Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

Flook, M.; Jackson, C.; Vasileiou, E.; Simpson, C. R.; Muckian, M. D.; Agrawal, U.; McCowan, C.; Jia, Y.; Murray, J. L. K.; Ritchie, L. D.; Robertson, C.; Stock, S. J.; Wang, X.; Woolhouse, M. E. J.; Sheikh, A.; Stagg, H. R.

doi:10.1186/s12879-021-05992-1

Table 2 Included studies

From: Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

Author	Type of study	Country	Study population	Overall number of patients	Analytical method used	Factors included in multivariable model	Disease, disease severity, or death	Definition of severity
Cai [19]	Retrospective cohort	China	Hospitalised patients, single hospital	298	Univariable; logistic regression	N/A; age, sex, comorbidities, clinical markers, travel history	Disease severity	As per the international guidelines for community-acquired pneumonia, with a scoring system based on demographics, comorbid illness, physical examination findings, and laboratory and radiographic findings
Chen [20]	Retrospective cohort	China	Hospitalised patients, single hospital	249	Logistic regression	Age, sex, comorbidities and a range of clinical measures	Disease severity	ICU admission
Chen [21]	Retrospective cohort with a nested case-control study	China	Hospitalised patients (moderately, severely or critically ill), single hospital	274	Univariable	N/A	Death	N/A
Chen [22]	Case-control	China	COVID-19 vs. pneumonia negative for SARS-CoV-2	104 (78 COVID-19)	Univariable	N/A	Disease	N/A
Chen [23]	Retrospective cohort	China	Hospitalised patients, single hospital	21	Univariable	N/A	Disease severity	Severe meets any of the following criteria- respiratory distress, RR ≥ 30 breaths/min; SpO₂ ≤ 93% at rest; and PaO₂/FIO₂ ≤ 300. Patients with greater than 50% lesion progression within 24 to 48 h in pulmonary imaging.
Cheng [24]	Case-control	China	Patients presenting with fever diagnosed with pneumonia by specialists with chest CT scans	38 (11 COVID-19)	Univariable	N/A	Disease	N/A
Chinese CDC [25]	Retrospective cohort	China	Nationwide surveillance	72,314	Univariable	N/A	Death	N/A
Fan [26]	Retrospective cohort	Singapore	Hospitalised patients, National Centre for Infectious Diseases	67	Univariable	N/A	Disease severity	ICU admission
Grasselli [27]	Prospective cohort with a nested case-control study	Italy	Hospitalised in ICU across 72 hospitals	1591	Univariable	N/A	Death	N/A
Han [28]	Retrospective cohort	China	Hospitalised patients, single hospital	273	Univariable	N/A	Disease severity	Severe met at least one of the following conditions: a) shortness of breath, RR ≥ 30 times/min, b) oxygen saturation (resting state) ≤93%, or c) PaO₂/FiO₂ ≤ 300 mmHg., in addition to positive SARS-CoV-2 RNA nucleic acid test by Reverse transcription polymerase chain reaction, fever, or other respiratory symptoms (the typical CT image abnormities of viral pneumonia were optional). Critical patients also needed to meet at least one of the extra following conditions: a) respiratory failure that needs to receive mechanical ventilation; b) shock; and c) multiple organ failure that need to be transferred to the ICU.
Huang [29]	Retrospective cohort	China	Hospitalised patients, single hospital	41	Univariable	N/A	Disease severity	ICU admission
ICNARC [30]	Case-control (disease) / Prospective cohort (disease severity)	England, Northern Ireland and Wales	Hospitalised patients in ICU across a network of hospitals	12,502 (6720 COVID-19)	Univariable	N/A	Disease; Disease severity	Receiving advanced, as opposed to basic, respiratory support
Liang [31]	Prospective cohort	China	Hospitalised patients across 575 hospitals	1590	Logistic regression; Cox regression	Logistic model adjusted for age, sex, smoking history, comorbidities, cancer	Disease severity, Death	Invasive ventilation, ICU admission, death
Liu [32]	Retrospective cohort	China	Hospitalised patients, single hospital	119	Univariable	N/A	Disease severity	Severe- dyspnoea accompanied by hypoxemia, sometimes acute respiratory distress syndrome, septic shock and multiple organ failure
Liu [33]	Retrospective cohort	China	Hospitalised patients, single hospital	4880	Logistic regression	Age, sex	Disease	N/A
Qiu [34]	Retrospective cohort	China	Hospitalised paediatric patients, three hospitals	36	Univariable	N/A	Disease severity	Moderate disease (mild was baseline)- mild pneumonia; symptoms such as fever, cough, fatigue, headache, and myalgia; no complications and manifestations related to severe conditions
