key: cord-267971-xgwmda8e
authors: Tan, Shing Cheng
title: Clinical and epidemiological characteristics of Coronavirus Disease 2019 (COVID-19) patients
date: 2020-04-07
journal: nan
DOI: 10.1101/2020.04.02.20050989
sha: 
doc_id: 267971
cord_uid: xgwmda8e

Background: Numerous groups have reported the clinical and epidemiological characteristics of Coronavirus Disease 2019 (COVID-19) cases; however, the data remained inconsistent. This paper aimed to pool the available data to provide a more complete picture of the characteristics of COVID-19 patients. Methods: A systematic review and pooled analysis was performed. Eligible studies were identified from database and hand searches up to March 2, 2020. Data on clinical (including laboratory and radiological) and epidemiological (including demographic) characteristics of confirmed COVID-19 cases were extracted and combined by simple pooling. Results: Of 644 studies identified, 69 studies (involving 48,926 patients) were included in the analysis. The average age of the patients was 49.16 years. A total of 51.46% of the patients were men and 52.32% were non-smokers. Hypertension (50.82%) and diabetes (20.89%) were the most frequent comorbidities observed. The most common symptoms were fever (83.21%), cough (61.74%), and myalgia or fatigue (30.22%). Altered levels of blood and biochemical parameters were observed in a proportion of the patients. Most of the patients (78.50%) had bilateral lung involvements, and 5.86% showed no CT findings indicative of viral pneumonia. Acute respiratory distress syndrome (28.36%), acute cardiac injury (7.89%) and acute kidney injury (7.60%) were the most common complications recorded. Conclusions: Clinical and epidemiological characteristics of COVID-19 patients were mostly heterogeneous and non-specific. This is the most comprehensive report of the characteristics of COVID-19 patients to date. The information presented is important for improving our understanding of the spectrum and impact of this novel disease.

There is an ongoing pandemic of viral pneumonia called Coronavirus Disease 2019 which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. 44

At the time of this writing, the disease has been reported to affect 634,835 people in more than 45 200 countries, territories or areas, and cause 29,891 deaths (1). Understanding the clinical and 46 epidemiological characteristics of the disease is important for informing public health decision 47 making, which would enable improvement of surveillance and effective planning of treatment. In in China and in other parts of the world (3-12). However, most of these reports were limited by a 52 small sample size, and the characteristics reported appeared to be inconsistent. For example, in 53 a report involving 99 patients, Chen et al.

(3) noted a much higher proportion of men than 54 women, and suggested that men were generally more susceptible to SARS-CoV-2 infection. On 55 the other hand, Shi et al. (4) found that the male-to-female ratio among the 81 patients included 56 was close to 1:1, indicating that both genders were equally susceptible to 57 the World Health Organization (WHO) has declared COVID-19 a global pandemic and the 58 contagion shows no sign of slowing down (13). Thus, it is a timely prompt to obtain a more 59 precise understanding of the disease by combining all available data in the literature. In this 60 study, a systematic review and pooled analysis was performed to characterize the clinical and 61 epidemiological features of COVID-19 patients. 62

Three separate searches were performed on PubMed database on March 2, 2020, using the 65 keywords "COVID-19", "2019-nCoV" and "SARS-CoV-2". No language restriction was applied. 66

After removal of duplicated records, screening by title and abstract was performed to identify 67 potentially relevant studies. The full-texts of these potentially relevant studies were then 68 evaluated. The reference lists of these studies were also hand-searched to identify additional 69 records. Studies were included if they reported any clinical and/or epidemiological data of 70 confirmed COVID-19 patients, regardless of their study design. However, review papers or 71 studies employing secondary analysis of the previously available data were excluded from the 72 analysis. In case of overlapping studies, the ones which the largest sample size or the most 73 complete data set were included. 74 75

