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. 2022 Jul 31:10.1111/jebm.12483. Online ahead of print. doi: 10.1111/jebm.12483

Clinical manifestations of COVID‐19: An overview of 102 systematic reviews with evidence mapping

Xufei Luo 1, Meng Lv 2,3,4, Xianzhuo Zhang 5, Janne Estill 6,7, Bo Yang 8, Ruobing Lei 2,3,4, Mengjuan Ren 1, Yunlan Liu 1, Ling Wang 1, Xiao Liu 1, Qi Wang 9,10, Min Meng 2,3,4,11, Yaolong Chen 1,2,12,13,14,15,16,17,18,19,✉; the COVID‐19 evidence and recommendations working group
PMCID: PMC9353366  PMID: 35909298

Abstract

Objective

Coronavirus disease 2019 (COVID‐19) has rapidly spread worldwide, but there is so far no comprehensive analysis of all known symptoms of the disease. Our study aimed to present a comprehensive picture of the clinical symptoms of COVID‐19 using an evidence map.

Methods

We systematically searched MEDLINE via PubMed, Web of Science, Embase, and Cochrane library from their inception to March 16, 2021. We included systematic reviews reporting the clinical manifestations of COVID‐19 patients. We followed the PRISMA guidelines, and the study selection, data extraction, and quality assessment were done by two individuals independently. We assessed the methodological quality of the studies using AMSTAR. We visually presented the clinical symptoms of COVID‐19 and their prevalence.

Results

A total of 102 systematic reviews were included, of which, 68 studies (66.7%) were of high quality, 19 studies (18.6%) of medium quality, and 15 studies (14.7%) of low quality. We identified a total of 74 symptoms including 17 symptoms of the respiratory system, 21 symptoms of the neurological system, 10 symptoms of the gastrointestinal system, 16 cutaneous symptoms, and 10 ocular symptoms. The most common symptoms were fever (67 studies, ranging 16.3%–91.0%, pooled prevalence: 64.6%, 95%CI, 61.3%–67.9%), cough (68 studies, ranging 30.0%–72.2%, pooled prevalence: 53.6%, 95%CI, 52.1%–55.1%), muscle soreness (56 studies, ranging 3.0%–44.0%, pooled prevalence: 18.7%, 95%CI, 16.3%–21.3%), and fatigue (52 studies, ranging 3.3%‐58.5%, pooled prevalence: 29.4%, 95%CI, 27.5%–31.3%). The prevalence estimates for COVID‐19 symptoms were generally lower in neonates, children and adolescents, and pregnant women than in the general populations.

Conclusion

At least 74 different clinical manifestations are associated with COVID‐19. Fever, cough, muscle soreness, and fatigue are the most common, but attention should also be paid to the rare symptoms that can help in the early diagnosis of the disease.

Keywords: clinical manifestations, COVID‐19, evidence map, SARS‐CoV‐2, systematic review

1. INTRODUCTION

Human coronaviruses have in the past caused widespread outbreaks of serious diseases, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). 1 At the end of 2019, a novel coronavirus was identified as the etiology of a group of cases of pneumonia. The virus spread rapidly, resulting in an epidemic throughout China, followed by an increasing number of cases in other countries throughout the world. In February 2020, the World Health Organization (WHO) named the coronavirus disease 2019 (COVID‐19). 2 The virus that causes COVID‐19 has been given the name severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). On January 30, 2020, the WHO declared the outbreak a Public Health Emergency of International Concern (PHEIC) 3 and on 11 March 2020, a pandemic. 4 As of August 10, 2021, the reported cumulative COVID‐19 death toll surpassed four million lives, and the pace of deaths is accelerating. COVID‐19 pandemic is becoming regular in our lives. 5

Clinical symptoms are the external manifestations of the disease and are important for the diagnosis, treatment, and evaluation of the disease. Pneumonia is the most common manifestation in patients with COVID‐19, characterized primarily by fever, fatigue, dry cough, dyspnea, and other similar symptoms. 6 Some patients also exhibit gastrointestinal symptoms, such as anorexia, nausea, vomiting, and diarrhea. 7 Ocular manifestations have also been reported in some COVID‐19 patients. 8 Since the end of March 2020, skin manifestations and loss of sense of smell and taste have also been reported in patients with COVID‐19. 9 , 10 As of April 20, 2021, several systematic reviews of the symptoms of COVID‐19 have been published. 11 , 12 , 13 , 14 , 15 However, none of these have attempted to describe the full range of clinical manifestations of COVID‐19.

Evidence mapping is a method to summarize the evidence. It consists of a comprehensive search of the relevant research, systematical summarization of the basic characteristics and results of various types of studies, and an accurate visual representation of the evidence, progress, and problems in the field, to provide a comprehensive picture of research in the field and improve the effectiveness and usefulness of research in the field. 16 This study aimed to summarize the existing knowledge on clinical manifestations of COVID‐19 using evidence mapping to present a full picture of the clinical manifestations of COVID‐19 patients to provide a basis for clinical practice.

2. METHODS

2.1. Registration and reporting guideline

This study has been prospectively registered in the PROSPERO, and the registration number is CRD42021251418. We conducted this overview with an evidence mapping study following the guideline of Campbell Collaboration. 17 We used the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines for reporting of methods and findings of this study 18 (Supplementary Material 1).

