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Meta-Analysis
. 2021 Feb 23;2(2):CD013665.
doi: 10.1002/14651858.CD013665.pub2.

Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19

Thomas Struyf  1 , Jonathan J Deeks  2   3 , Jacqueline Dinnes  4   3 , Yemisi Takwoingi  2   3 , Clare Davenport  2   3 , Mariska Mg Leeflang  5   6 , René Spijker  7   8 , Lotty Hooft  9 , Devy Emperador  10 , Julie Domen  1 , Sebastiaan R A Horn  11 , Ann Van den Bruel  1 ; Cochrane COVID-19 Diagnostic Test Accuracy Group  3
Affiliations
Meta-Analysis

Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19

Thomas Struyf et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: The clinical implications of SARS-CoV-2 infection are highly variable. Some people with SARS-CoV-2 infection remain asymptomatic, whilst the infection can cause mild to moderate COVID-19 and COVID-19 pneumonia in others. This can lead to some people requiring intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever, cough, or loss of smell or taste, and signs such as oxygen saturation are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19, or select patients for further testing. This is an update of this review, the first version of which published in July 2020.

Objectives: To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19.

Search methods: For this review iteration we undertook electronic searches up to 15 July 2020 in the Cochrane COVID-19 Study Register and the University of Bern living search database. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions.

Selection criteria: Studies were eligible if they included patients with clinically suspected COVID-19, or if they recruited known cases with COVID-19 and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies in hospitalised patients were only included if symptoms and signs were recorded on admission or at presentation. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards.

Data collection and analysis: Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. We presented sensitivity and specificity in paired forest plots, in receiver operating characteristic space and in dumbbell plots. We estimated summary parameters using a bivariate random-effects meta-analysis whenever five or more primary studies were available, and whenever heterogeneity across studies was deemed acceptable.

Main results: We identified 44 studies including 26,884 participants in total. Prevalence of COVID-19 varied from 3% to 71% with a median of 21%. There were three studies from primary care settings (1824 participants), nine studies from outpatient testing centres (10,717 participants), 12 studies performed in hospital outpatient wards (5061 participants), seven studies in hospitalised patients (1048 participants), 10 studies in the emergency department (3173 participants), and three studies in which the setting was not specified (5061 participants). The studies did not clearly distinguish mild from severe COVID-19, so we present the results for all disease severities together. Fifteen studies had a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. This may have especially influenced the sensitivity of those features used in referral protocols, such as fever and cough. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional 12 studies, we were unable to assess the risk for selection bias. This makes it very difficult to judge the validity of the diagnostic accuracy of the signs and symptoms from these included studies. The applicability of the results of this review update improved in comparison with the original review. A greater proportion of studies included participants who presented to outpatient settings, which is where the majority of clinical assessments for COVID-19 take place. However, still none of the studies presented any data on children separately, and only one focused specifically on older adults. We found data on 84 signs and symptoms. Results were highly variable across studies. Most had very low sensitivity and high specificity. Only cough (25 studies) and fever (7 studies) had a pooled sensitivity of at least 50% but specificities were moderate to low. Cough had a sensitivity of 67.4% (95% confidence interval (CI) 59.8% to 74.1%) and specificity of 35.0% (95% CI 28.7% to 41.9%). Fever had a sensitivity of 53.8% (95% CI 35.0% to 71.7%) and a specificity of 67.4% (95% CI 53.3% to 78.9%). The pooled positive likelihood ratio of cough was only 1.04 (95% CI 0.97 to 1.11) and that of fever 1.65 (95% CI 1.41 to 1.93). Anosmia alone (11 studies), ageusia alone (6 studies), and anosmia or ageusia (6 studies) had sensitivities below 50% but specificities over 90%. Anosmia had a pooled sensitivity of 28.0% (95% CI 17.7% to 41.3%) and a specificity of 93.4% (95% CI 88.3% to 96.4%). Ageusia had a pooled sensitivity of 24.8% (95% CI 12.4% to 43.5%) and a specificity of 91.4% (95% CI 81.3% to 96.3%). Anosmia or ageusia had a pooled sensitivity of 41.0% (95% CI 27.0% to 56.6%) and a specificity of 90.5% (95% CI 81.2% to 95.4%). The pooled positive likelihood ratios of anosmia alone and anosmia or ageusia were 4.25 (95% CI 3.17 to 5.71) and 4.31 (95% CI 3.00 to 6.18) respectively, which is just below our arbitrary definition of a 'red flag', that is, a positive likelihood ratio of at least 5. The pooled positive likelihood ratio of ageusia alone was only 2.88 (95% CI 2.02 to 4.09). Only two studies assessed combinations of different signs and symptoms, mostly combining fever and cough with other symptoms. These combinations had a specificity above 80%, but at the cost of very low sensitivity (< 30%).