Ruan [35]	Retrospective cohort with a nested case-control study	China	Hospitalised patients across two hospitals with a definitive outcome	150	Univariable	N/A	Death	N/A
Shi [36]	Retrospective cohort	China	Hospitalised patients across a province	487	Univariable; logistic regression	N/A; age, sex, hypertension; full list unknown	Disease severity	Severe pneumonia, characterised by fever, cough, dyspnoea, bilateral pulmonary infiltrates, and acute respiratory injury
Simmonet [37]	Retrospective cohort	France	Hospitalised patients in ICU, single hospital	124	Logistic regression	Age, sex, diabetes, hypertension, BMI	Disease severity	Receiving invasive mechanical ventilation, determined when oxygen therapy (≥ 10 L/min) with target SpO₂ (90–94%) was ineffective, and when RR was above 25/min, with signs of acute respiratory failure, despite maximal oxygen therapy
Tian [38]	Retrospective cohort	China	Hospitalised individuals transferred from the hospitals of Beijing to the designated hospitals for specialist treatment of infectious diseases by Beijing Emergency Medical Service	262	Univariable	N/A	Disease severity	Severe- dyspnoea or respiratory failure in addition to fever, respiratory symptoms and radiographic evidence of pneumonia
Wan [39]	Prospective cohort	China	Hospitalised patients, single hospital	135	Univariable	N/A	Disease severity	Severe group- respiratory distress, RR ≥ 30 breaths/minute in a resting state, a mean oxygen saturation of ≤93%, and an PaO₂/FiO₂ ≤ 300 mmHg
Wang [40]	Case-control	China	Country-wide data compared to historic SARS/MERS	11,425 (835 COVID-19)	Univariable	N/A	Disease	N/A
Wang [41]	Retrospective cohort	China	Hospitalised patients, single hospital	138	Univariable	N/A	Disease severity	ICU admission
Wang [42]	Prospective cohort	China	Hospitalised patients, single hospital	116	Univariable	N/A	Disease severity	Severe- fever or suspected respiratory infection, plus one of the following: RR > 30 breaths/min; severe respiratory distress; or SpO₂ ≤ 93% on room air
Wang [43]	Cross-sectional	China	Hospitalised patients, single hospital	69	Univariable	N/A	Disease severity	SpO₂ < 90%
Wu [44]	Retrospective cohort	China	Hospitalised patients, single hospital	201	Univariable; Cox regression	N/A	Disease severity, Death	ARDS, mechanical ventilation
Wu [45]	Prospective cohort	China	Country-wide data	44,672	Univariable	N/A	Death	N/A
Yang [46]	Retrospective cohort	China	Hospitalised patients, single hospital, admitted to ICU	52	Univariable; Cox regression	N/A	Death	N/A
Yuan [47]	Retrospective cohort	China	Hospitalised patients, single hospital	27	Univariable	N/A	Death	N/A
Zhang [48]	Retrospective cohort	China	Hospitalised patients, single hospital	140	Univariable	N/A	Disease severity	Severe COVID-19 was designated when the patients had one of the following criteria: (a) respiratory distress with respiratory frequency ≥ 30/min; (b) pulse oximeter oxygen saturation ≤ 93% at rest; and (c) oxygenation index (PaO₂/FiO₂) ≤ 300 mmHg.
Zhang [49]	Retrospective cohort	China	Hospitalised patients (patients with no severe underlying diseases), single hospital	95	Univariable	N/A	Disease severity	Severe- RR ≥ 30 times / min; at rest, oxygen saturation ≤ 93%; PaO₂/FiO₂ ≤ 300 mmHg
Zhang [50]	Retrospective cohort	China	Hospitalised patients, single hospital	120	Univariable	N/A	Disease severity	Severe- when patients met one of the following criteria: (1) respiratory distress with a breathing rate ≥ 30/min; (2) pulse oximeter oxygen saturation ≤ 93% at rest; (3) oxygenation index (PaO₂/FiO₂) ≤300 mmHg; (4) respiratory failure requiring mechanical ventilation; (5) shock; and (6) combined with other organ failure requiring ICU monitoring and treatment
Zhou [51]	Retrospective cohort with a nested case-control study	China	Hospitalised patients across two hospitals with a definitive outcome	191	Univariable; logistic regression	N/A; age, coronary heart disease, Sequential Organ Failure Assessment score, lymphocyte count, D-dimer	Death	N/A

ARDS acute respiratory distress syndrome, BMI body mass index, CDC Center for Disease Control and Prevention, CT computed tomography, FiO₂ inspired oxygen fraction, ICNARC intensive care national audit and research centre, ICU intensive care unit, MERS Middle Eastern Respiratory Syndrome, N/A not applicable, PaO₂ arterial partial pressure of oxygen, RR respiratory rate, SARS severe acute respiratory syndrome, SpO₂ oxygen saturation

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ISSN: 1471-2334

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