The following data were extracted from the included studies: name of first author, country, date 77 of diagnosis, demographic data, smoking status, comorbidities, signs and symptoms, 78 laboratory/biochemical data, CT findings, and complications of the disease. A simple pooling of 79 data was performed to provide an overall summary of the clinical and epidemiological 80 characteristics of the patients. All data are reported as absolute number and/or mean. As 81 patient-level data were not available in majority of the studies, standard deviation could not be 82 calculated. 83 84

There was no funding source for this study. The corresponding author had full access to all the 86 data in the study and had final responsibility for the decision to submit for publication. 87

The flowchart of study selection is depicted in Figure 1 . A total of 644 records were identified 89 showed decreased and increased leukocyte counts. Besides, 51.39% of the patients had a 114 decreased lymphocyte count and 9.63% had a decreased platelet count. Increased levels of 115 aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, hypersensitive 116 troponin I, procalcitonin and C-reactive protein were observed in 27. 45%, 5.19%, 13.25%, 117 45.76%, 3.57%, 69.08% and 72.30% of the patients, respectively. 118 119 Analysis of computed tomography (CT) data revealed that most of the patients (78.50%) 120 had bilateral lung involvements, while 15.65% had unilateral lung involvements and 5.86% 121 showed no sign of viral pneumonia. In 41.18% of the patients, all five lung lobes were affected. 122

On the other hand, as much as 17.03%, 11.46%, 12.69% and 17.65% patients respectively had 123 one, two, three and four lobes affected. 124 125 It was unknown how many patients had complications following SARS-CoV-2 infection. 126

Nonetheless, among the wide spectrum of complications observed, acute respiratory distress 127 syndrome (ARDS) was most frequently documented (28.36%), followed by acute cardiac injury 128 (7.89%) and acute kidney injury (7.60%). 129 . 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 //doi.org/10. /2020 Discussion 130 COVID-19 poses a significant burden on the healthcare system all over the world. A complete 131 understanding of the characteristics of the disease is important for effective surveillance and 132 public health response measures to be implemented in a timely manner. Currently, although we 133 have some basic understanding of the clinical and epidemiological features of COVID-19 134 patients, our knowledge is insufficient. This is because inconsistencies still exist in the findings 135 of many published reports, and the sample sizes in most of these reports were too small for a 136 reliable summary to be made. In this work, a systematic review and pooled analysis was 137 performed to combine data from 69 previous reports, in order to yield a more accurate summary 138 of the clinical and epidemiological characteristics of COVID-19 patients. 139

In many instances, susceptibility to viral infections may be related to factors such as 141 gender and smoking habits (72-74). For the former, it is believed that X chromosome 142 inactivation in females may cause cellular mosaicism which ensures the presence of at least 143 one functional copy of X-linked immune genes, thus conferring women an increased resistance 144 against viral infections (75). In addition, estrogen, the major female sex hormone, is known to 145 promote adaptive immune response (76), while testosterone, the primary sex hormone in men, 146 could contribute to the suppression of the innate immune response, rendering men more 147 susceptible to viral infections (77, 78). On the other hand, cigarette smoking may reduce the 148 level of circulating immunoglobulins, immune cells, and pro-inflammatory cytokines, as well as 149 disrupt the response of antibodies to antigens (72). For these reasons, some studies have 150 suggested that men and smokers are more susceptible to SARS-CoV-2 infections (3, 79). In the 151 present work, we noted that the ratios of male to female and smokers to non-smokers were 152 close to 1:1. Although the relative risk or odds ratio of the association between these variables 153 and SARS-CoV-2 infection could not be computed due to the lack of a comparison group, a 154

proportion of approximately 1:1 suggests that susceptibility to SARS-CoV-2 infection is universal. 155 . 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 .