Authors' conclusions: The majority of individual signs and symptoms included in this review appear to have very poor diagnostic accuracy, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out COVID-19. The presence of anosmia or ageusia may be useful as a red flag for COVID-19. The presence of fever or cough, given their high sensitivities, may also be useful to identify people for further testing. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19, are still urgently needed. Results from such studies could inform subsequent management decisions.

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Conflict of interest statement

Thomas Struyf: none known

Jonathan J Deeks: none known

Jacqueline Dinnes: none known

Yemisi Takwoingi: none known

Clare Davenport: none known

Mariska MG Leeflang: none known

René Spijker: the Dutch Cochrane Centre (DCC) has received grants for performing commissioned systematic reviews. In no situation did the commissioner have any influence on the results of the work.

Lotty Hooft: none known

Devy Emperador: is employed by FIND. FIND is a global non‐for profit product development partnership and WHO Diagnostic Collaboration Centre. It is FIND’s role to accelerate access to high quality diagnostic tools for low resource settings and this is achieved by supporting both R&D and access activities for a wide range of diseases, including COVID‐19. FIND has several clinical research projects to evaluate multiple new diagnostic tests against published Target Product Profiles that have been defined through consensus processes. These studies are for diagnostic products developed by private sector companies who provide access to know‐how, equipment/reagents, and contribute through unrestricted donations as per FIND policy and external SAC review.