2.2. Eligibility criteria and literature search

Systematic reviews were included if they met one of the following criteria: (1) systematic reviews with meta‐analyses that pooled the incidence of different clinical manifestations of COVID‐19; (2) systematic review with the proportions of different clinical manifestations of COVID‐19. If the format of Population, Intervention, Comparison, Outcomes, and Study design (PICOS) is used to present our research questions, P is for COVID‐19 patients, I and C are not applicable, and O is different clinical manifestations of COVID‐19 patients, and S is systematic review.

We excluded studies on traditional Chinese medicine; studies focusing on other diseases in patients with COVID‐19. We also excluded the systematic reviews that were not able to extract the incidence of COVID‐19 symptoms and systematic reviews that were not able to access the full text after contacting the corresponding authors by email. The definition of the systematic review was determined according to the criteria of the Cochrane Handbook.

We searched MEDLINE via PubMed, Web of Science, Embase, and Cochrane library on March 16, 2021, with the terms [“2019‐nCoV” OR “novel coronavirus” OR “COVID‐19” OR “SARS‐CoV‐2” OR “2019 novel coronavirus”] AND [“systematic review” OR “meta‐analysis” OR “literature review”] AND [“characteristics” OR “features” OR “manifestations” OR “presentation” OR “symptoms”] published between January 1, 2020 and March 16, 2021 without any language restriction (see Supplementary Material 2 for details of search strategies). We also searched Google Scholar, the WHO database of publications on COVID‐19 (https://www.who.int/emergencies/diseases/novel‐coronavirus‐2019/global‐research‐on‐novel‐coronavirus‐2019‐ncov), and the reference lists of the included studies to find reports of additional studies. All searches were conducted independently by two separate reviewers (XL and XZ), and if the number of searches was inconsistent, the two reviewers searched together and determined the results.

2.3. Study selection

Two reviewers (XL and ML) independently screened the titles, abstracts and full texts based on the inclusion and exclusion criteria. Before the screening, the two reviewers (XL and ML) performed a pretest extraction of 100 papers until an agreement on the screening process was reached. Disagreements were resolved by discussion with a third reviewer (YC). If the full text was not available, we contacted the authors to request the full text or further details. All screening was done using EndNote 20 software (Bld16742, Copyright © 1988–2021 Clarivate Analytics) except for full text.

2.4. Data extraction and quality appraisal

Two groups of two reviewers (YL and ML, MR and LW) independently extracted the data. We extracted the following basic information: (1) title, (2) first author and his/her country, (3) journal, (4) the number of included studies, (5) study design of included studies, and (6) sample size; and the following information on the results: manifestations outcomes and related statistical indicators (prevalence, effect size, 95% confidence interval (CI), I 2, P). If essential information was missing, we contacted the author to get the data, or used data conversion to the largest possible extent. Data that could not be obtained were discarded.

We assessed the methodological quality of the included systematic reviews using the “A MeaSurement Tool to Assess systematic Reviews” (AMSTAR) instrument. 19 The AMSTAR score has a total of 11 points, with studies scoring between 9 and 11 being of high quality, studies scoring between 6 and 8 of medium quality, and studies scoring between 0 and 5 of low quality. Quality assessments were done by two independent reviewers (XL and RL) and were determined by consulting a third reviewer (YC) in case of inconsistency.

2.5. Data analysis

We presented the general characteristics of the included studies descriptively. We calculated the ranges for the proportion of COVID‐19 patients having different symptoms. We presented the outcomes visually using a human anatomy diagram and a heat map. The heat map was prepared using Microsoft Excel 2016 software, and the human anatomy diagram was done using the Edraw Software (https://www.edrawsoft.com/). The clinical characteristics of COVID‐19 patients were divided into five parts according to the different systems of the body: (1) respiratory symptoms; (2) neurological symptoms; (3) gastrointestinal symptoms; (4) cutaneous symptoms, and (5) ocular symptoms. We also divided the population into three categories, namely the general population, neonates, children and adolescents, and pregnant women. The pooled prevalence estimate (PPE) will be performed for each symptom using the Comprehensive Meta‐analysis software, and if possible, we will examine the differences in prevalence by country, age, and gender.

3. RESULTS

3.1. Results of study selection

Our initial search revealed 2811 records, 759 of which were excluded as duplicates. After screening the titles and abstracts, 1897 of the remaining studies were excluded because of not related to COVID‐19. We reviewed the full texts of the remaining 155 articles and excluded 53 irrelevant articles, 38 articles that did not pool clinical symptoms, and five articles that only reported on complications. Finally, we identified 102 systematic reviews related to the clinical symptoms of COVID‐19. Figure 1 shows the flow of search and selection. Supplementary Material 3 presents a list of the inclusion and exclusion of systematic reviews.

FIGURE 1.

