Coronavirus disease 2019 (COVID-19) is now a global pandemic caused by a novel coronavirus. The first case of COVID-19 was reported in December 2019 in Wuhan, China. Since then, it has affected over 138,010,168 people and caused over 2,970,000 deaths across the world [1]. Similar to other coronaviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the pulmonary system. However, multi-system involvement, including cardiac, vascular, and neurological complications, has been reported [2]. The clinical manifestations range from asymptomatic infection or mild disease with fever, myalgias, and cough to severe disease characterized by shortness of breath, hypoxemia, acute respiratory distress syndrome requiring mechanical ventilation, multi-organ failure, and death [3]. However, due to this disease’s novelty, within the first year of the initial description, the prevalence of various symptoms and comorbidities associated with the disease remains unclear.

Several studies have evaluated the prevalence of various symptoms. A systematic review of 3600 patients reported fever, cough, and fatigue as most common [4]. Similarly, another meta-analysis of 78 studies found the prevalence of gastrointestinal symptoms to be 1 out of every 5 COVID-19 patients [5]. Another systematic review described the prevalence of acute myocardial injury in COVID-19 infection and found a pooled prevalence of nearly 20% [6]. Given the variable presentations and unclear prevalence of comorbidities and the accrual of interim experience, we performed a systematic review to assess the contemporary prevalence of comorbidities and symptoms from all the published studies.

Material and methods

We performed a systematic review following the Cochrane Handbook for Systematic Reviews and Intervention statement in health care interventions [7].

Selection criteria

We included observational studies, case series (retrospective, prospective, descriptive), randomized controlled trials, and survey studies that included adults’ comorbidities or symptoms with confirmed COVID-19 infection. Individual case reports and case series with < 5 patients were excluded.

Data Sources and Search Strategy

A comprehensive literature search was done on Ovid MEDLINE(R) and Epub Ahead of Print, In-Process; Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from March 2019 to June 18, 2020. The main keywords used in the search were: (Corona virinae or corona virus or Coronavirinae or coronavirus or COVID or nCoV or 2019; or novel or new) or (Corona virinae or & corona virus; or Coronavirinae or coronavirus or COVID or nCoV) and wuhan) or Corona virinae19; or ;Corona virinae 2019 or &quot;corona virus19 or &;corona virus2019; or Coronavirinae19 or Coronavirinae2019 or coronavirus19 or coronavirus2019 or COVID19 or COVID2019 or nCOV19 or nCOV2019 or;2019-nCOV or 2019nCOV or SARS Corona virus or SARS Coronavirus or SARS-COV-2. Two investigators (D.R. and R.P.) reviewed the titles and abstracts of the identified studies independently and screened them as per the selection criteria mentioned above. Any conflict was resolved with the consensus of a third investigator (R.T.).

Data abstraction

Data from included studies were independently abstracted by two investigators (D.R. and M.W.T.). The abstracted data included study design and setting, month and year of publication, duration of the study period, gender, comorbidities, symptoms and severity, mortality, survival, and discharge data. Data extraction excluded studies with pediatric patients. All comorbidities were initially abstracted separately, then grouped based on system involvement for data analysis. Similarly, all symptoms were extracted separately, then subsequently grouped for analysis.

Statistical analysis

The frequency of variable occurrence was calculated using percentages. For comorbidity analysis, studies with fewer than 3 reported comorbidities were excluded. Primary analysis involved the calculation of the presence of comorbidities and symptoms in the pooled data. Comorbidities and symptoms were compared based on the severity of the patients studied. For this stratification, we included studies reporting symptoms or comorbidities exclusively for severe or non-severe cases. Studies with severe and non-severe cases with inseparable comorbidity or severity data were excluded. A χ2 test was performed with α set at 0.05. All analyses were performed using SPSS version 25.


The preliminary database search resulted in 4032 studies; 24 other studies were identified from other sources; after the titles’ preliminary screening, 233 full-text studies were reviewed. Of these, 163 studies were included in the systematic reviews and in the primary analysis of symptoms [8170]. For comorbidity analysis, 41 of 163 studies were excluded based on fewer than three reported comorbidities criteria, as described above, yielding 122 studies. A flow chart of the study selection is shown in Figure 1. The details of the included studies are provided in Table I.

