Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
[Preprint]. 2020 Apr 21:3566166.
doi: 10.2139/ssrn.3566166.

Clinical Features of COVID-19 and Factors Associated with Severe Clinical Course: A Systematic Review and Meta-analysis

Ashish Kumar  1 , Anil Arora  1 , Praveen Sharma  1 , Shrihari Anil Anikhindi  1 , Naresh Bansal  1 , Vikas Singla  1 , Shivam Khare  1 , Abhishyant Srivastava  1
Affiliations

Clinical Features of COVID-19 and Factors Associated with Severe Clinical Course: A Systematic Review and Meta-analysis

Ashish Kumar et al. SSRN. .

Abstract

Background: COVID-19 is a new disease which has become a global pandemic, and is caused by a novel coronavirus, SARS-CoV-2. The disease is still not very well characterized, and factors associated with severe clinical course are not well known.

Methods: The main objectives were to determine the demographic, clinical and laboratory manifestations of COVID-19 and to identify the factors associated with severe clinical course. We searched the PubMed for studies published between Jan 1, 2020 and Mar 17, 2020, and included them if they were in English language, published in full, were retrospective or prospective observational or case control study with data on clinical, laboratory and imaging features of adult patients with COVID-19 disease from single or multiple centers. Studies that included exclusively pediatric patients were excluded. The demographic, clinical and laboratory data was displayed as n (%) or mean (SD). The meta-analysis on factors associated with severe clinical course was performed using the random effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated as the effect sizes.

Findings: We included 58 studies (6892 patients) for the systematic review on clinical manifestations and 21 studies (3496 patients) for meta-analysis on factors associated with severe clinical course. The mean age of patients with COVID-19 is 49.7±16.3 years with a male to female ratio of 1.2:1. Common symptoms and their frequency are: fever (83.4%), cough (60.5%), fatigue (33.8%), sputum (28.9%), dyspnea (22.1%), myalgia (20.6%), chest tightness / pain (16.3%), sore throat (13.5%), headache (11.2%), diarhhea (7.5%), nasal congestion / rhinorrhea (6.7%), nausea / vomiting (5.6%), pain abdomen (4.6%), and hemoptysis (1.7%). The comorbidities associated with COVID-19 are: hypertension (18.4%), diabetes mellitus (9.8%), cardiovascular diseases (8.8%), endocrine diseases (5.8%), gastrointestinal diseases (5%), CLD (3%), and COPD (2.8%). Among the laboratory parameters WBC was low in 27%, high in 9%, platelets were low in 22.9%, creatinine was high in 6.5%, AST was high in 25.3%, ALT was high in 22.7%, bilirubin was high in 8.8%, albumin was low 60.1%, CT chest was abnormal in 89%, CRP was high in 67.5%, LDH was high in 52%, D-dimer was high in 34.8%, CK was high in 14.4%, and procalcitonin was high in 15.4%. Factors significantly associated severe clinical course (with their ORs) are as follows: High CRP (5.78), high procalcitonin (5.45), age >60 (4.82), dyspnea (4.66), high LDH (4.59), COPD (4.37), low albumin (4.34), high D-dimer (4.03), cardiac disease (3.88), low lymphocyte count (3.22), any associated comorbidity (3.16), diabetes mellitus (3.11), high WBC count (2.67), high bilirubin level (2.55), high creatinine (2.34), high AST (2.31), hypertension (2.30), low platelets (1.78), High ALT (1.69), high CK (1.66), fever spikes ≥39°C (1.59), diarrhea (1.55), male gender (1.47), and sputum (1.35).

Interpretation: Identification of these factors associated with severe COVID-19 will help the physicians working at all levels of healthcare (primary, secondary, tertiary and ICU) in determining which patients need home care, hospital care, HDU care, and ICU admission; and thus, prioritize the scarce healthcare resource use more judiciously. Many of these identified factors can also help the public at large in the current COVID-19 epidemic setting, to judge when they should seek immediate medical care.

Keywords: 2019-nCoV; COVID-19; Coronavirus; SARS-CoV-2; nCoV-2019; novel coronavirus.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests We declare no competing interests.