FIGURE 1

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Flow chart of the literature search and selection

3.2. Characteristics of the included studies

Ninety‐three (91.2%) of the 102 studies were systematic reviews with meta‐analyses, the others have calculated percentages of different kinds of symptoms but no meta‐analysis. They were published between March 11, 2020 and March 4, 2021, with 89 (87.3%) of them in 2020. One hundred and two studies were conducted mainly in 26 countries or regions, 28 (27.5%) of the studies were conducted in China; 16 (15.7%) in Iran; 8 (7.8%) in India; 7 (6.9%) in the United States; five (4.9%) in the United Kingdom; four (3.9%) each in Italy and Brazil; three (2.9%) each in Malaysia, Nigeria, and Republic of Korea; two (2.0%) each in Colombia, Nepal, Canada, Egypt, and France; and one (1.0%) each in Singapore, Indonesia, Philippines, Switzerland, Ethiopia, Turkey, Australia, Bangladesh, Peru, Kuwait, and the United Arab Emirates. Most included systematic reviews (n = 74, 72.5%) focused on the general populations of COVID‐19, 15 (14.7%) systematic reviews focused on neonates, children, and adolescents, and 13 (12.8%) were pregnant women. The number of studies included in the systematic reviews varied from 5 to 349, and the sample size included varied from 33 to 280,000 COVID‐19 patients, and the types of studies included were mainly case reports, case series, and other observational studies. Table 1 describes the characteristics of the included studies.

TABLE 1.