Figure 1

Flow chart low study
Table I

Baseline characteristics of included studies

Author name, yearStudy periodType of studyPatients NFemale patients (N)Hospitalization statusSeverity
Akalin et al., 2020Mar 16–Apr 1Retrospective single-center case series36103B
An Ping et al., 2020Jan 17–Jan 24Retrospective single-center case series951
Bangalore et al., 2020Retrospective single-center case series183
Beigel JH et al., 2020Feb 21–Apr 19RCT double blinded10633771B
Bhatraju PK et al., 2020Feb 24–Mar 9Retrospective multi-center case series2491S
Borba MGS et al., 2020Mar 23–Apr 5Parallel, double-masked, randomized, phase IIb clinical trial81201S
Cai Qingxian et al., 2020Jan 30–Feb 14Open labelled non-randomized control study80451B
Cai Qingxian et al., 2020Jan 11–Feb 6Retrospective single-center case series2981531B
Cao Jianlei et al., 2020Jan 3–Feb 1Retrospective single-center case series102491B
Chan Fuk-Woo J et al., 2020Retrospective single-center case series631
Chang De et al., 2020Jan 16–Jan 29Retrospective multi-center case series1331
Chen J et al., 2020Jan 20–Feb 7Retrospective single-center case series2491231B
Chen L et al., 2020Dec 8–Mar 20Retrospective multi-center case series118B
Chen Nanshan et al., 2020Jan 1–Jan 20Retrospective single-center case series99321B
Chen Qing et al., 2020Retrospective single-center case series941NS
Chen Qingqing et al., 2020Jan 1–Mar 11Retrospective multi-center case series145661B
Chen Tao et al., 2020Jan 13–Feb 12Retrospective single-center case series274103S
Chen TL et al., 2020Jan 1–Feb 10Retrospective single-center case series20395B
Cholankeril George et al., 2020Mar 4–Mar 24Retrospective single-center case series116541B
Chu J et al., 2020Jan 7–Feb 11Retrospective single-center case series54181B
COVID-19 National Emergency Response Center, Epidemiology and Case Management Team, Korea Centers for Disease Control and PreventionBefore 2/14/2020Retrospective multi-center case series28133B
COVID-19 National Incident Room Surveillance TeamRetrospective single-center case series2953B
Dai H et al., 2020Jan 10–Feb 7Retrospective multi-center case series23498
Deng Qing et al., 2020Jan 6–Feb 20Retrospective single-center case series112551B
Dong X et al., 2020Retrospective multi-center case series1161
Du Rong-Hui et al., 2020Dec 25–Feb 7Prospective single center cohort179821B
Du Y et al., 2020Jan 9–Feb 15Retrospective single-center case series85231S
Escalera-Antezana JP et al., 2020Mar 2–Mar 15Retrospective multi-center case series1262NS
Hua Fan et al., 2020Dec 30–Feb 16Retrospective single-center case series101371S
Fei Xiao et al., 2020Feb 1–Feb 14Retrospective single-center case series73321B
Feng Pan et al., 2020Jan 12–Feb 6Retrospective single-center case series21151NS
Feng Yun et al., 2020Jan 1–Feb 15Retrospective multi-center case series4762051B
Fernández-Ruiz Mario et al., 2020March 5–March 23Retrospective single-center case series1841B
Gautret Philippe et al., 2020Feb–MarchProspective single center cohort80371B
Geleris et al., 2020Mar 7–Apr 8Cross-sectional Multi-center case series13765951B
Giacomelli A et al., 2020Cross-sectional single-center case series59191
Goyal et al., 2020Mar 3–mar 27Retrospective single-center case series3931551B
Griiti Giuseppe et al., 2020Retrospective single-center cohort2131B
