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Exercise for COVID-19: real-time meta analysis of 48 studies
Covid Analysis, December 2022
https://c19early.org/exmeta.html
 
0 0.5 1 1.5+ All studies 38% 48 1,732,155 Improvement, Studies, Patients Relative Risk Mortality 44% 14 1,442,623 Ventilation 46% 2 43,773 ICU admission 41% 4 708,149 Hospitalization 34% 15 853,243 Cases 20% 18 194,079 Peer-reviewed 36% 46 1,727,287 Exercise for COVID-19 c19early.org/ex Dec 2022 Favorsexercise Favorsinactivity after exclusions
Statistically significant improvements are seen for mortality, ventilation, ICU admission, hospitalization, progression, recovery, and cases. 34 studies from 34 independent teams in 18 different countries show statistically significant improvements in isolation (26 for the most serious outcome).
Meta analysis using the most serious outcome reported shows 38% [30‑44%] improvement. Results are similar after exclusions and similar for peer-reviewed studies.
Results are robust — in exclusion sensitivity analysis 35 of 48 studies must be excluded to avoid finding statistically significant efficacy in pooled analysis.
Results are consistent with the overall risk of all cause mortality based on cardiorespiratory fitness — [Laukkanen] show RR 0.55 [0.50-0.61] for the top vs. bottom tertiles.
0 0.5 1 1.5+ All studies 38% 48 1,732,155 Improvement, Studies, Patients Relative Risk Mortality 44% 14 1,442,623 Ventilation 46% 2 43,773 ICU admission 41% 4 708,149 Hospitalization 34% 15 853,243 Cases 20% 18 194,079 Peer-reviewed 36% 46 1,727,287 Exercise for COVID-19 c19early.org/ex Dec 2022 Favorsexercise Favorsinactivity after exclusions
Studies analyze exercise/physical activity levels before infection, comparing regular/moderate exercise vs. lower/no exercise. Risk may increase with more extreme activity levels.
No treatment, vaccine, or intervention is 100% effective and available. All practical, effective, and safe means should be used based on risk/benefit analysis.
All data to reproduce this paper and sources are in the appendix. Other meta analyses for exercise can be found in [Ezzatvar, Li, Rahmati, Sittichai], showing significant improvements for mortality, ICU admission, hospitalization, severity, and cases.
Highlights
Exercise reduces risk for COVID-19 with very high confidence for mortality, ICU admission, hospitalization, cases, and in pooled analysis, and low confidence for ventilation, progression, and recovery.
We show traditional outcome specific analyses and combined evidence from all studies.
Real-time updates and corrections, transparent analysis with all results in the same format, consistent protocol for 47 treatments.
A
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Hamer 28% 0.72 [0.61-0.87] hosp. n/a n/a Improvement, RR [CI] Treatment Control Brawner 74% 0.26 [0.11-0.58] hosp. n/a n/a Tret'yakov 98% 0.02 [0.00-0.27] severe case 0/27 53/266 Gao -105% 2.05 [1.39-3.02] cases case control Ho 35% 0.65 [0.48-0.89] hosp. 213/123,588 59/14,887 Halabchi 89% 0.11 [0.01-1.46] death 0/249 79/4,445 Zhang 26% 0.74 [0.48-1.14] death n/a n/a Li 81% 0.19 [0.05-0.74] severe case n/a n/a per SD increase Tavakol 69% 0.31 [0.10-1.02] severe case 3/64 19/124 Yates 45% 0.55 [0.38-0.79] death 72/163,912 62/30,119 Holt 17% 0.83 [0.63-1.09] cases n/a n/a Cho 53% 0.47 [0.26-0.87] death case control Sallis 59% 0.41 [0.22-0.76] death 11/3,118 170/6,984 Christensen 63% 0.37 [0.16-0.85] death 543 (n) 529 (n) Latorre-Román 76% 0.24 [0.05-1.04] hosp. n/a n/a Marcus 42% 0.58 [0.48-0.71] symp. case 240/10,627 134/3,708 Yuan 91% 0.09 [0.01-1.65] death 0/61 6/103 Brandenburg -6% 1.06 [0.23-4.79] hosp. 102 (n) 39 (n) Bielik 30% 0.70 [0.40-1.21] mod. case 775 (n) 365 (n) af Geijerstam 50% 0.50 [0.31-0.81] death 318,902 (n) 336,271 (n) Lee 74% 0.26 [0.07-0.99] death 2/11,072 32/41,293 Maltagliati 52% 0.48 [0.25-0.87] hosp. n/a n/a Baynouna AlKetbi 98% 0.01 [0.00-0.44] death n/a n/a Ahmadi 30% 0.70 [0.54-0.89] death 160/232,613 112/95,221 Nguyen 20% 0.80 [0.72-0.88] symp. case 904/2,836 483/1,111 Lin 47% 0.53 [0.12-2.33] cases n/a n/a de Souza 73% 0.27 [0.07-1.06] ventilation 3/611 6/327 Mohsin 19% 0.81 [0.66-0.99] severe case 86/258 224/544 Ekblom-Bak 48% 0.52 [0.30-0.92] severe case n/a n/a Lengelé 74% 0.26 [0.07-0.80] cases 23/229 4/12 