Julie Domen: none known

Sebastiaan Horn: none known

Ann Van den Bruel: none known

Figures

1
1
Flow diagram.
2
2
'Risk of bias' and applicability concerns graph: review authors' judgements about each domain presented as percentages across included studies
3
3
'Risk of bias' and applicability concerns summary: review authors' judgements about each domain for each included study
4
4
Forest plot of upper respiratory tract symptoms (cross‐sectional studies)
5
5
Forest plot of lower respiratory tract symptoms (cross‐sectional studies)
6
6
Forest plot of systemic signs and symptoms (cross‐sectional studies)
7
7
Forest plot of gastrointestinal signs and symptoms (cross‐sectional studies)
8
8
Forest plot of cardiovascular signs and symptoms (cross‐sectional studies)
9
9
Forest plot of olfactory symptoms (cross‐sectional studies)
10
10
Summary ROC plot of upper respiratory tract symptoms (cross‐sectional studies)
11
11
Summary ROC plot of lower respiratory tract symptoms (cross‐sectional studies)
12
12
Summary ROC plot of systemic signs and symptoms (cross‐sectional studies)
13
13
Summary ROC plot of gastrointestinal signs and symptoms (cross‐sectional studies)
14
14
Summary ROC plot of dyspnoea
15
15
Summary ROC plot of fever. Summary point and 95% confidence region for prospective studies only
16
16
Summary ROC plot of anosmia
17
17
Summary ROC plot of sore throat (cross‐sectional studies)
18
18
Summary ROC plot of ageusia
19
19
Summary ROC plot of anosmia or ageusia
20
20
Summary ROC plot of cough (cross‐sectional studies)
21
21
Summary ROC Plot of fatigue
22
22
Summary ROC plot of headache. Summary point only estimable in prospective studies
23
23
Forest plot of tests: cough (non‐cross‐sectional study), sore throat (non‐cross‐sectional study), positive auscultation findings (non‐cross‐sectional study), rhinorrhoea (non‐cross‐sectional study), dyspnoea (non‐cross‐sectional study), sneezing (non‐cross‐sectional study), nasal congestion (non‐cross‐sectional study), sputum production (non‐cross‐sectional study), pulmonary auscultation (crackling) bilateral (non‐cross‐sectional study), pulmonary auscultation (crackling unilateral; non‐cross‐sectional study), pulmonary auscultation (rhonchi; non‐cross‐sectional study), pulmonary auscultation: sibilant (non‐cross‐sectional study)
24
24
Forest plot of tests: fever (non‐cross‐sectional study), fatigue (non‐cross‐sectional study), myalgia or arthralgia (non‐cross‐sectional study), headache (non‐cross‐sectional study), asthenia (non‐cross‐sectional study), fever (subjective, non‐cross‐sectional study)), arthralgia (non‐cross‐sectional study)
25
25
Forest plot of tests: diarrhoea (non‐cross‐sectional study), nausea/vomiting (non‐cross‐sectional study), gastrointestinal symptoms (not specified; non‐cross‐sectional study), nausea (non‐cross‐sectional study), vomiting (non‐cross‐sectional study), abdominal pain (non‐cross‐sectional study)
26
26
Forest plot of chest tightness (non‐cross‐sectional study)
27
27
Forest plot of tests: ageusia (non‐cross‐sectional study), dysgeusia (non‐cross‐sectional study), anosmia (non‐cross‐sectional study), anosmia or dysgeusia (non‐cross‐sectional study), dysgeusia or ageusia (non‐cross‐sectional study), hyposmia (non‐cross‐sectional study)