Guan W et al., 2020Dec 11–Jan 29Retrospective multi-center case series10994593B
Guo Tao et al., 2020Jan 23–Feb 25Retrospective single-center case series187961B
Hajifathalian K et al., 2020Mar 4–Apt 9Retrospective multi-center case series10594483B
Han Chaoqun et al., 2020Feb 13–Feb 29Retrospective single-center case series2061151NS
Hong Kyung Soo et al., 2020Mar–20Retrospective single-center case series98601B
Horby P et al., 2020Early 2020–June 8Randomized controlled open labelled trial642523371B
Huang Chaolin et al., 2020Dec 16–Jan 2Prospective single center cohort41111B
Huang Yihui et al., 2020Dec–JanRetrospective single-center case series34143B
Israelsen S B et al., 2020Mar 10–April 23Retrospective single-center case series175901B
Javanian M, et al. 2020Feb 25–Mar 12Retrospective multi-center case series110491
Jin Xi et al., 2020Jan 17–Feb 8Retrospective multi-center case series6513201B
Kaye et al., 2020Mar 25–Apr 3Retrospective multi-center case series237129
Kim ES et al., 2020 (Korea National Committee for Clinical Management of COVID-19 (KNCCMC))FebProspective multi-center case series28131B
Klopfenstein T et al., 2020Mar 1–Mar 17Retrospective single-center case series1141B
Kluytmans-van den Bergh M et al., 2020Mar 7–Mar 12Cross-sectional multi-center case series86713NS
Kuang Y et al., 2020Jan 1–Feb 10Retrospective multi-center cohort944476B
Kujawski Stephanie et al., 2020Jan 20–Feb 5Retrospective multi-center case series1243B
Lechien JR et al., 2020Retrospective multi-center case series4172631NS
Lei H et al., 2020Jan 25–Jan 27Retrospective multi-center case series821
Lei S et al., 2020Jan 1–Feb 5Retrospective multi-center case series34201B
Lei Wang et al., 2020Jan 21–Feb 5Retrospective single-center case series1881
Lei Z et al., 2020Jan 22–Feb 12Retrospective single-center case series2010
Li Kunhua et al., 2020Jan–FebRetrospective multi-center case series83391B
Li X et al., 2020Jan 14–Feb 13Retrospective single-center case series25151S
Li Xiaochen et al., 2020Jan 26–Feb 5Retrospective single-center cohort5482691B
Lian J et al., 2020Jan 17–Jan 31Retrospective single-center case series465222B
Lian J et al., 2020Jan 17–Feb 12Retrospective multi-center case series788381
Liang WH, et al., 2020Nov 21–Jan 31Retrospective multi-center case series1590674B
Lin Lu et al., 2020Jan 17–Feb 15Retrospective single-center case series95501B
Liu Jui-Yao et al., 2020Jan 21–Apr 6Retrospective multi-center case series321170NS
Liu Kai et al., 2020Jan 15–Feb 18Retrospective single-center case series56251B
Liu Kiu et al., 2020Dec 30 –Jan 24Retrospective multi-center case series137761B
Liu Yingxia et al., 2020December 26–JanuaryRetrospective single-center case series1241B
Liu Zhe et al., 2020Jan 16–Feb 13Retrospective multi-center case series72331B
Lo LI et al., 2020Jan 21–Feb 16Prospective single center case series1071B
Luo Shihua et al., 2020Jan 1–Feb 20Retrospective single-center case series183811B
Lu-Xiaofan et al., 2020Jan 25–Feb 25Retrospective single-center case series2441161S
Ma J et al., 2020Jan 1–Mar 30Retrospective single-center case series37201B
Mahevas M et al., 2020Mar 12–Mar 31Retrospective multi-center case series1731011B
Mathian A et al., 2020Mar 29–Apr 6Cross-sectional single-center case series17133B
Meng Yifan et al., 2020Jan 16–Feb 4Retrospective single-center case series168821S