Saadeh 9% 0.91 [0.56-1.43] symp. case 362 (n) 225 (n) Hamrouni 29% 0.71 [0.55-0.92] death 138/106,006 109/47,827 Huang 47% 0.53 [0.23-1.22] severe case 7/74 16/90 Hamdan 16% 0.84 [0.49-1.39] hosp. 22/128 37/172 Steenkamp 42% 0.58 [0.50-0.68] death 29,469 (n) 13,366 (n) Gilley -42% 1.42 [0.60-3.35] cases 172/1,917 5/79 Almansour 6% 0.94 [0.40-1.47] cases 35/71 38/71 Beydoun 43% 0.57 [0.32-1.01] cases 1,710 (n) 448 (n) Salgado-Aranda 83% 0.17 [0.05-0.56] death 4/223 41/297 Paul 38% 0.62 [0.30-1.20] no recov. n/a n/a Kontopoulou 66% 0.34 [0.24-0.47] recov. time 42 (n) 24 (n) Malisoux 63% 0.37 [0.14-0.98] progression 115 (n) 108 (n) Antunes 80% 0.20 [0.03-1.41] ICU 1/14 9/25 Tsuzuki 56% 0.44 [0.36-0.52] severe case 3,340 (n) 1,528 (n) Reis 41% 0.59 [0.26-1.26] hosp. 9/241 29/305 Pływaczewska-J.. 11% 0.89 [0.72-1.11] m/s case 490 (n) 1,357 (n) Pitanga 33% 0.67 [0.45-1.01] cases 1,469 (n) 1,552 (n) Green 42% 0.58 [0.53-0.63] cases 1,267/11,144 16,198/101,931 Tau​2 = 0.07, I​2 = 79.4%, p < 0.0001 Prophylaxis 38% 0.62 [0.56-0.70] 3,372/1,026,402 17,925/705,753 38% improvement All studies 38% 0.62 [0.56-0.70] 3,372/1,026,402 17,925/705,753 38% improvement 48 exercise COVID-19 studies c19early.org/ex Dec 2022 Tau​2 = 0.07, I​2 = 79.4%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) Favors exercise Favors inactivity
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Hamer 28% hospitalization Relative Risk [CI] Brawner 74% hospitalization Tret'yakov 98% severe case Gao -105% case Ho 35% hospitalization Halabchi 89% death Zhang 26% death Li 81% severe case per SD increase Tavakol 69% severe case Yates 45% death Holt 17% case Cho 53% death Sallis 59% death Christensen 63% death Latorre-Román 76% hospitalization Marcus 42% symp. case Yuan 91% death Brandenburg -6% hospitalization Bielik 30% mod. case af Geijerstam 50% death Lee 74% death Maltagliati 52% hospitalization Baynouna AlKetbi 98% death Ahmadi 30% death Nguyen 20% symp. case Lin 47% case de Souza 73% ventilation Mohsin 19% severe case Ekblom-Bak 48% severe case Lengelé 74% case Saadeh 9% symp. case Hamrouni 29% death Huang 47% severe case Hamdan 16% hospitalization Steenkamp 42% death Gilley -42% case Almansour 6% case Beydoun 43% case Salgado-Aranda 83% death Paul 38% recovery Kontopoulou 66% recovery Malisoux 63% progression Antunes 80% ICU admission Tsuzuki 56% severe case Reis 41% hospitalization Pływaczewska-.. 11% mod./sev. case Pitanga 33% case Green 42% case Tau​2 = 0.07, I​2 = 79.4%, p < 0.0001 Prophylaxis 38% 38% improvement All studies 38% 38% improvement 48 exercise COVID-19 studies c19early.org/ex Dec 2022 Tau​2 = 0.07, I​2 = 79.4%, p < 0.0001 Effect extraction pre-specifiedRotate device for details Favors exercise Favors inactivity
B
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C
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D
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Figure 1. A. Random effects meta-analysis. This plot shows pooled effects, see the specific outcome analyses for individual outcomes, and the heterogeneity section for discussion. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix. B. Scatter plot showing the most serious outcome in all studies. The diamond shows the results of random effects meta-analysis. C. Results within the context of multiple COVID-19 treatments. D. Timeline of results in exercise studies.
We analyze all significant studies reporting COVID-19 outcomes as a function of physical activity levels. Search methods, inclusion criteria, effect extraction criteria (more serious outcomes have priority), all individual study data, PRISMA answers, and statistical methods are detailed in Appendix 1. We present random effects meta-analysis results for all studies, for studies within each treatment stage, for individual outcomes, for peer-reviewed studies, for Randomized Controlled Trials (RCTs), and after exclusions.
Insufficient physical activity is a risk factor for many diseases and is common around the world [Guthold], as shown in Figure 2. [Guthold] found that prevalence in high-income countries was over twice as high, and has increased over time.
Figure 2. Low physical activity levels are common. Prevalence of insufficient physical activity around the world as of 2016, from [Guthold] (top: female, bottom: male).