28
28
Dumbbell plot: olfactory symptoms (cross‐sectional studies only). This plot shows how disease probability changes after a positive test result (red dot with plus sign) or after a negative test (green dot with minus sign). Pre‐test probability or prevalence is the blue dot
29
29
Dumbbell plot: fever. This plot shows how disease probability changes after a positive test result (red dot with plus sign) or after a negative test (green dot with minus sign). Pre‐test probability or prevalence is the blue dot
30
30
Dumbbell plot: cough. This plot shows how disease probability changes after a positive test result (red dot with plus sign) or after a negative test (green dot with minus sign). Pre‐test probability or prevalence is the blue dot
31
31
Directed acyclic graph on cough
1
1. Test
Fever
2
2. Test
Cough
3
3. Test
Dyspnoea
4
4. Test
Sore throat
5
5. Test
Diarrhoea
6
6. Test
Headache
7
7. Test
Myalgia
8
8. Test
Fatigue
9
9. Test
Sputum production
10
10. Test
Anosmia
11
11. Test
Nausea or vomiting
12
12. Test
Ageusia
13
13. Test
Anosmia or ageusia
14
14. Test
Chest tightness
15
15. Test
Chills
16
16. Test
Nasal congestion
17
17. Test
Abdominal pain
18
18. Test
Rhinorrhea
19
19. Test
Myalgia or arthralgia
20
20. Test
Nasal symptoms
21
21. Test
Nausea
22
22. Test
Haemoptysis
23
23. Test
Gastrointestinal symptoms (not specified)
24
24. Test
Dry cough
25
25. Test
Vomiting
26
26. Test
Skin lesions
27
27. Test
Anosmia and ageusia
28
28. Test
Anosmia or dysgeusia
29
29. Test
Anorexia
30
30. Test
Coryza
31
31. Test
Wheeze
32
32. Test
Myalgia or fatigue
33
33. Test
Fever (subjective)
34
34. Test
High fever (>=38.5°C)
35
35. Test
Altered mentation
36
36. Test
Weakness or fatigue
37
37. Test
Tachycardia
38
38. Test
Loss of appetite
39
39. Test
Hypoxia
41
41. Test
Respiratory symptoms (not specified))
42
42. Test
Rhinitis or pharyngitis
43
43. Test
Sinusitis
44
44. Test
Isolated fever
45
45. Test
Low body temperature
46
46. Test
Shivers
47
47. Test
Arthralgia
48
48. Test
Systemic soreness (malaise/myalgia/arthralgia)
49
49. Test
Abdominal distension
50
50. Test
Low systolic blood pressure
51
51. Test
High systolic blood pressure
52
52. Test
Palpitations
53
53. Test
Tachypnea
54
54. Test
Lethargy
55
55. Test
Hyposmia
56
56. Test
Dysgeusia
57
57. Test
Anosmia and dysgeusia
58
58. Test
Rash
59
59. Test
Isolated headache
60
60. Test
Diarrhea and nausea
61
61. Test
Dizziness or syncope
62
62. Test
Earache
63
63. Test
Enlargement of lymph nodes
64
64. Test
Stomachache
65
65. Test
Arthralgia
66
66. Test
Unconsciousness
67
67. Test
Aversion to cold
68
68. Test
Xerostomia
69
69. Test
Hypersomnia
70
70. Test
Sneezing
71
71. Test
Change to chronic cough
72
72. Test
Dizziness
73
73. Test
Positive auscultation findings
74
74. Test
Pulmonary auscultation: crackling bilateral
75
75. Test
Pulmonary auscultation: crackling unilateral
76
76. Test
Conjunctivitis
77
77. Test
Myalgia and asthenia and fever
78
78. Test
Fever and cough
79
79. Test
Fever and cough and sore throat
80
80. Test
Fever and cough and dyspnea
81
81. Test
Cough and fever and sputum production
82
82. Test
Cough and fever and sputum production and dyspnea
83
83. Test
Sore throat and nasal congestion and sneezing and mild fever
84
84. Test