Mi Bobib et al., 2020Jan 1–Feb 27Retrospective multi-center case series1081B
Million M et al., 2020Mar 3–Mar 31Retrospective multi-center cohort10615693B
Mo P et al., 2020Jan 1 –Feb 5Retrospective single-center case series155691B
Moein S et al., 2020Mar 21–Apr 5Prospective single center case series60201B
Morena V et al., 2020Mar 10–Mar 23Prospective single center open label study5111S
Nobel Yael et al., 2020Mar 10–Mar 21Retrospective single-center cohort278133B
Pan Lei et al., 2020Jan 18–Feb 28Cross-sectional multicenter case series103481B
Pung Rachel et al., 2020Jan–FebRetrospective multi-center case series17102NS
Qi X et al., 2020Jan 23–Feb 18Retrospective multi-center case series701B
Qian GQ et al., 2020Jan 20–Feb 11Retrospective multi-center case series91541B
Redd WD et al., 2020Feb 11–Feb 29Randomized, parallel, open label trial150681B
Richardson Safiya et al., 2020Before April 2Retrospective multicenter cohort3181441B
Rodríguez-Cola M et al., 2020Mar 1–Apr 4Retrospective multi-center case series570022631B
Ronald LT et al., 2020Mar 20 –Apr 4Prospective single center case series721B
Rosenberg ES et al., 2020Mar 31–Apr 10Electronic survey14594
Sciascia S et al., 2020Mar 15–Mar 28Retrospective multi-center cohort14385801B
Shaobo Shi et al., 2020Double-blind, placebo-controlled, multicenter trial6371S
Shi Heshui et al., 2020Jan 1–Feb 23Retrospective single-center case series6713491B
Shi Shaobo et al., 2020Dec 20–Jan 23Retrospective single-center case series81391NS
Shu Lei et al., 2020Jan 20–Feb 10Retrospective single-center case series4162111B
Song F et al., 2020Feb 13–Feb 29Retrospective single-center case series5452811NS
Spiteri Gianfranco 2020Jan 20–Jan 27Retrospective single-center case series51261NS
Tabata Sakiko et al., 2020Jan 24 –Feb 21Retrospective multi-center case series38133NS
Tang Wei et al., 2020Feb 11–Feb 25Retrospective single-center case series104501B
Tian S et al., 2020Jan 20–Feb 10Retrospective multi-center case series262135B
Toniati Paola et al., 2020Mar 9–Mar 20Multicenter prospective non-randomized study100121S
Tu Wen-Jun et al. 2020Jan 3–Feb 24Retrospective single-center case series174951B
Wan S et al., 2020Jan 23–Feb 8Retrospective single-center case series135633
Wan Yunle et al., 2020Jan 19–Mar 6Retrospective multi-center case series2321011B
Wang Dawei et al., 2020Jan 1–Jan 28Retrospective single-center case series138631B
Wang J et al., 2020Jan–FebProspective multicenter case series9336
Wang L et al., 2020Jan 1–Feb 6Retrospective single-center case series3391731B
Wang Lizhen et al., 2020Jan 31–Feb 12Retrospective single-center case series26151
Wang Luwen et al., 2020Jan 14–Feb 13Prospective single center cohort116491B
Wang Min et al., 2020Jan 21–Feb 2Retrospective multi-center case series66231
Wang Ruirui et al., 2020Jan 20–Feb 9Retrospective single-center case series125711B
Yang Wenjie et al., 2020Jan 17–Feb 10Retrospective multi-center cohort149681NS
Wang X et al., 2020Feb 7–Feb 12Retrospective single-center case series10124881NS
Wang X et al., 2020Jan 10–Feb 24Retrospective multi-center case series80491
Wang Yang et al., 2020Jan 25–Feb 25Retrospective single-center case series3441651S
Wang Yanrong et al., 2020Jan 11–Fbe 29Retrospective single-center case series55221NS
Wang Yeming et al., 2020Feb 6–Mar 12Randomized, double-blind, placebo-controlled, multicenter trial236961B