For upper respiratory tract infections, research shows lower risk for moderate activity vs. a sedentary lifestyle, however risk may increase with more extreme activity levels [Nieman].
Table 1 summarizes the results for all studies, with different exclusions, and for specific outcomes. Figure 3, 4, 5, 6, 7, 8, 9, 10, and 11 show forest plots for random effects meta-analysis of all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, progression, recovery, cases, and peer reviewed studies.
Improvement Studies Patients Authors
All studies38% [30‑44%]48 1,732,155 450
After exclusions36% [28‑42%]44 1,730,830 418
Peer-reviewed studiesPeer-reviewed36% [29‑43%]46 1,727,287 444
Mortality44% [34‑53%]14 1,442,623 140
VentilationVent.46% [32‑57%]2 43,773 18
ICU admissionICU41% [35‑47%]4 708,149 32
HospitalizationHosp.34% [25‑42%]15 853,243 109
Cases20% [7‑31%]18 194,079 223
Table 1. Random effects meta-analysis for all studies, with different exclusions, and for specific outcomes. Results show the percentage improvement with increased activity levels and the 95% confidence interval.
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Figure 3. Random effects meta-analysis for all studies with pooled effects. This plot shows pooled effects, see the specific outcome analyses for individual outcomes, and the heterogeneity section for discussion. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix.
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Figure 4. Random effects meta-analysis for mortality results.
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Figure 5. Random effects meta-analysis for ventilation.
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Figure 6. Random effects meta-analysis for ICU admission.
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Figure 7. Random effects meta-analysis for hospitalization.
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Figure 8. Random effects meta-analysis for progression.
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Figure 9. Random effects meta-analysis for recovery.
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Figure 10. Random effects meta-analysis for cases.
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Figure 11. Random effects meta-analysis for peer reviewed studies. [Zeraatkar] analyze 356 COVID-19 trials, finding no significant evidence that peer-reviewed studies are more trustworthy. They also show extremely slow review times during the pandemic. Authors recommend using preprint evidence, with appropriate checks for potential falsified data, which provides higher certainty much earlier. Effect extraction is pre-specified, using the most serious outcome reported, see the appendix for details.
To avoid bias in the selection of studies, we analyze all non-retracted studies. Here we show the results after excluding studies with major issues likely to alter results, non-standard studies, and studies where very minimal detail is currently available. Our bias evaluation is based on analysis of each study and identifying when there is a significant chance that limitations will substantially change the outcome of the study. We believe this can be more valuable than checklist-based approaches such as Cochrane GRADE, which may underemphasize serious issues not captured in the checklists, overemphasize issues unlikely to alter outcomes in specific cases (for example, lack of blinding for an objective mortality outcome, or certain specifics of randomization with a very large effect size), or be easily influenced by potential bias. However, they can also be very high quality.
The studies excluded are as below. Figure 12 shows a forest plot for random effects meta-analysis of all studies after exclusions.
[Brawner], unadjusted results with no group details.
[de Souza], unadjusted results with no group details. Excluded results: mechanical ventilation.
[Huang], unadjusted results with no group details. Excluded results: severe case.
[Kontopoulou], unadjusted results with no group details.
[Mohsin], unadjusted results with no group details.
[Tret'yakov], unadjusted results with no group details.
[Yuan], excessive unadjusted differences between groups. Excluded results: death.
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Figure 12. Random effects meta-analysis for all studies after exclusions. This plot shows pooled effects, see the specific outcome analyses for individual outcomes, and the heterogeneity section for discussion. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix.
More physically active people have reduced risk for COVID-19. Statistically significant improvements are seen for mortality, ventilation, ICU admission, hospitalization, progression, recovery, and cases. 34 studies from 34 independent teams in 18 different countries show statistically significant improvements in isolation (26 for the most serious outcome). Meta analysis using the most serious outcome reported shows 38% [30‑44%] improvement. Results are similar after exclusions and similar for peer-reviewed studies. Results are robust — in exclusion sensitivity analysis 35 of 48 studies must be excluded to avoid finding statistically significant efficacy in pooled analysis. Results are consistent with the overall risk of all cause mortality based on cardiorespiratory fitness — [Laukkanen] show RR 0.55 [0.50-0.61] for the top vs. bottom tertiles.
Studies analyze exercise/physical activity levels before infection, comparing regular/moderate exercise vs. lower/no exercise. Risk may increase with more extreme activity levels.
0 0.5 1 1.5 2+ Mortality 50% Improvement Relative Risk ICU admission 40% Hospitalization 27% c19early.org/ex af Geijerstam et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[af Geijerstam] Prospective study of 1,559,187 men in Sweden with cardiorespiratory fitness levels measured on military conscription, showing high cardiorespiratory fitness associated with lower risk of COVID-19 hospitalization, ICU admission, and death.
0 0.5 1 1.5 2+ Mortality 30% Improvement Relative Risk c19early.org/ex Ahmadi et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Ahmadi] Retrospective 468,569 adults in the UK, showing no significant difference in COVID-19 mortality based on diet quality, however significantly lower mortality was seen with higher diet quality for pneumonia and infectious diseases.