Dyspnea and cough and fever and low oxygen saturation
85
85. Test
Cough (non‐cross‐sectional study)
86
86. Test
Sore throat (non‐cross‐sectional study)
87
87. Test
Positive auscultation findings (non‐cross‐sectional study)
88
88. Test
Rhinorrhoea (non‐cross‐sectional study)
89
89. Test
Dyspnoea (non‐cross‐sectional study)
90
90. Test
Ageusia (non‐cross‐sectional study)
91
91. Test
Chest tightness (non‐cross‐sectional study)
92
92. Test
Fever (non‐cross‐sectional study)
93
93. Test
Fatigue (non‐cross‐sectional study)
94
94. Test
Myalgia or arthralgia (non‐cross‐sectional study)
95
95. Test
Headache (non‐cross‐sectional study)
96
96. Test
Diarrhoea (non‐cross‐sectional study)
97
97. Test
Nausea/vomiting (non‐cross‐sectional study)
98
98. Test
Red eyes (non‐cross‐sectional study)
99
99. Test
Gastrointestinal symptoms, not specified (non‐cross‐sectional study)
TST-100
TST-100. Test
Asthenia (non‐cross‐sectional study)
TST-101
TST-101. Test
Fever (subjective, non‐cross‐sectional study))
TST-102
TST-102. Test
Arthralgia (non‐cross‐sectional study)
TST-103
TST-103. Test
Sneezing (non‐cross‐sectional study)
TST-104
TST-104. Test
Rash (non‐cross‐sectional study)
TST-105
TST-105. Test
Loss of temp. sens. in face (non‐cross‐sectional study)
TST-106
TST-106. Test
Vertigo or dizziness (non‐cross‐sectional study)
TST-107
TST-107. Test
Blurred vision (non‐cross‐sectional study)
TST-108
TST-108. Test
Nasal congestion (non‐cross‐sectional study)
TST-109
TST-109. Test
Dysgeusia (non‐cross‐sectional study)
TST-110
TST-110. Test
Anosmia (non‐cross‐sectional study)
TST-111
TST-111. Test
Loss of appetite (non‐cross‐sectional study)
TST-112
TST-112. Test
Myalgia (non‐cross‐sectional study)
TST-113
TST-113. Test
Anosmia or dysgeusia (non‐cross‐sectional study)
TST-114
TST-114. Test
Sputum production (non‐cross‐sectional study)
TST-115
TST-115. Test
Chills (non‐cross‐sectional study)
TST-116
TST-116. Test
Nausea (non‐cross‐sectional study)
TST-117
TST-117. Test
Vomiting (non‐cross‐sectional study)
TST-119
TST-119. Test
Abdominal pain (non‐cross‐sectional study)
TST-120
TST-120. Test
Conjunctival hyperemia (non‐cross‐sectional study)
TST-121
TST-121. Test
Diffuse headache (non‐cross‐sectional study)
TST-122
TST-122. Test
Frontal headache (non‐cross‐sectional study)
TST-123
TST-123. Test
Epistaxis (non‐cross‐sectional study)
TST-124
TST-124. Test
Dry eyes (non‐cross‐sectional study)
TST-125
TST-125. Test
Haemoptysis (non‐cross‐sectional study)
TST-126
TST-126. Test
Hearing loss (non‐cross‐sectional study)
TST-127
TST-127. Test
Pulmonary auscultation: crackling bilateral (non‐cross‐sectional study)
TST-128
TST-128. Test
Pulmonary auscultation: crackling unilateral (non‐cross‐sectional study)
TST-129
TST-129. Test
Pulmonary auscultation: rhonchi (non‐cross‐sectional study)
TST-130
TST-130. Test
Pulmonary auscultation: sibilant (non‐cross‐sectional study)
TST-131
TST-131. Test
Tachypnea (non‐cross‐sectional study)
TST-132
TST-132. Test
Tinnitus (non‐cross‐sectional study)
TST-133
TST-133. Test
Tearing (non‐cross‐sectional study)
TST-134
TST-134. Test
Dysgeusia or ageusia (non‐cross‐sectional study)
TST-135
TST-135. Test
Hyposmia (non‐cross‐sectional study)
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References