Characteristics of the included systematic reviews and meta‐analyses

Research ID Published/online date Country/region of First Author Patients Journal title abbreviations Number of included primary studies Number of participants Age of participants (in years; range or mean) Female
Hashan et al. 2021/3/1 Australia General populations EClinicalMedicine 49 25,567 Mean: 81.5 years NA
Shehab et al. 2021/3/4 Kuwait General populations BMJ Open Gastroenterol 158 78,798 Mean: 66.6 years 45.20%
Soltani et al. 2021/1/12 Iran General populations Rev Neurosci 14 3148 Ranged from 19 to 95 years NA
Kouhsari et al. 2020/11/4 Iran General populations Indian J Med Microbiol 50 8815 Mean: 46 years 46%
Soheili et al. 2021/2/18 Iran Pregnant women J Matern Fetal Neonatal Med 11 177 NA 100%
Irfan et al. 2021/2/16 Canada Neonates, children and adolescents Arch Dis Child 129 10,251 Mean: 7 years 44.50%
Zhong et al. 2021/2/5 China General populations Medicine 40 2459 NA 37.70%
Hassanipour et al. 2020/12/21 Iran Pregnant women Int J Reprod Biomed 10 135 Ranged from 22 to 42 years 100%
Xie et al. 2020/12/4 China General populations Ann Palliat Med 90 16,526 Ranged from 37 to 68 years 46.90%
Olumade et al. 2021/2/5 Nigeria General populations J Med Virol 7 4499 NA 31.20%
Nasiri et al. 2021/1/20 Iran General populations J Ophthalmic Vis Res 38 8219 NA 55.30%
Israfil et al. 2021/1/11 Bangladesh General populations Front Public Health 34 10,889 Mean 50.6 years 39.70%
Goel et al. 2021/1/27 India General populations Obstet Gynecol Sci 7 3231 Ranged from 47 to 62 years 44.85%
Lee et al. 2020/12/15 USA General populations Dermatol Online J 71 144 Mean: 45.9 years 46.50%
Nazari et al. 2021/1/9 Iran General populations Brain Behav 64 11,687 Mean 48.6 years 47.60%
Jafari et al. 2020/12/1 Iran Pregnant women Rev Med Virol 349 138,176 Mean age 51.2 (nonpregnant) Mean age 33 (pregnant) 100%
Khamis et al. 2020/12/3 United Arab Emirates General populations J Formos Med Assoc 35 10,972 NA NA
Islam et al. 2020/11/27 Malaysia General populations Front Neurol 86 14,275 Ranged from 35.0 ± 8.0 to 70.7 ± 13.5 years 49.40%
Merola et al. 2020/10/12 Italy General populations Acta Gastroenterol Belg 33 4434 NA NA
Saniasiaya et al. 2020/12/15 Malaysia General populations Otolaryngol Head Neck Surg 59 29,349 Ranged 28.0 ± 16.4 to 66.4 ± 14.9 years 64.40%
Ciaffi et al. 2020/10/28 Italy General populations BMC Rheumatol 88 (51 in meta) NA NA NA
Silva et al. 2020/11/25 Brasil General populations Rev Soc Bras Med Trop 43 18,246 NA NA
Wang et al. 2020/11/25 China General populations Medicine 25 4881 NA NA
Li et al. 2020/11/2 China Neonates, children and adolescents Front Pediatr 96(54 in meta) 7004 NA NA
Novoa et al. 2021/2/2 Peru Pregnant women Travel Med Infect Dis 37(4 in meta) 322 range 20−45 100%
Saniasiaya et al. 2020/12/5 Malaysia General populations Laryngoscope 83 27,492 NA NA
Karabay et al. 2020/11/19 Turkey Neonates, children and adolescents J Matern Fetal Neonatal Med 35 NA NA NA
Aggarwal et al. 2020/11/5 India General populations PLoS One 16 2347 NA NA
Alimohamadiÿ et al. 2020/10/6 Iran General populations J Prev Med Hyg 54 NA NA NA
Cagnazzo et al. 2020/10/30 France General populations J Neurol 39 68,361 Mean age 64.4 49%
Yee et al. 2020/10/22 Republic of Korea General populations Sci Rep 11 9370 NA NA
Favas et al. 2020/12/1 India General populations Neurol Sci 212(74 in meta) NA NA NA
Collantes et al. 2020/7/15 Philippines General populations Can J Neurol Sci 49 6335 NA NA
Ibekwe et al. 2020/9/11 Nigeria General populations OTO Open 32 20,451 NA NA
Amorim et al. Feb‐21 Brazil General populations J Dent Res 40 10,228 NA NA
Panda et al. 2020/9/10 India Neonates, children and adolescents J Trop Pediatr 26 3707 Range: 0–18 years NA
Allotey et al. 2020/9/1 UK Pregnant women BMJ 77 96,604 NA 100%
Ochoa et al. 2021/1/4 Colombia General populations Am J Epidemiol 97 230,398 40 (11) years 69.98%
Hasani et al. 2020/8/14 Iran General populations Biomed Res Int 30 3420 NA NA
Khalil et al. 2020/8/25 UK pregnant women EClinicalMedicine 86 NA NA 100%
Kaur et al. 2020/7/9 India General populations SN Compr Clin Med 50 6635 NA NA
Jutzeler et al. 2020/7/27 Switzerland General populations Travel Med Infect Dis 148 12,149 Median age: 47 years 47.20%
Kumar et al. Jun‐20 India General populations Indian J Gastroenterol 62 8301 48.7(16.5) 46%
Gao et al. 2020/8/3 China Pregnant women BMC Infect Dis 14 236 NA NA
Chen et al. Feb‐21 China General populations J Neurol 100 NA NA NA
Pormohammad et al. Oct‐20 Canada General populations Microb Pathog 80 61,742 NA NA
Zarifian et al. Jan‐21 Iran General populations J Med Virol 67 13,251 NA 53.30%
Abdullahi et al. 2020/6/26 Nigeria General populations Front Neurol 60 11,069 NA NA
Koh et al. 2020/6/11 Singapore General populations Front Med 29 578 NA NA
Meena et al. 2020/9/15 India Neonates, children and adolescents Indian Pediatrics 27 4857 6.4 (3.4) years 43%
Tahvildari et al. 2020/5/15 Iran General populations Front Med 80 417 Mean: 49 years NA
Grant et al. 2020/6/23 UK General populations Plos One 148 24,410 49 (11) years 45.50%
Wang et al. 2020/5/1 China Neonates, children and adolescents Ann Transl Med 49 1667 NA 42.70%
Ma et al. 2021/1/1 China Neonates, children and adolescents J Med Virol 15 486 NA 40.70%
Parasa et al. 2020/6/1 USA General populations JAMA Netw Open 29 4805 Mean 52.2 years 33.20%
Wan et al. 2020/7/1 China General populations Acad Radiol 14 1115 NA NA
Park et al. 2020/5/1 Republic of Korea General populations Clin Exp Otorhinolaryngol 9 627 NA 45.00%
Sultan et al. 2020/7/1 USA General populations Gastroenterology 57 NA NA NA
Mao et al. 2020/7/1 China General populations Lancet Gastroenterol Hepatol 35 6686 NA NA
Hu et al. 2020/6/1 China General populations J Clin Virol 21 47,344 NA 48.40%
Chang et al. 2020/5/1 Taiwan, China Neonates, children and adolescents J Formos Med Assoc 9 93 NA 48.40%
Zhu et al. 2020/10/1 China General populations J Med Virol 38 3062 NA 43.10%
Fu et al. 2020/6/1 China General populations J Infect 43 3600 Median: 41 years 43.50%
Cheung et al. 2020/7/1 HongKong, China General populations Gastroenterology 69 4875 Median: 45.1 years 42.70%
Cao et al. 2020/9/1 China General populations J Med Virol 31 46,959 Median: 46.62 years 44.40%
Morales et al. 2020/3/11 Colombia General populations Travel Med Infect Dis 58 NA NA NA
Li et al. 2020/6/1 China General populations J Med Virol 10 1994 NA 42.40%
Sun et al. 2020/6/1 China General populations J Med Virol 10 50,466 NA 48.00%
Daha et al. 2020/6/1 Nepal General populations Trop Biomed 40 2735 NA 45.20%
Elshazli et al. 2021/2/2 Egypt General populations J Med Virol 125 25,252 Mean 52.1 years 47.80%
Mansourian et al. 2021/1/9 Iran Neonates, children and adolescents Arch Pediatr 32 759 NA 47.40%
Badal et al. 2020/12/8 USA Neonates, children and adolescents J Clin Virol 20 1810 Median age 8 42.74%
Chi et al. 2021/2/1 China General populations Arch Gynecol Obstet 20 386 NA NA
Sameni et al. 2020/10/29 Iran General populations Front Med 43 2621 NA NA
Wong et al. 2020/11/13 Hong Kong, China General populations Sci Rep 76 11,028 NA NA
Han et al. 2020/11/26 China Pregnant women J Perinat Med 36 1103 NA 100%
Sheleme et al. 2020/9/10 Ethiopia General populations Infect Dis (Auckl) 30 4829 Range: 0.25–94 years 47.40%
Bennett et al. 2020/9/23 UK General populations Int J Clin Pract 45 14,358 Average age 51 years 49%
Nasiri et al. 2020/7/21 Iran General populations Front Med 34 5057 NA NA
Li et al. Mar‐21 China General populations J Med Virol 212 281,461 NA NA
Yasuhara et al. Oct‐20 USA Neonates, children and adolescents Pediatr Pulmonol 46 114 Range: 0–16 years NA
Ding et al. 2020/7/3 China Neonates, children and adolescents Front Pediatr 33 396 Range: 0–17 years 56.30%
Nepal et al. 2020/7/13 Nepal General populations Crit Care 37 NA NA NA
Matar et al. 2021/2/1 USA Pregnant women Clin Infect Dis 24 136 Range: 25–34 100%
Pinzon et al. 2020/5/29 Indonesia General populations Front Neurol 33 7559 NA NA
Mantovani et al. 2020/6/17 Italy Neonates, children and adolescents Pediatr Res 19 2855 Mean age 6.9 ± 7.0 years 49.70%
Wang et al. 2020/10/1 China General populations J Neurol 41 NA NA NA
Kim et al. 2020/11/1 Republic of Korea General populations Eur Rev Med Pharmacol Sci 16 33 Median age 66 45.50%
Makvandiet al. 2020 Iran Pregnant women Gastroenterol Hepatol Bed Bench 43 374 NA 100%
Mesquita et al. 2020/11/26 Brasil General populations Wien Klin Wochenschr 152 41,409 NA NA
Jindal et al. 2020/9/30 India General populations J Family Med Prim Care 44 458 NA NA
Mirza et al. 2020/11/3 USA Neonates, children and adolescents Int J Dermatol 86 2560 NA NA
Ibrahim et al. 2020/10/21 Egypt General populations CNS spectr 20 NA NA NA
Turan et al. Oct‐20 UK Pregnant women Int J Gynaecol Obstet 63 637 NA 100%
Zhao et al. Nov‐20 China General populations J Eur Acad Dermatol Venereol 44 507 NA NA
Matar et al. Nov‐20 France General populations J Eur Acad Dermatol Venereol 56 1020 NA NA
Tsai et al. 2020/5/19 Taiwan, China General populations Front Neurol 92 NA NA NA
Souza et al. 2020/8/1 Brazil Neonates, children and adolescents Pediatr Pulmonol 38 1124 NA 42.60%
Passarelli et al. 2020/6/1 Italy General populations Am J Dent 5 10,818 NA NA
Kasraeian et al. 2020/5/19 Iran Pregnant women J Matern Fetal Neonatal Med 9 87 Median age: 30 years 100%
Yang et al. 2020/4/30 China Pregnant women J Matern Fetal Neonatal Med 18 114 NA 100%
Yang et al. 2020/5/1 China General populations Int J Infect Dis 7 1576 Median: 49.6 years 43.50%
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References of Table 1 are listed in Supplementary Material 3.