Figures

Figure 1:
Figure 1:
PRISMA flow diagram depicting the flow of information through different phases of a systematic review.
Figure 2:
Figure 2:
Clinical course of the patients.
Figure 3:
Figure 3:
Mean age of patients with good and severe clinical course.
Figure 4:
Figure 4:
Forest plot showing pooled odds ratio for patients with higher age (≥60 years) developing severe clinical course.
Figure 5:
Figure 5:
Forest plot showing pooled odds ratio for male gender developing severe clinical course.
Figure 6:
Figure 6:
Forest plot showing pooled odds ratio for patients having any comorbidity developing severe clinical course.
Figure 7:
Figure 7:
Forest plot showing pooled odds ratio for patients with diabetes mellitus developing severe clinical course.
Figure 8:
Figure 8:
Forest plot showing pooled odds ratio for patients with hypertension developing severe clinical course.
Figure 9:
Figure 9:
Forest plot showing pooled odds ratio for patients with cardiovascular disease developing severe clinical course.
Figure 10:
Figure 10:
Forest plot showing pooled odds ratio for patients with COPD developing severe clinical course.
Figure 11:
Figure 11:
Forest plot showing pooled odds ratio of fever being associated with severe clinical course.
Figure 12:
Figure 12:
Forest plot showing pooled odds ratio of high temperature (≥39°C) being associated with severe clinical course.
Figure 13:
Figure 13:
Forest plot showing pooled odds ratio of cough being associated with severe clinical course.
Figure 14:
Figure 14:
Forest plot showing pooled odds ratio of sputum production being associated with severe clinical course.
Figure 15:
Figure 15:
Forest plot showing pooled odds ratio of dyspnea being associated with severe clinical course.
Figure 16:
Figure 16:
Forest plot showing pooled odds ratio of diarrhea being associated with severe clinical course.
Figure 17:
Figure 17:
Forest plot showing pooled odds ratio of higher than normal values of WBC count being associated with severe clinical course.
Figure 18:
Figure 18:
Forest plot showing pooled odds ratio of lower than normal values of lymphocyte count being associated with severe clinical course.
Figure 19:
Figure 19:
Forest plot showing pooled odds ratio of lower than normal values of platelet count being associated with severe clinical course.
Figure 20:
Figure 20:
Comparison of mean hemoglobin values between patients with good and severe clinical course.
Figure 21:
Figure 21:
Forest plot showing pooled odds ratio of high creatinine values being associated with severe clinical course.
Figure 22:
Figure 22:
Forest plot showing pooled odds ratio of higher than normal values of AST being associated with severe clinical course.
Figure 23:
Figure 23:
Forest plot showing pooled odds ratio of higher than normal values of ALT being associated with severe clinical course.
Figure 24:
Figure 24:
Forest plot showing pooled odds ratio of higher than normal values of serum bilirubin being associated with severe clinical course.
Figure 25:
Figure 25:
Forest plot showing pooled odds ratio of lower than normal values of serum albumin being associated with severe clinical course.
Figure 26:
Figure 26:
Forest plot showing pooled odds ratio of higher than normal values of C-reactive protein being associated with severe clinical course.
Figure 27:
Figure 27:
Forest plot showing pooled odds ratio of higher than normal values of D-dimer being associated with severe clinical course.
Figure 28:
Figure 28:
Forest plot showing pooled odds ratio of high LDH being associated with severe clinical course.
Figure 29:
Figure 29:
Forest plot showing pooled odds ratio of high serum procalcitonin being associated with severe clinical course.
Figure 30:
Figure 30:
Forest plot showing pooled odds ratio of high serum creatine kinase being associated with severe clinical course.
Figure 31:
Figure 31:
Summary forest plot showing odds ratios of all the factors associated with severe clinical course.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Johns Hopkins Coronavirus Resource Center. Johns Hopkins Coronavirus Resource Center. https://coronavirus.jhu.edu/ (accessed March 30, 2020).
    1. Mahase E. Covid-19: WHO declares pandemic because of ‘alarming levels’ of spread, severity, and inaction. BMJ 2020; 368: m1036. - PubMed
    1. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395: 565–74. - PMC - PubMed
    1. Sun P, Qie S, Liu Z, Ren J, Li K, Xi J. Clinical characteristics of hospitalized patients with SARS-CoV-2 infection: A single arm meta-analysis. J Med Virol 2020; published online Feb 28. DOI:10.1002/jmv.25735 - DOI - PMC - PubMed
    1. Li L-Q, Huang T, Wang Y-Q, et al. 2019 novel coronavirus patients’ clinical characteristics, discharge rate and fatality rate of meta-analysis. J Med Virol 2020; published online March 12. DOI:10.1002/jmv.25757 - DOI - PMC - PubMed

Publication types

LinkOut - more resources