0 0.5 1 1.5 2+ Case 6% Improvement Relative Risk c19early.org/ex Almansour et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Almansour] Retrospective 142 patients in Saudi Arabia, showing no significant difference in cases with physical activity.
0 0.5 1 1.5 2+ ICU admission 80% Improvement Relative Risk CT >50% 40% CT 25-50% 73% Hospitalization time 43% Disease duration 26% c19early.org/ex Antunes et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Antunes] Retrospective 39 hospitalized COVID-19 survivors >60 years old, showing shorter hospitalization for patients with active lifestyles before COVID-19 symptoms.
0 0.5 1 1.5 2+ Mortality 98% Improvement Relative Risk c19early.org/ex Baynouna AlKetbi et al. Exercise Prophylaxis Favors exercise Favors inactivity
[Baynouna AlKetbi] Retrospective 234 COVID-19 cases in the United Arab Emirates, showing lower risk of mortality with increased physical activity.
0 0.5 1 1.5 2+ Case, >1/week vs. none 43% Improvement Relative Risk Case, 1-4/mon vs. none 62% c19early.org/ex Beydoun et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Beydoun] Retrospective 2,830 people in the USA, showing lower risk of COVID-19 with a history of moderate/vigorous exercise.
0 0.5 1 1.5 2+ Moderate case 30% Improvement Relative Risk Case -9% c19early.org/ex Bielik et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Bielik] Retrospective 1,544 participants in Slovakia, showing a lower risk of more severe COVID-19 for physically active participants, without statistical significance.
0 0.5 1 1.5 2+ Hospitalization, PA -6% Improvement Relative Risk Hospitalization, CRF 78% Hospitalization, CRF (b) 64% Severe case, PA 35% Severe case, CRF 24% c19early.org/ex Brandenburg et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Brandenburg] Retrospective 263 COVID+ patients, showing lower hospitalization with higher self-reported cardiorespiratory fitness, but no significant differences for physical activity. Participants in the study were healthier and more fit than the general population.
0 0.5 1 1.5 2+ Hospitalization 74% unadjusted Improvement Relative Risk c19early.org/ex Brawner et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Brawner] Retrospective 246 COVID-19 patients in the USA, showing the risk of hospitalization inversely associated with maximal exercise capacity. Adjusted results are only provided for MET as a continuous variable.
0 0.5 1 1.5 2+ Mortality 53% Improvement Relative Risk Case 10% c19early.org/ex Cho et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Cho] Retrospective 6,288 COVID+ patients and 125,772 matched controls in South Korea, showing significantly lower risk of COVID-19 infection and mortality with higher physical activity.
0 0.5 1 1.5 2+ Mortality 63% Improvement Relative Risk Case 23% c19early.org/ex Christensen et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Christensen] Prospective study of 2,690 adults in the UK Biobank showing lower cardiorespiritory fitness associated with COVID-19 mortality.
0 0.5 1 1.5 2+ Ventilation 73% unadjusted Improvement Relative Risk Hospitalization 34% c19early.org/ex de Souza et al. NCT04396353 Exercise Prophylaxis Favors exercise Favors inactivity
[de Souza] Retrospective survey of 938 COVID-19 recovered patients in Brazil, showing lower hospitalization with physical activity. NCT04396353.
0 0.5 1 1.5 2+ Severe case 48% Improvement Relative Risk c19early.org/ex Ekblom-Bak et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Ekblom-Bak] Retrospective 857 severe COVID-19 cases and matched controls in Sweden, showing lower risk of severe COVID-19 with higher cardiorespiratory fitness.
0 0.5 1 1.5 2+ Case -105% Improvement Relative Risk c19early.org/ex Gao et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Gao] Case control study in China with 105 cases and 210 matched controls, showing COVID-19 cases associated with physical activity ≥5 times per week. Authors note that people may choose gyms for exercise in winter, leading to higher exposure risk.
0 0.5 1 1.5 2+ Case -42% unadjusted Improvement Relative Risk c19early.org/ex Gilley et al. NCT04766788 Exercise Prophylaxis Favors exercise Favors inactivity
[Gilley] Retrospective survey of 1,997 college students in the USA, showing no significant difference in COVID-19 cases with exercise in unadjusted results.
0 0.5 1 1.5 2+ Case 42% Improvement Relative Risk c19early.org/ex Green et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Green] Retrospective 113,075 people in Israel, showing lower risk of COVID-19 cases with physical activity and a dose dependent response.
0 0.5 1 1.5 2+ Mortality 89% Improvement Relative Risk Hospitalization 28% c19early.org/ex Halabchi et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Halabchi] Retrospective 4,694 COVID-19 patients in Iran, showing lower risk of hospitalization and mortality with regular sports participation.
0 0.5 1 1.5 2+ Hospitalization 16% Improvement Relative Risk c19early.org/ex Hamdan et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Hamdan] Retrospective 300 participants in Palestine, showing lower risk of hospitalization with physical activity, without statistical significance.
0 0.5 1 1.5 2+ Hospitalization 28% Improvement Relative Risk Hospitalization (b) 34% c19early.org/ex Hamer et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Hamer] UK Biobank retrospective analysis of 387,109 people, showing lower risk of COVID-19 hospitalization with physical activity.