Wang Z et al., 2020Jan 16–Jan 29Retrospective single-center case series691
Wei XS et al., 2020Jan 19–Feb 7Retrospective single-center case series84561
Wei Jia-Fu et al., 2020Jan 16–Mar 10Prospective multicenter cohort101471B
Wentao Ni et al., 2020Retrospective single-center case series1791B
Wolfel Roman et al., 2020Jan 23–Jan 26Retrospective single-center case series91NS
Wu Chaomin et al., 2020Dec 25–Jan 26Retrospective single-center case series20173S
Wu J et al., 2020Jan 22–Feb 14Retrospective multi-center case series80411B
Wu Jiong et al., 2020Jan –FebRetrospective multi-center case series80381B
Wu Yongjian et al., 2020Jan 16–Mar 15Prospective single center case series74351B
Xia Xiao-ying et al., 2020Jan 23–Feb 18Retrospective single-center case series1041B
Xie Hansheng et al., 2020Feb 2–Feb 23Retrospective single-center case series79351NS
Xiong Fei et al., 2020Jan 1–Mar 10Retrospective multi-center cohort131561B
Xiong Ying et al., 2020Jan 11–Feb 5Retrospective single-center case series42171B
Xu T et al., 2020Jan 23–Feb 18Retrospective single-center case series51261
Xu Xi et al., 2020Jan 23–Feb 4Retrospective single-center case series90511B
Xu Xiaoling et al., 2020Feb 5–Feb 14Prospective single center case series2131S
Xu XW et al., 2020Jan 10–Jan 26Retrospective single-center case series62271NS
Xun Ding 2020Feb–MarchRetrospective single-center case series11261
Yan CH et al., 2020Mar 3–mar 29Cross-sectional single-center case series59293
Yan Yongli et al., 2020Jan 10–Feb 24Retrospective single-center case series193791S
Yang Fan et al., 2020Jan 1 –April15Retrospective single-center case series52241B
Yang X 2020Dec 24–Jan 26Retrospective single-center case series52171S
Young BE el al., 2020Jan 23–Feb 3Retrospective multi-center case series1891NS
Yu Yuan et al., 202027–FebProspective multicenter case series226871S
Zha Lei et al., 2020Jan 24–Feb 24Retrospective multi-center case series31111NS
Zhang Guqin et al., 2020Jan 2–Feb 10Retrospective multi-center case series2211131B
Zhang JingCheng et al., 2020Jan 27–Feb 10Retrospective single-center case series1471NS
Zhang Jin-Jin et al., 2020Jan 16–Feb 3Retrospective single-center case series140691B
Zhang Jun et al., 2020Jan 28–Feb 24Retrospective single-center case series131B
Zhang L et al., 2020Jan 13–Feb 26Retrospective multi-center case series28111B
Zhang Xiaoli et al., 2020Jan 17–Feb 8Retrospective multi-center case series6453171B
Zhao Xin-Ying et al., 2020Jan 16–Feb 10Retrospective single-center case series91421B
Zhao D et al., 2020Jan 23–Feb 5Retrospective multi-center case series1981
Zhao Wei et al., 2020Retrospective single-center case series101451
Zheng F et al., 2020Jan 17–Feb 7Retrospective single-center case series161811B
Zheng Y et al., 2020Jan 16–Feb 20Retrospective single-center case series99481B
Zhou Fei et al., 2020Dec 29–Jan 31Retrospective multi-center cohort1911191S
Zhou Shuchang et al., 2020Jan 16–Feb 12Retrospective single-center case series100461NS
Zhou Shuchang et al., 2020Jan 16–Jan 30Retrospective single-center case series62231B
Zhou Y et al., 2020Jan 28–Mar 2Prospective single center case series2181S
Zhou Zili et al., 2020Dec 20–Feb 9Retrospective single-center case series2541391
Zou Lirong et al., 2020Jan 7–Jan 26Retrospective single-center case series189