The present work also showed that the symptoms of COVID-19 were generally non-157 specific, thus the disease cannot be reliably distinguished from other infectious diseases based 158 on the symptoms alone. The most commonly observed symptoms were similar to those of the 159 previous coronavirus disease outbreaks (MERS and SARS), i.e. fever, cough, and myalgia or 160 fatigue. Nevertheless, compared to MERS and SARS, the proportion of afebrile patients was 161 much higher in COVID-19 (16.79% cf. 2% in MERS and 0-1% in SARS) (80). This indicates that 162 a significant number of COVID-19 patients would be missed if surveillance and monitoring 163 systems focus largely on temperature screening, as commonly practiced in airports (81, 82). 164

The present work also showed that dyspnea was observed in only 16.97% of the patients. This 165 contradicts with advisories and guidelines published by many health authorities, which suggest 166 that dyspnea is a commonly observed symptom in . Besides, it was observed 167 that 0.80% of the patients were asymptomatic. Currently, whether asymptomatic patients can 168 transmit the virus to other individuals is not fully known, but it is highly possible (35). Thus, 169 although the number of asymptomatic patients was low, identifying and isolating such patients 170 to prevent uncontrolled disease spread would prove very challenging. It is therefore important 171 for diagnostic tests to be performed on asymptomatic medium-and high-risk individuals to 172 facilitate early detection and prevention of SARS-CoV-2 transmission. In addition to nucleic acid 173 testing using real-time reverse transcription polymerase chain reaction, some studies have 174 suggested the potential usability of chest CT for COVID-19 diagnosis (90, 91). However, in the 175 present work, we found that 5.86% of the patients did not have abnormalities on CT scans. Thus, 176 although CT findings have substantial accuracy in identifying the disease (90, 91), the results need 177 to be interpreted with caution. 178 179 SARS-CoV-2 is known to infect a cell by first binding to its angiotensin converting 180 enzyme 2 (ACE2) receptor (92). Apart from the lung, high expression of ACE2 receptor is also 181 . 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 observed in several other organs such as the heart, kidney, and intestine, as well as the in 182 lymphocytes (93, 94) . Several previous studies reported that a decreased lymphocyte count 183 was a common feature of SARS-CoV-2 infection (2, 3, 7, 30, 41) . In the present work, 184 lymphopenia was observed in 51.39% of the patients. A decreased lymphocyte count implies a 185 weakening adaptive immune system. Considering the high expression of ACE2 in lymphocytes, 186

it has been postulated that SARS-CoV-2 may directly infect and attack lymphocytes, thus 187 impairing the immune system (95). Besides the decrease in lymphocyte count, the present 188 study also showed that many COVID-19 patients had increased levels of C-reactive protein, 189 creatine kinase, lactate dehydrogenase and procalcitonin. High levels of C-reactive protein and there is a possibility that some overlapping patients were not removed from our analysis and 204 their characteristics were overreported. Besides, since patient-level data were not reported in 205 most of the studies, median values and standard deviations, which understandably provide 206 more meaningful information, could not be computed. Finally, as mentioned above, various 207 . 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/10.1101/2020.04.02.20050989 doi: medRxiv preprint comparisons among the patients (e.g. severe vs. mild, and death vs. survivor) could not be 208 analyzed due to insufficient data available. 209 210

In conclusion, this report has successfully provided a more complete picture of the clinical and 212 epidemiological characteristics of COVID-19 patients. A wide variation exists in the clinical 213 manifestation of the disease. As the outbreak continues to escalate and SARS-CoV-2 continues 214 to mutate (97), it is important to consistently update the characteristics of the patients in order to 215 monitor whether evolving strains of the virus could cause the disease differently. Sharing of 216 clinical and epidemiological data among the scientific community is highly important for 217 informing public health decision making for controlling the spread of the disease. 218

. 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 Contributor 219

SCT contributed solely to this work. 220 221

The author declares no competing interests. 223 224

No funding was obtained for this work. 226 . 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.

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multicenter study]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = 325

Chinese journal of hepatology. 2020;28 (2) . 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 . https://doi.org/10.1101/2020.04.02.20050989 doi: medRxiv preprint 494 Figure 1 : Flow chart of study selection 495 . 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 

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