References to studies included in this review

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    1. Shah SJ, Barish PN, Prasad PA, Kistler AL, Neff N, Kamm J, et al. Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: A retrospective cohort study of patients with and without COVID-19. EClinicalMedicine 2020;27. [DOI: ] - PMC - PubMed
Song 2020a {published data only}
    1. Song CY, Xu J, He JQ, Lu YQ. COVID-19 early warning score: a multi-parameter screening tool to identify highly suspected patients. medRxiv [Preprint] 2020. [DOI: 10.1101/2020.03.05.20031906] - DOI
Sun 2020 {published data only}
    1. Sun Y, Koh V, Marimuthu K, Ng OT, Young B, Vasoo S, et al. Epidemiological and clinical predictors of COVID-19. Clinical Infectious Diseases 2020;71(15):786-92. [DOI: 10.1093/cid/ciaa322] - DOI - PMC - PubMed
Tolia 2020 {published data only}
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Tordjman 2020 {published data only}
    1. Tordjman M, Mekki A, Mali RD, Saab I, Chassagnon G, Guillo E, et al. Pre-test probability for SARS-Cov-2-related infection score: the PARIS score. PLOS ONE 2020;15(12):e0243342. [DOI: ] - PMC - PubMed
Trubiano 2020 {published data only}
    1. Trubiano JA, Vogrin S, Smibert OC, Marhoon N, Alexander AA, Chua KY, et al. COVID-MATCH65 - a prospectively derived clinical decision rule for severe acute respiratory syndrome coronavirus 2. PLoS One 10/12/2020;15(12):e0243414. [DOI: ] - PMC - PubMed
Tudrej 2020 {published data only}
    1. Tudrej B, Sebo P, Lourdaux J, Cuzin C, Floquet M, Haller DM, et al. Self- reported loss of smell and taste in SARS-CoV-2 patients: primary care data to guide future early detection strategies. Journal of General Internal Medicine 2020;35(8):2502-4. - PMC - PubMed
Wee 2020 {published data only}
    1. Wee LE, Chan YZ, Teo NY, Cherng BZ, Thien SY, Wong M, et al. The role of self-reported olfactory and gustatory dysfunction as a screening criterion for suspected COVID-19. European Archives of Oto-Rhino-Laryngology 2020;277(8):2389-90. [DOI: 10.1007/s00405-020-05999-5] - DOI - PMC - PubMed
Wei 2020 {published data only}
    1. Wei Y, Lu Y, Xia L, Yuan X, Li G, Li X, et al. Analysis of 2019 novel coronavirus infection and clinical characteristics of outpatients: an epidemiological study from a fever clinic in Wuhan, China. Journal of Medical Virology 2020;92:2758-67. - PMC - PubMed
Xie 2020 {published data only}
    1. Xie S, Zhang G, Yu H, Wang J, Wang S, Tang G, et al. The epidemiologic and clinical features of suspected and confirmed cases of imported 2019 novel coronavirus pneumonia in north Shanghai, China. Annals of Translational Medicine 2020;8(10):637. - PMC - PubMed
Yan 2020 {published data only}
    1. Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS. Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms. International Forum of Allergy & Rhinology 2020;10(7):806-13. [DOI: 10.1002/alr.22579] - DOI - PMC - PubMed
Yang 2020 {unpublished data only}
    1. Yang Z, Lin D, Chen X, Qiu J, Li S, Huang R, et al. Distinguishing COVID-19 from influenza pneumonia in the early stage through CT imaging and clinical features. medRxiv [Preprint] 2020. [DOI: ] - PMC - PubMed
Yombi 2020 {published data only}
    1. Yombi JC, De Greef J, Marsin A-S, Simon A, Rodriguez-Villalobos H, Penaloza A, et al. Symptom-based screening for COVID-19 in health care workers: the importance of fever. Journal of Hospital Infection 2020;105(3):428-9. - PMC - PubMed
Zavascki 2020 {published data only}
    1. Zavascki AP, Gazzana MB, Bidart JP, Fernandes PS, Galiotto A, Kawski CT, et al. Development of a predictive score for COVID-19 diagnosis based on demographics and symptoms in patients attended at a dedicated screening unit. medRxiv [Preprint] 2020. [DOI: ]
Zayet 2020a {published data only}
    1. Zayet S, Kadiane-Oussou NJ, Lepiller Q, Zahra H, Royer PY, Toko L, et al. Clinical features of COVID-19 and influenza: a comparative study on Nord Franche-Comte cluster. Microbes and Infection 2020;22(9):481-8. - PMC - PubMed
Zayet 2020b {published data only}
    1. Zayet S, Klopfenstein T, Mercier J, Kadiane-Oussou NJ, Lan Cheong Wah L, Royer PY, et al. Contribution of anosmia and dysgeusia for diagnostic of COVID-19 in outpatients. Infection 2020;14:1-5. - PMC - PubMed
Zhao 2020 {published data only}
    1. Zhao D, Yao F, Wang L, Zheng L, Gao Y, Ye J, et al. A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias. Clinical Infectious Diseases 2020;71(15):756-61. [DOI: 10.1093/cid/ciaa247] - DOI - PMC - PubMed
Zhu 2020 {published data only}
    1. Zhu W, Xie K, Lu H, Xu L, Zhou S, Fang S. Initial clinical features of suspected coronavirus disease 2019 in two emergency departments outside of Hubei, China. Journal of Medical Virology 2020;92(9):1525-32. [DOI: 10.1002/jmv.25763 ] - PMC - PubMed
Zimmerman 2020 {published data only}
    1. Zimmerman RK, Nowalk MP, Bear T, Taber R, Sax TM, Eng H, et al. Proposed clinical indicators for efficient screening and testing for COVID-19 infection using Classification and Regression Trees (CART) analysis. Hum Vaccin Immunother 2020:1-4. [DOI: ] - PMC - PubMed

