2019-nCoV) pneumonia. Radiology. 2020;295(1):210–217. doi: 10.1148/radiol.2020200274. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 89.Hu Z, Song C, Xu C, Jin G, Chen Y, Xu X, et al. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci. China Life Sci. 2020;63(5):706–711. doi: 10.1007/s11427-020-1661-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 90.Qu R, Ling Y, Zhang YH, Wei LY, Chen X, Li XM, et al. Platelet-to-lymphocyte ratio is associated with prognosis in patients with coronavirus disease-19. J. Med. Virol. 2020;92:1533–1541. doi: 10.1002/jmv.25767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 91.Qian GQ, Yang NB, Ding F, Ma AHY, Wang ZY, Shen YF, et al. Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: a retrospective, multi-centre case series. QJM. 2020;113(7):474–481. doi: 10.1093/qjmed/hcaa089. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 92.Mo, P. et al. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China. Clin. Infect. Dis. (2020).
- 93.Liu W, Tao ZW, Wang L, Yuan ML, Liu K, Zhou L, et al. Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Chin Med. J. (Engl) 2020;133(9):1032–1038. doi: 10.1097/CM9.0000000000000775. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 94.Liu K, Chen Y, Lin R, Han K. Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients. J. Infect. 2020;80(6):e14–e18. doi: 10.1016/j.jinf.2020.03.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 95.Liu F, Xu A, Zhang Y, Xuan W, Yan T, Pan K, et al. Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression. Int. J. Infect. Dis. 2020;95:183–191. doi: 10.1016/j.ijid.2020.03.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 96.Liu D, Li L, Wu X, Zheng D, Wang J, Yang L, et al. Pregnancy and perinatal outcomes of women with coronavirus disease (COVID-19) pneumonia: a preliminary analysis. AJR Am. J. Roentgenol. 2020;215(1):127–132. doi: 10.2214/AJR.20.23072. [DOI] [PubMed] [Google Scholar]
- 97.Guillen E, Pineiro GJ, Revuelta I, Rodriguez D, Bodro M, Moreno A, et al. Case report of COVID-19 in a kidney transplant recipient: does immunosuppression alter the clinical presentation? Am. J. Transplant. 2020;20(7):1875–1878. doi: 10.1111/ajt.15874. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 98.Dong X, Cao YY, Lu XX, Zhang JJ, Du H, Yan YQ, et al. Eleven faces of coronavirus disease 2019. Allergy. 2020;75(7):1699–1709. doi: 10.1111/all.14289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 99.Fan, C. et al. Perinatal transmission of COVID-19 associated SARS-CoV-2: should we worry? Clin. Infect. Dis. (2020).
- 100.Chen R, Zhang Y, Huang L, Cheng BH, Xia ZY, Meng QT. Safety and efficacy of different anesthetic regimens for parturients with COVID-19 undergoing Cesarean delivery: a case series of 17 patients. Can. J. Anaesth. 2020;67(6):655–663. doi: 10.1007/s12630-020-01630-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 101.Chen L, Liu W, Zhang Q, Xu K, Ye G, Wu W, et al. RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak. Emerg. Microbes Infect. 2020;9(1):313–319. doi: 10.1080/22221751.2020.1725399. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 102.Chen J, Qi T, Liu L, Ling Y, Qian Z, Li T, et al. Clinical progression of patients with COVID-19 in Shanghai, China. J. Infect. 2020;80(5):e1–e6. doi: 10.1016/j.jinf.2020.03.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 103.Ding Q, Lu P, Fan Y, Xia Y, Liu M. The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China. J. Med. Virol. 2020;92:1549–1555. doi: 10.1002/jmv.25781. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 104.Covid-19 National Emergency Response Center E. Case Management Team KCfDC, Prevention Early epidemiological and clinical characteristics of 28 cases of coronavirus disease in South Korea. Osong Public Health Res. Perspect. 2020;11(1):8–14. doi: 10.24171/j.phrp.2020.11.1.03. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 105.Li Y, Guo F, Cao Y, Li L, Guo Y. Insight into COVID-2019 for pediatricians. Pediatr. Pulmonol. 2020;55(5):E1–E4. doi: 10.1002/ppul.24734. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 106.Ai JW, Zhang Y, Zhang HC, Xu T, Zhang WH. Era of molecular diagnosis for pathogen identification of unexplained pneumonia, lessons to be learned. Emerg Microbes Infect. 2020;9(1):597–600. doi: 10.1080/22221751.2020.1738905. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 107.Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur. J. Epidemiol. 2010;25(9):603–605. doi: 10.1007/s10654-010-9491-z. [DOI] [PubMed] [Google Scholar]
- 108.Khan N. New virus discovered by Chinese scientists investigating pneumonia outbreak. Wall Street J. (2020).