[i] Hospitalization: 1: inpatient, 2: outpatient, 3: combined inpatient, and outpatient. S – severe, NS – non-severe, B – Both, N – number, RCT – randomized controlled trial, COVID-19: coronavirus disease 2019.

Study characteristics

A total of 163 studies with 43,187 patients were included. Of these, 117 were from China, 19 from the European region, 14 from the US, 2 from other countries, and the remaining 11 were from Australia, Brazil, Iran, Japan, S Korea, Singapore, and Taiwan. The earliest study recruitment started on December 11, 2019 and ended on April 19, 2020. There were 80 retrospective single-center case series; 43 retrospective multicenter case series, 7 retrospective multicenter cohorts, 3 retrospective single-center cohorts, 6 prospective single-center series, 3 prospective single-center series, 4 prospective single-center cohort studies, 1 prospective multicenter cohort study, 7 randomized controlled trials of various design, 1 open-label non-randomized control study, 1 descriptive case series, and 1 prospective single-center open-label study (Table I). A total of 128 studies included only hospitalized patients, 13 included both hospitalized and non-hospitalized patients, 2 included only non-hospitalized patients, and 20 studies did not list hospitalization status.

Patient baseline characteristics and outcomes

For a total of 40,632 patients, the mean age was 54.6 years, with a range of 18–98 years. A total of 8 studies, including adult patients with 2,325 patients, did not provide age data. Data regarding gender were not available in 8 studies. There were significantly fewer women in the study (43.9% vs. 56.1%, p < 0.0001). Hospitalization outcomes were reported in 116 studies for 37,349 patients; 48.5% (28,779) were discharged, 29% (18,810) remained in the hospital, and 12.1% (4284) died at the end of the study period for these studies. The details regarding invasive mechanical ventilation (IMV) were reported in 61 studies with 30,190 patients, of whom 9.89% (3,359) underwent IMV.

Comorbidities and symptoms for all patients

Prevalent cardiovascular comorbidities were hypertension (31.9%), obesity (27.9%), hyperlipidemia (26.4%), smoking (18.9%), diabetes mellitus (17.2%), atherosclerotic disease (9.2%) and arrhythmia (5.0%). Asthma (7.8%), followed by chronic obstructive lung disease (COPD) or chronic lung disease (CLD) (6.2%), were the most common respiratory comorbidities. The gastrointestinal comorbidities of hepatitis, liver disease and fatty liver disease had a prevalence of 2.4%. Chronic kidney disease and/or end-stage renal disease were reported in 6.2% of patients. Cerebrovascular disease or cerebrovascular accidents were reported in 3.5% of patients. Cancer and/or malignancy were reported in 4.4%, and HIV and/or immunodeficiency were observed in 1.6% of patients.

The most often reported constitutional symptoms of COVID-19 were fever (73.9%), fatigue (33.4%), malaise (29.9%), myalgia and/or arthralgia (19.2%), generalized weakness (19.0%), and chills (11.3%). For the cardiovascular system, chest pain and/or tightness were most often reported (19.6%), followed by palpitations (5.2%). Cough (60.3%), sputum production (29.7%), shortness of breath (27.3%), loss of smell and/or taste (25.1%), rhinorrhea (12.9%), and sore throat (12.3%) were the most often reported respiratory symptoms. The most common gastrointestinal symptoms were anorexia or loss of appetite (29.4%), followed by diarrhea (14.8%), nausea and/or vomiting (13.2%), and abdominal pain (7.4%). Commonly reported neurological symptoms were headache (12.8%), confusion (9.4%), and dizziness (8.2%). The details of the prevalence of constitutional, cardiovascular, respiratory, and gastrointestinal symptoms, and their related comorbidities, along with the number of studies, are shown in Tables II and III, respectively.

Table II

Symptoms based on systems involved overall in patients with coronavirus disease 2019

Symptom%AgeNumber of patients (N)Total patientsNumber of studies
 Generalized weakness19.0043422869
Respiratory/upper respiratory infection:
 Sore throat12.3018771530278
 Sputum production29.7037891273064
 Nasal congestion6.60507765819
 Loss of smell or taste25.10740295213
 Conjunctival congestion0.902629274
 Chest pain/tightness19.601251639447
 Abdominal pain7.40504678334
Table III

Prevalence of comorbidities overall in patients with coronavirus disease 2019

 Diabetes mellitus17.20512229796107
 Atherosclerotic disease9.20264228806102
 Heart failure5.9055494039
 Hepatitis/liver disease/fatty liver2.404591931060
 CVA/cerebrovascular disease3.50320915240

[i] COPD – chronic obstructive pulmonary disease, CLD – chronic lung disease, CKD – chronic kidney disease, ESRD – end-stage renal disease, CVA – cerebrovascular accident, HIV – human immunodeficiency virus.

Subgroup analysis by severity

For stratification based on severity for comorbidities and symptoms, only 30 studies met the inclusion criteria, with a total of 5,819 cases. Table IV shows the prevalence of comorbidities and symptoms in both groups.