References to studies excluded from this review

Guan 2020 {published data only}
    1. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of 2019 novel coronavirus infection in China. medRxiv [Preprint] 2020. [DOI: 10.1101/2020.02.06.20020974] - DOI - PubMed
Soares 2020 {published data only}
    1. Soares F, Villavicencio A, Anzanello MJ, Fogliatto FS, Idiart M, Stevenson M. A novel high specificity COVID-19 screening method based on simple blood exams and artificial intelligence. medRxiv [Preprint] 2020. [DOI: 10.1101/2020.04.10.20061036] - DOI
Song 2020b {published data only}
    1. Song F, Shi N, Shan F, Zhang Z, Shen J, Lu H, et al. Emerging coronavirus 2019-nCoV pneumonia. Radiology 2020;295(1):200274. [DOI: 10.1148/radiol.2020200274] - DOI - PMC - PubMed
Wang 2020 {published data only}
    1. Wang Y, Kang H, Liu X, Tong Z. Combination of RT-qPCR testing and clinical features for diagnosis of COVID-19 facilitates management of SARS-CoV-2 outbreak. Journal of Medical Virology 2020;92(6). [DOI: 10.1002/jmv.25721 10.1002/jmv.25721] - PMC - PubMed

References to ongoing studies

ChiCTR2000029462 {published data only}
    1. ChiCTR2000029462. Study for clinical characteristics and distribution of TCM syndrome of novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showproj.aspx?proj=48922 (first received 27 April 2020).
ChiCTR2000029734 {published data only}
    1. ChiCTR2000029734. Epidemiological investigation and clinical characteristics analysis of novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showproj.aspx?proj=48868 (first received 27 April 2020).
ChiCTR2000029770 {published data only}
    1. ChiCTR2000029770. Study for epidemiology, diagnosis and treatment of novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/hvshowproject.aspx?id=23744 (first received 27 April 2020).
ChiCTR2000029839 {published data only}
    1. ChiCTR2000029839. An observational study on the clinical characteristics, treatment and outcome of novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showproj.aspx?proj=49439 (first received 27 April 2020).
ChiCTR2000029865 {published data only}
    1. ChiCTR2000029865. Descriptive study on the clinical characteristics and outcomes of novel coronavirus pneumonia (COVID-19) in cardiovascular patients. www.chictr.org.cn/showproj.aspx?proj=49545 (first received 27 April 2020).
ChiCTR2000029866 {published data only}
    1. ChiCTR2000029866. Early warning prediction of patients with severe novel coronavirus pneumonia (COVID-19) based on multiomics. www.chictr.org.cn/showproj.aspx?proj=49519 (first received 27 April 2020).
ChiCTR2000029959 {published data only}
    1. ChiCTR2000029959. Clinical observation and research of severe acute respiratory syndrome coronavirus 2(COVID-19) infection in perinatal newborns. www.chictr.org.cn/showproj.aspx?proj=49636 (first received 27 April 2020).
ChiCTR 2000030096 {published data only}
    1. ChiCTR 2000030096. Study for establishment of correlation between virological dynamics and clinical features in novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showprojen.aspx?proj=49794 (first received 27 April 2020).
ChiCTR2000030256 {published data only}
    1. ChiCTR2000030256. Epidemiological and clinical characteristics of COVID-19: a large-scale investigation in epicenter Wuhan, China. www.chictr.org.cn/showproj.aspx?proj=50078 (first received 27 April 2020).
ChiCTR2000030327 {published data only}
    1. ChiCTR2000030327. Analysis of clinical characteristics of novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showproj.aspx?proj=50214 (first received 27 April 2020).
ChiCTR2000030363 {published data only}
    1. ChiCTR2000030363. Novel coronavirus infected disease (COVID-19) in children: epidemiology, clinical features and treatment outcome. www.chictr.org.cn/showproj.aspx?proj=49984 (first received 27 April 2020).
ChiCTR2000030387 {published data only}
    1. ChiCTR2000030387. Clinical observation and research of multiple organs injury in severe patients with novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showproj.aspx?proj=50329 (first received 27 April 2020).
ChiCTR2000030464 {published data only}
    1. ChiCTR2000030464. Study for the clinical characteristics of novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showproj.aspx?proj=50382 (first received 27 April 2020).
ChiCTR2000030491 {published data only}
    1. ChiCTR2000030491. A medical records based study for comparing differences of clinical features and outcomes of novel coronavirus pneumonia (COVID-19) patients between Sichuan Province and Wuhan City. www.chictr.org.cn/hvshowproject.aspx?id=23102 (first received 27 April 2020).
ChiCTR2000030519 {published data only}
    1. ChiCTR2000030519. Study for the clinical characteristics and digestive system damage of novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showproj.aspx?proj=50604 (first received 27 April 2020).
ChiCTR2000030544 {published data only}
    1. ChiCTR2000030544. Study for the risk factors of critically ill patients with novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showproj.aspx?proj=50134 (first received 27 April 2020).
ChiCTR 2000030679 {published data only}
    1. ChiCTR 2000030679. Cohort study of novel coronavirus infected diseases (COVID-19) in children. www.chictr.org.cn/hvshowproject.aspx?id=23417 (first received 27 April 2020).
ChiCTR2000030707 {published data only}
    1. ChiCTR2000030707. Retrospective study on novel coronavirus pneumonia (COVID-19) in Tibetan Plateau. www.chictr.org.cn/showproj.aspx?proj=50160 (first received 27 April 2020).
ChiCTR2000030722 {published data only}
    1. ChiCTR2000030722. Auscultatory characteristics of novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showproj.aspx?proj=50338 (first received 27 April 2020).