0 0.5 1 1.5 2+ Mortality 29% Improvement Relative Risk c19early.org/ex Hamrouni et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Hamrouni] Prospective UK Biobank analysis, showing a history of low physical activity associated with COVID-19 mortality.
0 0.5 1 1.5 2+ Hospitalization 35% Improvement Relative Risk c19early.org/ex Ho et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Ho] UK Biobank retrospective 235,928 participants using walking pace as a proxy for physical fitness, showing lower risk of COVID-19 hospitalization with an average vs. slow walking pace.
0 0.5 1 1.5 2+ Case 17% Improvement Relative Risk c19early.org/ex Holt et al. NCT04330599 COVIDENCE UK Exercise Prophylaxis Favors exercise Favors inactivity
[Holt] Prospective survey-based study with 15,227 people in the UK, showing reduced risk of COVID-19 cases with lower impact physical activity. NCT04330599. COVIDENCE UK.
0 0.5 1 1.5 2+ Severe case 47% unadjusted Improvement Relative Risk Severe case (b) 8% unadjusted Case 66% c19early.org/ex Huang et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Huang] Retrospective 164 COVID-19 patients and 188 controls in China, showing lower risk of cases with regular exercise.
0 0.5 1 1.5 2+ Recovery time 66% Improvement Relative Risk Dyspnea after hospitalizat.. 67% c19early.org/ex Kontopoulou et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Kontopoulou] Retrospective 66 hospitalized COVID-19 patients in Greece, showing significantly improved recovery with a history of exercise in unadjusted results. Exercise after hospitalization was also associated with lower levels of dyspnea one month post hospitalization.
0 0.5 1 1.5 2+ Hospitalization 76% Improvement Relative Risk Hospitalization (b) 87% c19early.org/ex Latorre-Román et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Latorre-Román] Retrospective 420 people in Spain, showing lower risk of COVID-19 hospitalization with a history of physical activity.
0 0.5 1 1.5 2+ Mortality 74% Improvement Relative Risk Severe case 58% Case 16% c19early.org/ex Lee et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Lee] Retrospective 212,768 adults in South Korea, showing lower risk of COVID-19 cases, severity, and mortality with physical activity. Notably, results for aerobic and muscle strengthening activities combined were much better than results for either one in isolation.
0 0.5 1 1.5 2+ Case 74% Improvement Relative Risk c19early.org/ex Lengelé et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Lengelé] Analysis of 241 adults >65yo in Belgium, showing lower risk of COVID-19 with a history of physical activity.
0 0.5 1 1.5 2+ Severe case 81% Improvement Relative Risk Hospitalization 56% c19early.org/ex Li et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Li (B)] Mendelian randomization study showing lower risk of severe COVID-19 with physical activity.
0 0.5 1 1.5 2+ Case 47% Improvement Relative Risk c19early.org/ex Lin et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Lin] Prospective survey analysis of 28,575 people in 99 countries, showing a lower risk of COVID-19 with a exercise, without statistical signifcance.
0 0.5 1 1.5 2+ Progression 63% Improvement Relative Risk Progression (b) 52% Progression (c) 43% c19early.org/ex Malisoux et al. NCT04380987 Exercise Prophylaxis Favors exercise Favors inactivity
[Malisoux] Retrospective 452 participants in Luxembourg, showing lower risk of moderate cases with higher physical activity.
0 0.5 1 1.5 2+ Hospitalization 52% Improvement Relative Risk c19early.org/ex Maltagliati et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Maltagliati] Retrospective 3,139 adults >50 in Europe, with 66 COVID-19 hospitalizations, showing lower risk of hospitalization with higher physical activity and with higher muscle strength. Note that model 2 includes muscle strength which is correlated with physical activity [eurapa.biomedcentral.com].
0 0.5 1 1.5 2+ Symptomatic case 42% Improvement Relative Risk c19early.org/ex Marcus et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Marcus] Prospective survey based study with 14,335 participants, showing lower risk of viral symptoms with regular exercise.
0 0.5 1 1.5 2+ Severe case 19% Improvement Relative Risk Severe case (b) -1% c19early.org/ex Mohsin et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Mohsin] Retrospective 1,500 COVID+ patients in Bangladesh, showing lower risk of severe cases with regular exercise in unadjusted results.
0 0.5 1 1.5 2+ Symptomatic case 20% Improvement Relative Risk Symptomatic case (b) 42% c19early.org/ex Nguyen et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Nguyen] Analysis of 3,947 participants in Vietnam, showing significantly lower risk of COVID-19-like symptoms with physical activity and with a healthy diet. The combination of being physically active and eating healthy reduced risk further compared to either alone. The analyzed period was Feb 14 to Mar 2, 2020, which may have been before testing was widely available.
0 0.5 1 1.5 2+ Long COVID 38% Improvement Relative Risk Long COVID (b) 4% c19early.org/ex Paul et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Paul] Retrospective 1,811 COVID-19 patients in the UK, showing lower risk of self-reported long COVID with 3+ hours of exercise per week in the month before infection, without statistical significance (p=0.16).