NA, not available.

According to the AMSTAR scores, among the one hundred and two reviews included, 68 studies (66.7%) were of high quality, 19 studies (18.6%) of medium‐quality, and 15 studies (14.7%) of low quality (Supplementary Material 4). The main reasons for low quality include lack of prospective registration, failure to report on conflict of interests, and nonrepeatable data extraction and screening processes, etc.

3.3. Respiratory symptoms

Seventeen different respiratory symptoms were reported in 71 systematic reviews and meta‐analyses. Cough was reported in 40 systematic reviews in the general populations, 13 in neonates, children, and adolescents, and 15 in pregnant women; sore throat was reported in 29 systematic reviews in the general populations, 8 in neonates, children, and adolescents, and 10 in pregnant women; dyspnea was reported in 49 systematic reviews, of which, 9 related to neonates, children, and adolescents, 11 related to pregnant women, and the others were in the general populations. The remaining 14 symptoms are detailed in Figure 2A and Supplementary Material 5.

FIGURE 2.

FIGURE 2

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Human anatomy diagram of COVID‐19 manifestations. (A) Respiratory symptoms; (B) neurological symptoms; and (C) gastrointestinal symptoms

The most common symptoms of the respiratory system were cough (PPE = 53.6%, 95%CI, 52.1%−55.1%), sore throat (PPE = 12.4%, 95%CI, 9.8%−15.7%), dyspnea (PPE = 19.8%, 95%CI, 18.2%−21.6%), and expectoration (PPE = 23.4%, 95%CI, 21.6%−25.3%) (Figure 2A). Prevalence of cough was inconsistent across systematic reviews, ranging between 30.0% and 72.2%. The corresponding prevalence estimate for sore throat was 0.8%−32.0%, for dyspnea 1.0%−74.0% and for expectoration 1.5%−41.8%. The prevalence estimates for cough, sore throat, dyspnea and expectoration were lower in neonates, children and adolescents and pregnant women than in the general populations (Table 2, Supplementary Material 5 and 6).

TABLE 2.