Table IV

Comorbidities and symptoms by severity vs. non-severity in patients with coronavirus disease 2019

ParameterNon- severeSevereP-value
 Hypertension8.1%45.2%< 0.001
 Diabetes mellitus3.5%19.5%< 0.001
 Atherosclerotic disease5.2%10.9%< 0.001
 Smoking13.5%3.8%< 0.001
 Heart failure0.0%5.2%
 Liver disease2.8%3.0%0.814
 CKD/ESRD0.8%8.7%< 0.001
 Fever58.5%87.8%< 0.001
 Myalgia/Arthralgia25.8%19.0%< 0.001
 Shortness of breath20.6%47.4%< 0.001
 Sore throat12.6%14.0%0.279
 Sputum production26.5%35.4%< 0.001
 Nasal congestion4.8%4.8%0.998
 Rhinorrhea7.3%32.2%< 0.001
 Loss of smell/taste71.5%18.6%< 0.001
 Chest pain/tightness19.3%21.1%0.34
 Abdominal pain10.3%4.2%< 0.001
 Anorexia41.0%27.1%< 0.001
 Headache20.4%10.6%< 0.001

[i] COPD – chronic obstructive pulmonary disease, CLD – chronic lung disease, CKD – chronic kidney disease, ESRD – end-stage renal disease.


Hypertension was the most commonly observed comorbidity among severe cases (45.2% vs. 8.1%, p < 0.001). Diabetes mellitus was also more common in severe disease (19.5% vs. 3.5%, p < 0.001). Obesity and congestive heart failure (CHF) were not observed in any non-severe cases among the studies included for this analysis but were present in severe cases (30.5% and 5.2%, respectively). Smoking was more commonly observed in non-severe cases than severe cases (13.5% vs. 3.8%, p < 0.001). COPD was similar in non-severe and severe cases (9.2% vs. 12.0%, p = 0.083).


Among all the symptoms compared, non-respiratory symptoms were more commonly observed among non-severe cases (headaches, anorexia, abdominal pain, loss of smell/taste). Severe compared to non-severe cases more frequently had fever (87.8% vs. 58.5%, p < 0.001), shortness of breath (47.4% vs. 20.6%, p < 0.001), cough (66.8% vs. 62.9%, p < 0.001), sputum production (35.4% vs. 26.5%, p < 0.001) and rhinorrhea (32.2% vs. 7.3%, p < 0.001). Both groups had a similar prevalence of chest pain (21.1% severe vs. 19.3% non-severe, p = 0.34), diarrhea (20.2% severe vs. 19.4% non-severe, p = 0.515), and nausea/vomiting (8.8% severe vs. 8.4% non-severe, p = 0.643).


Since the emergence of SARS-CoV-2 infection in China and its spread worldwide, the knowledge regarding disease course, clinical characteristics, and treatment options has continued to evolve. We performed a comprehensive systematic review of published studies with COVID-19 patients. This systematic review summarized the prevalence of clinical symptoms and comorbidities in COVID-19 patients, stratified by the severity of symptoms [164170].

This analysis found that the prevalence of COVID-19 was higher in men compared to women. Hypertension, obesity, hyperlipidemia, smoking, diabetes mellitus, and atherosclerotic diseases are the most common comorbidities overall. Fever, cough, fatigue, malaise, sputum production, shortness of breath, and anosmia are the most common symptoms overall. After stratification of patients on the basis of severity, hypertension, diabetes, obesity, and CHF were the most common comorbidities in severe illness. In contrast, smoking is more common in non-severe illnesses. Fever, shortness of breath, cough, sputum production, and rhinorrhea are more commonly reported in patients with severe illness, whereas headache, anorexia, abdominal pain, and loss of smell/taste are reported more often in patients with non-severe illness.

We report a higher prevalence of COVID-19 in men compared to women. An analysis of 14,712 patients revealed men to have significantly higher mortality than women even after adjusting for comorbidities [171]. Gender differences have been reported in the prior influenza pandemic, suggesting that men are more susceptible to viral respiratory illness; this is attributed to females generating stronger innate and adaptive immune responses [172, 173]. Thus, it could be why SARS-CoV-2, being a respiratory virus, was noted to have a higher prevalence in men in our study. One study evaluating 524 SARS-CoV-2 patients ages 51 to 70 found that males were significantly more likely to be hospitalized and had increased mortality regardless of age [174]. It could be hypothesized that women have a robust immune response to viruses as seen with the influenza virus as well; hence that could be the reason for the protection of females against SARS-CoV 2 infection.