0 0.5 1 1.5 2+ Case 33% Improvement Relative Risk Case (b) 43% Case (c) 20% c19early.org/ex Pitanga et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Pitanga] Retrospective 4,476 participants in Brazil, showing lower risk of COVID-19 cases with a history of physical activity, statistically significant only for those following specific practices to protect against COVID-19.
0 0.5 1 1.5 2+ Moderate/severe case 11% Improvement Relative Risk PASC 14% c19early.org/ex Pływaczewska-Jakubowska et al. Exercise Prophylaxis Favors exercise Favors inactivity
[Pływaczewska-Jakubowska] Retrospective 1,847 COVID+ patients in Poland, showing no significant difference in moderate/severe cases with physical activity. Hospitalized patients were excluded.
0 0.5 1 1.5 2+ Hospitalization 41% Improvement Relative Risk c19early.org/ex Reis et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Reis] Retrospective 546 COVID+ patients in the USA, showing lower risk of hospitalization with higher frequency of strength training, without statistical significance.
0 0.5 1 1.5 2+ Symptomatic case 9% Improvement Relative Risk Symptomatic case (b) 4% c19early.org/ex Saadeh et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Saadeh] Retrospective 904 patients in Sweden, showing higher risk of COVID-19-like symptoms with poor muscle strength. Risk was slightly higher for physical inactivity, without statistical significance.
0 0.5 1 1.5 2+ Mortality 83% Improvement Relative Risk c19early.org/ex Salgado-Aranda et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Salgado-Aranda] Retrospective 520 COVID-19 patients in Spain, showing significantly lower mortality with a history of physical activity.
0 0.5 1 1.5 2+ Mortality 59% Improvement Relative Risk ICU admission 42% Hospitalization 53% c19early.org/ex Sallis et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Sallis] Retrospective 48,440 COVID-19 patients in the USA, showing significantly lower mortality, ICU admission, and hospitalization with exercise.
0 0.5 1 1.5 2+ Mortality 42% Improvement Relative Risk Ventilation 45% ICU admission 41% Hospitalization 34% c19early.org/ex Steenkamp et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Steenkamp] Retrospective 65,361 COVID-19 patients in South Africa, showing significantly lower hospitalization, ICU admission, ventilation, and mortality with exercise.
0 0.5 1 1.5 2+ Severe case 69% Improvement Relative Risk c19early.org/ex Tavakol et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Tavakol] Retrospective 206 patients in Iran, showing COVID-19 disease severity associated with lower physical activity.
0 0.5 1 1.5 2+ Severe case 98% Improvement Relative Risk c19early.org/ex Tret'yakov et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Tret'yakov] Retrospective 293 COVID+ patients in Russia, showing lower risk of severe COVID-19 for individuals who regularly practice aerobic training in unadjusted results.
0 0.5 1 1.5 2+ Severe case 56% Improvement Relative Risk c19early.org/ex Tsuzuki et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Tsuzuki] Retrospective 4,868 elderly COVID-19 patients in Japan, showing higher risk of severe cases with poor physical activity status.
0 0.5 1 1.5 2+ Mortality 45% Improvement Relative Risk Severe case 47% c19early.org/ex Yates et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Yates] UK Biobank retrospective 412,596 people, showing severe COVID-19 and COVID-19 mortality inversely associated with self-reported walking pace.
0 0.5 1 1.5 2+ Mortality 91% Improvement Relative Risk Severe case 70% c19early.org/ex Yuan et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Yuan] Retrospective 164 COVID-19 patients in China, showing physical inactivity associated with an increased risk of severe COVID-19.
0 0.5 1 1.5 2+ Mortality 26% Improvement Relative Risk Case 18% c19early.org/ex Zhang et al. Exercise for COVID-19 Prophylaxis Favors exercise Favors inactivity
[Zhang (B)] UK Biobank retrospective showing significantly lower COVID-19 cases with objectively measured physical activity.
We performed ongoing searches of PubMed, medRxiv, ClinicalTrials.gov, The Cochrane Library, Google Scholar, Collabovid, Research Square, ScienceDirect, Oxford University Press, the reference lists of other studies and meta-analyses, and submissions to the site c19early.org. Search terms were (exercise OR "physical activity") AND COVID-19. Automated searches are performed every few hours with notification of new matches. All studies regarding the use of exercise for COVID-19 that report a comparison with a control group are included in the main analysis. Sensitivity analysis is performed, excluding studies with major issues, epidemiological studies, and studies with minimal available information. This is a living analysis and is updated regularly.