Meta‐analyses of symptoms of COVID‐19

No. Symptoms Number of SRs Pooled prevalence LCI UCI p Value
1 Cough 68 53.60% 52.10% 55.10% 0.000
2 Fever 68 64.60% 61.30% 67.90% 0.000
3 Diarrhea 63 8.10% 7.30% 9.10% 0.000
4 Headache 58 11.10% 9.00% 13.80% 0.000
5 Muscle soreness 56 18.70% 16.30% 21.30% 0.000
6 Fatigue 52 29.40% 27.50% 31.30% 0.000
7 Dyspnea 50 19.80% 18.20% 21.60% 0.000
8 Sore throat 47 12.40% 9.80% 15.70% 0.000
9 Vomiting 42 5.50% 4.70% 6.30% 0.000
10 Nausea 37 6.70% 6.00% 7.40% 0.000
11 Expectoration 32 23.40% 21.60% 25.30% 0.000
12 Dizziness 28 7.20% 5.30% 9.70% 0.000
13 Tachypnea 26 21.20% 19.80% 22.60% 0.000
14 Abdominal pain 26 3.70% 2.80% 4.80% 0.000
15 Rhinorrhea 24 7.00% 6.10% 8.00% 0.000
16 Ageusia 23 17.40% 12.50% 23.80% 0.000
17 Anorexia 21 12.90% 10.00% 16.60% 0.000
18 Anosmia 20 18.70% 12.20% 27.40% 0.000
19 Nasal congestion 19 5.10% 3.90% 6.80% 0.000
20 Hemoptysis 18 1.80% 1.20% 2.80% 0.000
21 Chest pain 17 5.80% 4.60% 7.40% 0.000
22 Chest distress 14 12.70% 8.90% 17.90% 0.000
23 Chillness 14 10.60% 8.00% 13.90% 0.000
24 Malaise 10 12.10% 7.00% 19.90% 0.000
25 Confusion 10 6.40% 4.10% 9.90% 0.000
26 Arthralgia 8 7.50% 5.20% 10.80% 0.000
27 Rash 8 14.00% 6.80% 26.60% 0.000
28 Tachycardia 6 2.10% 1.70% 2.70% 0.000
29 Chilblains‐like 5 24.60% 12.20% 43.30% 0.010
30 Livedo 5 4.60% 3.30% 6.50% 0.000
31 Conjunctivitis 5 5.50% 2.90% 10.20% 0.000
32 Pharyngeal erythema 4 12.10% 8.00% 17.80% 0.000
33 Hypoxia 4 4.00% 0.40% 29.50% 0.007
34 Urticaria 4 16.80% 14.30% 19.70% 0.000
35 Sneeze 3 4.40% 0.50% 29.60% 0.006
36 Rigor 3 2.00% 0.10% 37.80% 0.025
37 Hypothermia 3 24.80% 8.70% 53.20% 0.079
38 Delirium 3 17.50% 15.20% 20.10% 0.000
39 Constipation 3 5.50% 5.20% 5.80% 0.000
40 Papulosquamous 3 5.80% 1.70% 18.20% 0.000
41 Erythematous 3 33.90% 21.20% 49.40% 0.043
42 Pruritic 3 41.30% 17.20% 70.30% 0.569
43 Cyanosis 3 2.00% 0.30% 11.30% 0.000
44 Conjunctival congestion 3 3.80% 0.90% 13.90% 0.000
45 Eye pain 3 6.90% 1.90% 22.60% 0.000
46 Blurred vision 3 1.20% 0.00% 26.50% 0.011
47 Wheezing 2 16.90% 15.40% 18.60% 0.000
48 Chickenpox‐like Vesicles 2 16.20% 13.50% 19.40% 0.000
49 Petechia 2 3.50% 0.90% 12.50% 0.000
50 Edematous 2 6.90% 3.70% 12.30% 0.000
51 Vesicular 2 11.80% 7.80% 17.40% 0.000
52 Dry eyes 2 14.50% 12.20% 17.20% 0.000
53 Eye itching 2 9.20% 4.80% 16.80% 0.000
54 Photophobia 2 4.80% 2.00% 11.00% 0.000
55 Chemosis 2 4.50% 3.90% 5.30% 0.000
56 Lid edema 2 1.60% 0.60% 4.20% 0.000
57 Dysphonia 1 12.40% 8.30% 18.10% 0.000
58 Belching 1 0.20% 0.10% 0.40% 0.000
59 Dysacousis 1 1.60% 0.00% 97.60% 0.301
60 Drowsiness 1 42.60% 32.70% 53.20% 0.169
61 Numbness 1 5.80% 0.20% 65.40% 0.110
62 Insomnia 1 1.80% 0.20% 12.00% 0.000
63 Syncope 1 5.60% 4.30% 7.20% 0.000
64 Back pain 1 10.00% 9.50% 10.60% 0.000
65 Otalgia 1 4.00% 1.20% 12.30% 0.000
66 Heartburn 1 3.60% 3.40% 3.80% 0.000
67 Hematemesis 1 9.10% 8.80% 9.50% 0.000
68 Melena 1 5.30% 5.00% 5.60% 0.000
69 Hematochezia 1 0.60% 0.50% 0.70% 0.000
70 Goosebumps 1 13.50% 11.70% 15.50% 0.000
71 Pustule 1 1.80% 0.20% 12.00% 0.000
72 Scales 1 7.40% 2.80% 18.10% 0.000
73 Ulcer 1 1.80% 0.20% 12.00% 0.000
74 Tearing 1 12.80% 10.80% 15.10% 0.000
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SR, systematic review; LCI, lower 95% confidence intervals; UCI, upper 95% confidence intervals.