We found the most common comorbidities to be hypertension and diabetes; these results are consistent with prior studies with a similar prevalence of hypertension and diabetes ranging from 13% to 27% and 7% to 12%, respectively [4, 175]. The slightly higher prevalence of hypertension and diabetes in this study could be attributed to the inclusion of studies worldwide. In contrast, prior studies included only studies from China. The prevalence of obesity was 27.9% from 9 studies; interestingly, all these studies were from the US. Obesity has also been postulated to be a risk factor for COVID-19 by the dysregulation of the immune system due to excess adiposity and decreased diaphragm contractility [176]. Smoking was more common in non-severe patients; the “smoker’s paradox” has been proposed as a possible mechanism suggesting smoking to have a protective effect, although this hypothesis continues to remain controversial [177].

Hypertension, hyperlipidemia, smoking, diabetes mellitus, and obesity are well-known cardiovascular risk factors [178]. Heart disease, stroke, and diabetes are known risk factors for influenza and its complications. SARS-CoV-2, being a respiratory virus, could also be hypothesized to have a similar risk factor [179]. Several hypotheses have been proposed for the cardiovascular complications of SARS-CoV-2, including angiotensin-converting enzyme-2 mediated cardiac damage, direct viral injury to myocardium, and hypoxemia mediated damage. However, none of these hypotheses have been proven yet [6, 180, 181]. Our findings suggest a higher prevalence of cardiovascular comorbidities in severe cases, which could be likely because of myocardial injury in these patients. The presence of comorbidities, including hypertension, diabetes mellitus, and atherosclerotic disease, was noted to be significantly higher in the severely ill patient population, which is corroborated by prior studies [19, 24, 35, 182].

Our study is in concordance with a prior meta-analysis of 43 studies with 3600 patients reporting fever, cough, and fatigue to be the most common clinical symptoms, suggesting COVID-19 to have primary respiratory system involvement [4]. In our study, fever was the most common presenting symptom as well [4, 35, 54, 109]. Respiratory symptoms of shortness of breath, cough, sputum production, and rhinorrhea were more common in severe illnesses, whereas non-respiratory symptoms are more common in non-severe disease. This could be because dyspnea and the need for supplemental oxygen are the criteria for severe illness. Initial studies were suggestive of COVID-19 being primarily a respiratory illness; however, recent studies suggest COVID-19 to be a multi-system disorder with the involvement of cardiovascular, gastrointestinal, musculoskeletal, and nervous systems. We report the involvement of respiratory, cardiovascular, gastrointestinal, musculoskeletal, and nervous systems, suggesting that COVID-19 is a multi-system disease with primary respiratory system involvement.

Our study reports a low prevalence (25.1% in 7952 from 13 studies) of loss of smell or taste; this is likely because of the inclusion of outpatient and survey studies in our review. A review focusing on olfactory dysfunction reported that up to 80% of patients with COVID-19 might develop subjective olfactory dysfunction in the disease’s initial stages [183]. The lower prevalence in our study can be attributed to the inclusion of more inpatient studies in our analysis, as loss of smell tends to be an early-onset symptom and not recognized in inpatients. A review focusing on musculoskeletal symptoms of 12,046 patients reported occurrence of fatigue in 25.6% and arthralgia and/or myalgia in 15.5% of patients. Our study also showed a similar prevalence of these symptoms, although they seem to be nonspecific and represent viral prodromal symptoms for most of the respiratory viruses [184].

Our study’s strength lies in its large patient population of more than 40,000 cases, including inpatients and outpatients, severe and non-severe cases, and spread over multiple continents. Our study has certain limitations as the majority of studies included in our study are observational. Even though our study included patients across the world, the majority of studies originate from China. Of concern, many of the studies were incomplete and did not include a comprehensive picture of the patients such as outcomes on discharge. Additionally, most of the studies were in inpatient settings, thus under-representing cases within the community. Lastly, the literature evolving around COVID-19 is very dynamic and rapidly evolving, especially in terms of outcomes.

In conclusion, the prevalence of COVID-19 was found to be higher in men. Hypertension, diabetes, and atherosclerotic diseases are common comorbidities globally, and obesity is the second most common in the US. There is a higher prevalence of comorbid hypertension and diabetes amongst severely ill patients and a higher prevalence of fever, myalgia/arthralgia, shortness of breath, and cough symptoms in severely ill patients. We believe that further high-quality prospective studies are needed to identify the demographics and regional differences and ascertain characteristics of outpatient COVID-19 individuals.

Conflict of interest

The authors declare no conflict of interest.