We extracted effect sizes and associated data from all studies. If studies report multiple kinds of effects then the most serious outcome is used in pooled analysis, while other outcomes are included in the outcome specific analyses. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. When results provide an odds ratio, we computed the relative risk when possible, or converted to a relative risk according to [Zhang]. Reported confidence intervals and p-values were used when available, using adjusted values when provided. If multiple types of adjustments are reported including propensity score matching (PSM), the PSM results are used. Adjusted primary outcome results have preference over unadjusted results for a more serious outcome when the adjustments significantly alter results. When needed, conversion between reported p-values and confidence intervals followed [Altman, Altman (B)], and Fisher's exact test was used to calculate p-values for event data. If continuity correction for zero values is required, we use the reciprocal of the opposite arm with the sum of the correction factors equal to 1 [Sweeting]. Results are expressed with RR < 1.0 favoring treatment, and using the risk of a negative outcome when applicable (for example, the risk of death rather than the risk of survival). If studies only report relative continuous values such as relative times, the ratio of the time for the treatment group versus the time for the control group is used. Calculations are done in Python (3.10.8) with scipy (1.9.3), pythonmeta (1.26), numpy (1.23.4), statsmodels (0.13.5), and plotly (5.11.0).
Forest plots are computed using PythonMeta [Deng] with the DerSimonian and Laird random effects model (the fixed effect assumption is not plausible in this case) and inverse variance weighting. Mixed-effects meta-regression results are computed with R (4.1.2) using the metafor (3.0-2) and rms (6.2-0) packages, and using the most serious sufficiently powered outcome.
We received no funding, this research is done in our spare time. We have no affiliations with any pharmaceutical companies or political parties.
We have classified studies as early treatment if most patients are not already at a severe stage at the time of treatment (for example based on oxygen status or lung involvement), and treatment started within 5 days of the onset of symptoms. If studies contain a mix of early treatment and late treatment patients, we consider the treatment time of patients contributing most to the events (for example, consider a study where most patients are treated early but late treatment patients are included, and all mortality events were observed with late treatment patients). We note that a shorter time may be preferable. Antivirals are typically only considered effective when used within a shorter timeframe, for example 0-36 or 0-48 hours for oseltamivir, with longer delays not being effective [McLean, Treanor].
A summary of study results is below. Please submit updates and corrections at the bottom of this page.
A summary of study results is below. Please submit updates and corrections at https://c19early.org/exmeta.html.
Effect extraction follows pre-specified rules as detailed above and gives priority to more serious outcomes. For pooled analyses, the first (most serious) outcome is used, which may differ from the effect a paper focuses on. Other outcomes are used in outcome specific analyses.
[af Geijerstam], 7/5/2021, prospective, Sweden, peer-reviewed, 9 authors, study period March 2020 - September 2020. risk of death, 50.0% lower, OR 0.50, p = 0.005, high vs. low fitness, model 7, RR approximated with OR.
risk of ICU admission, 40.0% lower, OR 0.60, p < 0.001, high vs. low fitness, model 7, RR approximated with OR.
risk of hospitalization, 27.0% lower, OR 0.73, p < 0.001, high vs. low fitness, model 7, RR approximated with OR.
[Ahmadi], 8/31/2021, retrospective, United Kingdom, peer-reviewed, 5 authors. risk of death, 30.0% lower, RR 0.70, p = 0.005, adjusted per study, sufficient vs. inactive, model 2, multivariable.
[Almansour], 2/17/2022, retrospective, Saudi Arabia, peer-reviewed, 12 authors, study period April 2020 - June 2020. risk of case, 5.7% lower, RR 0.94, p = 0.85, high activity levels 35 of 71 (49.3%), low activity levels 38 of 71 (53.5%), NNT 24, adjusted per study, odds ratio converted to relative risk, multivariable.
[Antunes], 6/11/2022, retrospective, Brazil, peer-reviewed, survey, 5 authors, study period September 2020 - December 2020. risk of ICU admission, 80.2% lower, RR 0.20, p = 0.06, high activity levels 1 of 14 (7.1%), low activity levels 9 of 25 (36.0%), NNT 3.5.
risk of miscellaneous, 40.5% lower, RR 0.60, p = 0.48, high activity levels 3 of 14 (21.4%), low activity levels 9 of 25 (36.0%), NNT 6.9, CT abnormalities >50%.
risk of miscellaneous, 72.5% lower, RR 0.27, p = 0.04, high activity levels 2 of 14 (14.3%), low activity levels 13 of 25 (52.0%), NNT 2.7, CT abnormalities 25-50%.
hospitalization time, 43.4% lower, relative time 0.57, p = 0.03, high activity levels 14, low activity levels 25.
miscellaneous, 25.5% lower, relative time 0.74, p = 0.02, high activity levels 14, low activity levels 25.
[Baynouna AlKetbi], 8/23/2021, retrospective, United Arab Emirates, peer-reviewed, 16 authors. risk of death, 98.5% lower, OR 0.01, p = 0.049, adjusted per study, multivariable, RR approximated with OR.
[Beydoun], 3/12/2022, retrospective, USA, peer-reviewed, survey, 7 authors. risk of case, 43.0% lower, OR 0.57, p = 0.05, high activity levels 1,710, low activity levels 448, adjusted per study, multivariable, >1/week vs. none, model 2, RR approximated with OR.
risk of case, 62.0% lower, OR 0.38, p = 0.010, high activity levels 672, low activity levels 448, adjusted per study, multivariable, 1-4/mon vs. none, model 2, RR approximated with OR.