3.4. Neurological symptoms

Eighty‐eight systematic reviews and meta‐analyses covered a total of 21 different neurological symptoms: fever (67 studies), headache (58 studies), muscle soreness (56 studies), fatigue (52 studies), dizziness (28 studies), ageusia (23 studies), anosmia (20 studies), chillness (14 studies), confusion (10 studies), malaise (10 studies), arthralgia (8 studies), delirium (3 studies), rigor (3 studies), hypothermia (3 studies), dysacousis (1 study), back pain (1 study), drowsiness (1 study), numbness (1 study), otalgia (1 study), insomnia (1 study), and syncope (1 study) (Supplementary Material 5).

Fever (PPE = 64.6%, 95%CI, 9.8%−15.7%), fatigue (PPE = 29.4%, 95%CI, 27.5%−31.3%), headache (PPE = 11.1%, 95%CI, 9.0%−13.8%), and muscle soreness (PPE = 18.7%, 95%CI, 16.3%−21.3%) were the most common (Figure 2B). Prevalence of fever was above 80% in most studies, reaching up to 91.3%; the lowest reported value, 27.6%, was in a study on pregnant women. The prevalence of fatigue ranged between 3.3% and 58.5%, headache ranged between 0.1% and 67.0%, and the prevalence of muscle soreness between 3.0% and 44.0%; the lowest reported prevalence for both conditions was among pregnant women and neonates, children and adolescents. The prevalence of the remaining symptoms is detailed in Table 2 and Supplementary Material 5 and 6.

3.5. Gastrointestinal symptoms

A total of 10 gastrointestinal symptoms were reported in 67 systematic reviews and meta‐analyses. Diarrhea was reported in 63 systematic reviews and meta‐analyses (PPE = 8.1%, 95%CI, 7.3%−9.1%), vomiting in 42, nausea in 37, anorexia in 21, abdominal pain in 26, constipation in 3 studies, and 1 each in heartburn, hematemesis, melena, and hematochezia. The prevalence of diarrhea ranged between 0.1% and 19.6% (Figure 2C). Nausea (1.2%−27.0%) and vomiting (1.2%−20.0%) occurred often together. The prevalence of gastrointestinal symptoms is generally less than 20% and does not differ from the general population in neonates, children and adolescents, or pregnant women (Table 2 and Supplementary Material 5 and 6).

3.6. Cutaneous and ocular symptoms

Thirteen systematic reviews and meta‐analyses reported 16 cutaneous symptoms (Supplementary Material 5). Rash was the most common symptom reported in nine studies, and the prevalence of cutaneous symptoms according to those reviews was generally less than 20% (Figure 3B). The symptoms of the eyes were as low in incidence as those of the cutaneous. A total of 10 ocular symptoms were reported in 8 systematic reviews and meta‐analyses (Figure 3A). The ocular symptoms were relatively rare in neonates, children and adolescents, and pregnant women, and the overall prevalence was low, between 5% and 20% (Table 2 and Supplementary Material 5).

FIGURE 3.

FIGURE 3

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Human anatomy diagram of COVID‐19 manifestations. (A) Ocular symptoms and (B) cutaneous symptoms

4. DISCUSSION

4.1. Principal findings

Our study identified 74 different clinical manifestations of COVID‐19 in 102 systematic reviews and meta‐analyses. The most common respiratory symptoms were cough, sore throat, dyspnea, and expectoration, and the most common symptoms of neurological symptoms were fever, fatigue, headache, and muscle soreness. The gastrointestinal system included diarrhea, nausea, and vomiting, and we also identified some other symptoms such as manifestations of the eyes or skin. The prevalence of the same condition tended to vary broadly across the different systematic reviews and population groups, and lower prevalence of symptoms in pregnant women and neonates, children and adolescents than in the general population.

Clinical symptoms are important for the diagnosis of a disease. There is no doubt that fever, cough, and fatigue are the three most prevalent symptoms of COVID‐19 patients. Many studies have estimated the prevalence of different symptoms of SARS‐CoV‐2 infection. Like in the case of SARS‐CoV and MERS‐CoV, cough and fever are the most common symptoms, which can be caused also by many other causes, such as common flu. 20 , 21 An accurate diagnosis of COVID‐19 therefore often requires a combination of clinical symptoms, laboratory tests and CT findings. Attention in the diagnosis should also be paid to the differentiation of clinical manifestations associated with comorbidities, such as hypertension, diabetes, and coronary heart disease.

The clinical symptoms of COVID‐19 vary across population groups. One systematic review 22 suggested that children appear to have a less severe course and better prognosis than adults, and deaths in children are extremely rare. In addition, the multisystem inflammatory syndrome in children (MIS‐C) should be given more attention when diagnosing children with COVID‐19, in addition to symptoms similar to those of adults. 23 Studies have shown that pregnant women's symptoms are essentially the same as in the general population, but the prevalence was lower. 24 , 25 At the same time, gastrointestinal symptoms, eye symptoms and skin symptoms are relatively less common in pregnant women. 26

The diagnosis of SARS‐CoV‐2 infection in asymptomatic patients requires special attention. Many asymptomatic patients have been reported worldwide. Nishiura et al. 27 estimated the proportion of asymptomatic patients was 30.8% (95% CI, 7.7%−53.8%). Hu et al. found that the course of illness was milder in asymptomatic cases than in other cases. 28 However, the asymptomatic carriers may be a challenge to containment for COVID‐19 transmission. 29 Asymptomatic people can transmit SARS‐CoV‐2 to others for a long time, perhaps more than 14 days. 30 Therefore, it is important to screen asymptomatic SARS‐CoV‐2 carrier populations, when resources are available, to minimize the chance of infection, although it may raise the treatment cost31.