- 109.国家统计局 (National Bureau of Statistics). 2019 年国民经济运行总体平稳 发展主要预期目标较好实现 (In 2019, the overall stable development of the national economic operation is expected to achieve the main goals (2020). http://www.stats.gov.cn/tjsj/zxfb/202001/t20200117_1723383.html. Accessed 30 Mar 2020.
- 110.Park JE, Jung S, Kim A, Park JE. MERS transmission and risk factors: a systematic review. BMC Public Health. 2018;18(1):574. doi: 10.1186/s12889-018-5484-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 111.Van Kerkhove MD, Vandemaele KA, Shinde V, Jaramillo-Gutierrez G, Koukounari A, Donnelly CA, et al. Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis. PLoS Med. 2011;8(7):e1001053. doi: 10.1371/journal.pmed.1001053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 112.Wang C, Yu E, Xu B, Wang W, Li L, Zhang W, et al. Epidemiological and clinical characteristics of the outbreak of 2009 pandemic influenza A (H1N1) at a middle school in Luoyang, China. Public Health. 2012;126(4):289–294. doi: 10.1016/j.puhe.2011.11.008. [DOI] [PubMed] [Google Scholar]
- 113.Lee N, Hui D, Wu A, Chan P, Cameron P, Joynt GM, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N. Engl. J. Med. 2003;348(20):1986–1994. doi: 10.1056/NEJMoa030685. [DOI] [PubMed] [Google Scholar]
- 114.Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA. 2003;289(21):2801–2809. doi: 10.1001/jama.289.21.JOC30885. [DOI] [PubMed] [Google Scholar]
- 115.Fowler RA, Lapinsky SE, Hallett D, Detsky AS, Sibbald WJ, Slutsky AS, et al. Critically ill patients with severe acute respiratory syndrome. JAMA. 2003;290(3):367–373. doi: 10.1001/jama.290.3.367. [DOI] [PubMed] [Google Scholar]
- 116.Christian MD, Poutanen SM, Loutfy MR, Muller MP, Low DE. Severe acute respiratory syndrome. Clin Infect Dis. 2004;38(10):1420–1427. doi: 10.1086/420743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 117.Mertz D, Kim TH, Johnstone J, Lam PP, Science M, Kuster SP, et al. Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis. BMJ. 2013;23(347):f5061. doi: 10.1136/bmj.f5061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 118.Badawi A, Ryoo SG. Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis. Int. J. Infect. Dis. 2016;49:129–133. doi: 10.1016/j.ijid.2016.06.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 119.Tsang TK, Wu P, Lin Y, Lau EHY, Leung GM, Cowling BJ. Effect of changing case definitions for COVID-19 on the epidemic curve and transmission parameters in mainland China: a modelling study. Lancet Public Health. 2020;5(5):e289–e296. doi: 10.1016/S2468-2667(20)30089-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 120.国家卫生健康委办公厅 (Office of National Health Comission). 新型冠状病毒肺炎诊疗方案 (试行第七版) (Clinical Guideline for Novel Coronavirus Pneumonia—Interim 7th Edition) (2020).
- 121.File TM, Jr, Tsang KW. Severe acute respiratory syndrome: pertinent clinical characteristics and therapy. Treat. Respir. Med. 2005;4(2):95–106. doi: 10.2165/00151829-200504020-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 122.Day M. Covid-19: four fifths of cases are asymptomatic, China figures indicate. BMJ. 2020;2(369):m1375. doi: 10.1136/bmj.m1375. [DOI] [PubMed] [Google Scholar]
- 123.Wei WE, Li Z, Chiew CJ, Yong SE, Toh MP, Lee VJ. Presymptomatic transmission of SARS-CoV-2—Singapore, January 23–March 16, 2020. Morb. Mortal. Wkly. Rep. 2020;69(14):411–415. doi: 10.15585/mmwr.mm6914e1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 124.Mizumoto K, Kagaya K, Zarebski A, Chowell G. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill. 2020;25(10):2000180. doi: 10.2807/1560-7917.ES.2020.25.10.2000180. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 125.Poutanen SM, Low DE, Henry B, Finkelstein S, Rose D, Green K, et al. Identification of severe acute respiratory syndrome in Canada. N. Engl. J .Med. 2003;348(20):1995–2005. doi: 10.1056/NEJMoa030634. [DOI] [PubMed] [Google Scholar]
- 126.Tsang KW, Ho PL, Ooi GC, Yee WK, Wang T, Chan-Yeung M, et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N. Engl. J. Med. 2003;348(20):1977–1985. doi: 10.1056/NEJMoa030666. [DOI] [PubMed] [Google Scholar]
- 127.Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of Lopinavir–Ritonavir in adults hospitalized with severe covid-19. N. Engl. J. Med. 2020;382(19):1787–1799. doi: 10.1056/NEJMoa2001282. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.