[Bielik], 7/4/2021, retrospective, Slovakia, peer-reviewed, survey, 3 authors, study period 7 December, 2020 - 12 December, 2020. risk of moderate case, 30.4% lower, RR 0.70, p = 0.10, high activity levels 775, low activity levels 365, adjusted per study, physically active group.
risk of case, 9.1% higher, RR 1.09, p = 0.36, high activity levels 775, low activity levels 365, adjusted per study, physically active group.
[Brandenburg], 7/1/2021, retrospective, multiple countries, peer-reviewed, survey, 4 authors. risk of hospitalization, 6.0% higher, OR 1.06, p = 0.60, high activity levels 102, low activity levels 39, adjusted per study, multivariable, PA, >1h vigorous vs. no/low, RR approximated with OR.
risk of hospitalization, 78.0% lower, OR 0.22, p = 0.05, high activity levels 177, low activity levels 34, adjusted per study, multivariable, CRF, 6.2-8.7 vs. >10, RR approximated with OR.
risk of hospitalization, 64.0% lower, OR 0.36, p = 0.04, high activity levels 97, low activity levels 34, adjusted per study, multivariable, CRF, 8.7-10 vs. >10, RR approximated with OR.
risk of severe case, 35.0% lower, OR 0.65, p = 0.30, high activity levels 102, low activity levels 39, adjusted per study, multivariable, PA, >1h vigorous vs. no/low, RR approximated with OR.
risk of severe case, 24.0% lower, OR 0.76, p = 0.60, high activity levels 52, low activity levels 34, adjusted per study, multivariable, CRF, 4.4-6.2 vs. >10, RR approximated with OR.
[Brawner], 10/10/2020, retrospective, USA, peer-reviewed, 10 authors, study period 29 February, 2020 - 30 May, 2020, excluded in exclusion analyses: unadjusted results with no group details. risk of hospitalization, 74.2% lower, OR 0.26, p = 0.001, unadjusted, inverted to make OR<1 favor high activity levels, highest fitness quartile vs. lowest fitness quartile, RR approximated with OR.
[Cho], 4/6/2021, retrospective, South Korea, peer-reviewed, 9 authors. risk of death, 53.0% lower, OR 0.47, p = 0.01, high activity levels 17 of 48 (35.4%) cases, 3,223 of 4,536 (71.1%) controls, case control OR, moderate to vigorous vs. inactive.
risk of case, 10.0% lower, OR 0.90, p < 0.001, high activity levels 3,223 of 4,536 (71.1%) cases, 68,609 of 92,587 (74.1%) controls, NNT 142, case control OR, moderate to vigorous vs. inactive.
[Christensen], 5/5/2021, prospective, United Kingdom, peer-reviewed, 5 authors, study period 16 March, 2020 - 26 July, 2020. risk of death, 63.0% lower, RR 0.37, p = 0.02, high activity levels 543, low activity levels 529, adjusted per study, high fitness vs. low fitness, multivariable.
risk of case, 23.0% lower, RR 0.77, p = 0.20, high activity levels 55 of 543 (10.1%), low activity levels 77 of 529 (14.6%), NNT 23, adjusted per study, high fitness vs. low fitness, multivariable.
[de Souza], 9/30/2021, retrospective, Brazil, peer-reviewed, 8 authors, study period June 2020 - August 2020, trial NCT04396353 (history). risk of mechanical ventilation, 73.2% lower, RR 0.27, p = 0.07, high activity levels 3 of 611 (0.5%), low activity levels 6 of 327 (1.8%), NNT 74, unadjusted, excluded in exclusion analyses: unadjusted results with no group details.
risk of hospitalization, 34.3% lower, RR 0.66, p = 0.046, high activity levels 49 of 611 (8.0%), low activity levels 42 of 327 (12.8%), NNT 21, adjusted per study, sufficient vs. insufficient, model 3, multivariable.
[Ekblom-Bak], 10/19/2021, retrospective, Sweden, peer-reviewed, 13 authors. risk of severe case, 47.6% lower, OR 0.52, p = 0.02, inverted to make OR<1 favor high activity levels, case control OR, model 3, high vs. very low CRF.
[Gao], 11/5/2020, retrospective, China, peer-reviewed, survey, median age 55.0, 11 authors, study period 10 February, 2020 - 1 March, 2020. risk of case, 105.0% higher, HR 2.05, p < 0.001, high activity levels 59 of 105 (56.2%) cases, 69 of 210 (32.9%) controls, case control OR, Cox proportional hazards.
[Gilley], 2/10/2022, retrospective, USA, peer-reviewed, survey, 21 authors, study period September 2020 - December 2020, trial NCT04766788 (history). risk of case, 41.8% higher, RR 1.42, p = 0.55, high activity levels 172 of 1,917 (9.0%), low activity levels 5 of 79 (6.3%), unadjusted.
[Green], 11/7/2022, retrospective, Israel, peer-reviewed, 9 authors, study period 1 February, 2020 - 31 December, 2020. risk of case, 41.7% lower, RR 0.58, p < 0.001, high activity levels 1,267 of 11,144 (11.4%), low activity levels 16,198 of 101,931 (15.9%), adjusted per study, odds ratio converted to relative risk, >3 times per week vs. none, multivariable.