Our study identified some unusual symptoms, such as skin (livedo, cyanosis, edematous, etc.) and eye manifestations (conjunctivitis, blurred vision, eye pain, etc.). However, because such symptoms were rarely reported during the pre‐epidemic period, they can be easily overlooked. Patients with unusual symptoms are not easily screened and diagnosed; therefore, understanding and knowing these unusual symptoms, has important implications for the current improvement in the identification of SARS‐CoV‐2 infections. Besides, as the epidemic grows and some COVID‐19 variant strains emerge, some specific symptoms may appear. However, there is no relevant systematic review yet, and further updating of associated symptoms regarding COVID‐19 variant strains is needed in the future.

4.2. Implications for future research and practice

As the second wave of the outbreak rages on, countries need again to pay attention to finding as many infected patients as early as possible to cut the transmission chains and avoid a new wave of the epidemic. This means that even rare symptoms can be important in the screen and diagnosis. Our study found that many systematic reviews and meta‐analyses of different quality are being conducted for the same symptom, which may result in wasting research on COVID‐19, 32 and before conducting systematic reviews of symptoms for researchers, we recommend retrieval to determine if a systematic review is already available on the PROSPERO website, and if not, it should be registered.

For patients with COVID‐19 in the second wave of the epidemic, our study can provide a full picture of the symptoms map of COVID‐19 to inform the screening and diagnosis of patients. Furthermore, in the context of a global COVID‐19 epidemic, our study could help clinicians or stakeholders to identify COVID‐19 through some rare symptoms.

4.3. Strengths and limitations

To the best of our knowledge, this is the first evidence map to comprehensively review and summarize the clinical symptoms of COVID‐19. We systematically searched the main databases and performed a detailed analysis of the included literature. However, this study also has some limitations. First, because of the substantial overlap between the studies included in the systematic reviews, we have limited confidence in the pooled results of the meta‐analyses. Second, although we systematically searched the literature, there is a possibility that some studies were missed due to the constantly increasing number of COVID‐19 studies. Third, given that the frequency of COVID‐19 symptoms may be varied in different countries or territories due to different sources or genotypes of COVID‐19, we did not perform a subgroup analysis of symptoms in different geographical locations. However, this can provide information for tracing the origin of the SARS‐CoV‐2 virus. To address the above limitations, we believe it is meaningful and necessary to conduct a living systematic review of the symptoms of COVID‐19 patients.

4.4. Conclusion

In conclusion, COVID‐19 is associated with at least 74 different clinical manifestations, the most common of which are fever, cough, muscle soreness, and fatigue. In addition, some symptoms, despite being rare, may be useful in the early diagnosis of COVID‐19 in patients who otherwise have no or only mild symptoms. Future research should pay particular attention to these rare symptoms to help treat the infected patients and control the epidemic.

CONFLICT OF INTEREST

There are no relevant financial or nonfinancial competing interests to report.

Supporting information

Supplementary Material 1 PRISMA checklist

Click here for additional data file. (32.3KB, DOCX)

Supplementary Material 2 Search Strategy

Click here for additional data file. (21.3KB, DOCX)

Supplementary Material 3 Systematic Reviews and Meta‐analyses included and excluded references of this study

Click here for additional data file. (40.2KB, DOCX)

Supplementary Material 4 AMSTAR scores and main conclusions of systematic reviews

Click here for additional data file. (31.7KB, docx)

Supplementary Material 5 Heat map for different symptoms of COVID‐19

Click here for additional data file. (86.8KB, docx)

Supplementary Material 6 Subgroup analyses

Click here for additional data file. (4.4MB, docx)

ACKNOWLEDGMENTS

We thank Xianzhuo Zhang for helping to make the human anatomy diagram.

Luo X, Lv M, Zhang X, et al. Clinical manifestations of COVID‐19: An overview of 102 systematic reviews with evidence mapping. J Evid Based Med. 2022;1‐15. 10.1111/jebm.12483

Xufei Luo and Meng Lv contributed equally to the work.

REFERENCES

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Material 1 PRISMA checklist

Click here for additional data file. (32.3KB, DOCX)

Supplementary Material 2 Search Strategy

Click here for additional data file. (21.3KB, DOCX)

Supplementary Material 3 Systematic Reviews and Meta‐analyses included and excluded references of this study

Click here for additional data file. (40.2KB, DOCX)

Supplementary Material 4 AMSTAR scores and main conclusions of systematic reviews

Click here for additional data file. (31.7KB, docx)

Supplementary Material 5 Heat map for different symptoms of COVID‐19

Click here for additional data file. (86.8KB, docx)

Supplementary Material 6 Subgroup analyses

Click here for additional data file. (4.4MB, docx)

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