ChiCTR2000030739 {published data only}
    1. ChiCTR2000030739. Exploration of the clinical characteristics of patients with novel coronavirus pneumonia (COVID-19) and its differences from patients with severe influenza A and MERS. www.chictr.org.cn/showproj.aspx?proj=50896 (first received 27 April 2020).
ChiCTR2000030755 {published data only}
    1. ChiCTR2000030755. A medical records based study for characteristics, prognosis of elderly patients with novel coronavirus pneumonia (COVID-19) in Wuhan area. www.chictr.org.cn/hvshowproject.aspx?id=23554 (first received 27 April 2020).
ChiCTR2000030778 {published data only}
    1. ChiCTR2000030778. A medical records based study for epidemic and clinical features of novel coronavirus pneumonia (COVID-19) in Ningbo First Hospital. www.chictr.org.cn/hvshowproject.aspx?id=23642 (first received 27 April 2020).
ChiCTR2000030784 {published data only}
    1. ChiCTR2000030784. A study for clinical characteristics of novel coronavirus pneumonia (COVID-19) patients follow-up in Guangxi. www.chictr.org.cn/showproj.aspx?proj=50307 (first received 27 April 2020).
ChiCTR2000030796 {published data only}
    1. ChiCTR2000030796. Clinical characteristics and treatment of novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showproj.aspx?proj=50991 (first received 27 April 2020).
ChiCTR 2000030798 {published data only}
    1. ChiCTR 2000030798. A medical records based study for clinical characteristics of novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/hvshowproject.aspx?id=23687 (first received 27 April 2020).
ChiCTR2000030803 {published data only}
    1. ChiCTR2000030803. Collection and analysis of clinical data in severe and critically ill patients with novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showproj.aspx?proj=51007 (first received 27 April 2020).
ChiCTR2000030807 {published data only}
    1. ChiCTR2000030807. Clinical characteristics and prognosis of cancer patients with novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showproj.aspx?proj=51019 (first received 27 April 2020).
ChiCTR2000030818 {unpublished data only}
    1. ChiCTR2000030818. A medical records based study for the value of Lymphocyte subsets in the diagnose and treatment. www.chictr.org.cn/hvshowproject.aspx?id=23742 (first received 27 April 2020).
ChiCTR2000030819 {published data only (unpublished sought but not used)}
    1. ChiCTR2000030819. Retrospective analysis of digestive system symptoms in 600 cases of novel coronavirus pneumonia (COVID-19) in Guanggu district, Wuhan. www.chictr.org.cn/showproj.aspx?proj=51039 2020.
ChiCTR2000030834 {published data only}
    1. ChiCTR2000030834. Epidemiological characteristics and antibody levels of novel coronavirus pneumonia (COVID-19) of pediatric medical staff working in quarantine area. www.chictr.org.cn/showproj.aspx?proj=51047 (frist received 27 April 2020).
ChiCTR2000030854 {published data only}
    1. ChiCTR2000030854. A clinical multicenter study for the occurrence, development and prognosis of novel coronavirus pneumonia (COVID-19). www.chictr.org.cn/showprojen.aspx?proj=51083 (first received 27 April 2020).
ChiCTR2000030858 {published data only}
    1. ChiCTR2000030858. Clinical characteristics and outcomes of 483 mild patients with novel coronavirus pneumonia (COVID-19) in Wuhan, China during the outbreak: a single-center, retrospective study from the mobile cabin hospital. www.chictr.org.cn/showproj.aspx?proj=51097 (first received 27 April 2020).
ChiCTR2000030863 {published data only}
    1. ChiCTR2000030863. Clinical and CT imaging characteristics of novel coronavirus pneumonia (COVID-19): an multicenter cohort study. www.chictr.org.cn/showproj.aspx?proj=50767 (first received 27 April 2020).
NCT04270383 {published data only}
    1. NCT04270383. Clinical characteristics and long-term prognosis of 2019-nCoV infection in children. clinicaltrials.gov/ct2/show/NCT04270383 (first received 17 February 2020).
NCT04279782 {published data only}
    1. NCT04279782. Clinical features of suspected and confirmed patients of 2019 novel coronavirus infection. www.clinicaltrials.gov/ct2/show/NCT04279782 (first received 27 April 2020).
NCT04279899 {published data only}
    1. NCT04279899. The investigation of the neonates with or with risk of COVID-19. clinicaltrials.gov/ct2/show/NCT04279899 (first received 27 April 2020).
NCT04285801 {published data only}
    1. NCT04285801. Critically ill patients with COVID-19 in Hong Kong: a multicentre observational cohort study. clinicaltrials.gov/ct2/show/NCT04285801 (first received 27 April 2020).
NCT04292327 {published data only}
    1. NCT04292327. Clinical progressive characteristics and treatment effects of 2019-novel coronavirus. clinicaltrials.gov/ct2/show/NCT04292327 (first received 27 April 2020).
NCT04292964 {published data only}
    1. NCT04292964. Prognostic factors of patients with COVID-19. clinicaltrials.gov/ct2/show/NCT04292964 (first received 27 April 2020).
NCT04315870 {published data only}
    1. NCT04315870. Clinical characteristics of coronavirus disease 2019 (COVID-19) in pregnancy: the Italian Registry on coronavirus in pregnancy. clinicaltrials.gov/ct2/show/NCT04315870 (first received 20 March 2020).

Additional references

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References to other published versions of this review

Deeks 2020b
    1. Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Leeflang MM, Spijker R, et al. Diagnosis of SARS-CoV-2 infection and COVID-19: accuracy of signs and symptoms; molecular, antigen, and antibody tests; and routine laboratory markers. Cochrane Database of Systematic Reviews 2020, Issue 4. Art. No: CD013596. [DOI: 10.1002/14651858.CD013596] - DOI
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