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Exercise for COVID-19: real-time meta analysis of 36 studies
Covid Analysis, August 14, 2022, DRAFT
https://c19early.com/exmeta.html
0 0.5 1 1.5+ All studies 40% 36 1,464,894 Improvement, Studies, Patients Relative Risk Mortality 44% 13 1,437,929 Ventilation 46% 2 43,773 ICU admission 41% 4 708,149 Hospitalization 38% 9 666,393 Recovery 57% 2 66 Cases 20% 14 77,841 Peer-reviewed 40% 35 1,464,894 Prophylaxis 40% 36 1,464,894 Exercise for COVID-19 c19early.com/ex Aug 2022 Favorsexercise Favorsinactivity after exclusions
Statistically significant improvements are seen for mortality, ventilation, ICU admission, hospitalization, progression, recovery, and cases. 28 studies from 28 independent teams in 14 different countries show statistically significant improvements in isolation (21 for the most serious outcome).
Meta analysis using the most serious outcome reported shows 40% [33‑47%] improvement. Results are similar after exclusions and similar for peer-reviewed studies.
Results are robust — in exclusion sensitivity analysis 31 of 36 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 40% 36 1,464,894 Improvement, Studies, Patients Relative Risk Mortality 44% 13 1,437,929 Ventilation 46% 2 43,773 ICU admission 41% 4 708,149 Hospitalization 38% 9 666,393 Recovery 57% 2 66 Cases 20% 14 77,841 Peer-reviewed 40% 35 1,464,894 Prophylaxis 40% 36 1,464,894 Exercise for COVID-19 c19early.com/ex Aug 2022 Favorsexercise Favorsinactivity after exclusions
Studies analyze exercise/physical activity levels before infection, comparing regular/moderate exercise vs. lower/no exercise. Note that risk may increase with more extreme activity levels.
No treatment, vaccine, or intervention is 100% available and effective for all variants. All practical, effective, and safe means should be used. Denying the efficacy of treatments increases mortality, morbidity, collateral damage, and endemic risk.
All data to reproduce this paper and sources are in the appendix. Other meta analyses for exercise can be found in [Li, Rahmati], showing significant improvements for mortality, ICU admission, and hospitalization.
Highlights
Exercise reduces risk for COVID-19 with very high confidence for mortality, ventilation, ICU admission, hospitalization, recovery, cases, and in pooled analysis, and high confidence for progression.
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 43 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 Zhang 26% 0.74 [0.48-1.14] death n/a n/a 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 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 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 Tau​2 = 0.06, I​2 = 67.5%, p < 0.0001 Prophylaxis 40% 0.60 [0.53-0.67] 1,826/885,655 1,432/579,239 40% improvement All studies 40% 0.60 [0.53-0.67] 1,826/885,655 1,432/579,239 40% improvement 36 exercise COVID-19 studies c19early.com/ex Aug 2022 Tau​2 = 0.06, I​2 = 67.5%, 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 Improvement Relative Risk [CI] Brawner 74% hospitalization Zhang 26% death 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 Steenkamp 42% death Gilley -42% case Beydoun 43% case Salgado-Aranda 83% death Paul 38% recovery Kontopoulou 66% recovery Malisoux 63% progression Antunes 80% ICU admission Tau​2 = 0.06, I​2 = 67.5%, p < 0.0001 Prophylaxis 40% 40% improvement All studies 40% 40% improvement 36 exercise COVID-19 studies c19early.com/ex Aug 2022 Tau​2 = 0.06, I​2 = 67.5%, p < 0.0001 Effect extraction pre-specifiedRotate device for details Favors exercise Favors inactivity
Figure 1. A. Random effects meta-analysis. This plot shows pooled effects, discussion can be found in the heterogeneity section, and results for specific outcomes can be found in the individual outcome analyses. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix. B. Scatter plot showing the distribution of effects reported in studies. C. History of all reported effects (chronological within treatment stages).
Introduction
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.
Physical Inactivity
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. 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 increases with more extreme activity levels [Nieman].
Figure 2. Risk may increase with more extreme activity levels, as seen with upper respiratory tract infections [Nieman].
Results
Figure 3 shows a visual overview of the results, with details in Table 1 and Table 2. Figure 4, 5, 6, 7, 8, 9, 10, 11, and 12 show forest plots for a random effects meta-analysis of all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, progression, recovery, cases, and peer reviewed studies.
0 0.5 1 1.5+ ALL STUDIES MORTALITY VENTILATION ICU ADMISSION HOSPITALIZATION RECOVERY CASES PEER-REVIEWED After Exclusions ALL STUDIES All Prophylaxis Exercise for COVID-19 C19EARLY.COM/EX AUG 2022
Figure 3. Overview of results.
Treatment timeNumber of studies reporting positive effects Total number of studiesPercentage of studies reporting positive effects Random effects meta-analysis results
Prophylaxis 34 36 94.4% 40% improvement
RR 0.60 [0.53‑0.67]
p < 0.0001
All studies 34 36 94.4% 40% improvement
RR 0.60 [0.53‑0.67]
p < 0.0001
Table 1. Results by treatment stage.
Studies Prophylaxis PatientsAuthors
All studies 3640% [33‑47%] 1,464,894 354
With exclusions 3338% [31‑45%] 1,463,862 330
Peer-reviewed 3540% [33‑47%] 1,464,894 352
Table 2. Results by treatment stage for all studies and with different exclusions.
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 Zhang 26% 0.74 [0.48-1.14] death n/a n/a 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 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 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 Tau​2 = 0.06, I​2 = 67.5%, p < 0.0001 Prophylaxis 40% 0.60 [0.53-0.67] 1,826/885,655 1,432/579,239 40% improvement All studies 40% 0.60 [0.53-0.67] 1,826/885,655 1,432/579,239 40% improvement 36 exercise COVID-19 studies c19early.com/ex Aug 2022 Tau​2 = 0.06, I​2 = 67.5%, 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 Improvement Relative Risk [CI] Brawner 74% hospitalization Zhang 26% death 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 Steenkamp 42% death Gilley -42% case Beydoun 43% case Salgado-Aranda 83% death Paul 38% recovery Kontopoulou 66% recovery Malisoux 63% progression Antunes 80% ICU admission Tau​2 = 0.06, I​2 = 67.5%, p < 0.0001 Prophylaxis 40% 40% improvement All studies 40% 40% improvement 36 exercise COVID-19 studies c19early.com/ex Aug 2022 Tau​2 = 0.06, I​2 = 67.5%, p < 0.0001 Effect extraction pre-specifiedRotate device for details Favors exercise Favors inactivity
Figure 4. Random effects meta-analysis for all studies with pooled effects. This plot shows pooled effects, discussion can be found in the heterogeneity section, and results for specific outcomes can be found in the individual outcome analyses. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Zhang 26% 0.74 [0.48-1.14] n/a n/a Improvement, RR [CI] Treatment Control Yates 45% 0.55 [0.38-0.79] 72/163,912 62/30,119 Cho 53% 0.47 [0.26-0.87] case control Sallis 59% 0.41 [0.22-0.76] 11/3,118 170/6,984 Christensen 63% 0.37 [0.16-0.85] 543 (n) 529 (n) Yuan 91% 0.09 [0.01-1.65] 0/61 6/103 af Geijerstam 50% 0.50 [0.31-0.81] 318,902 (n) 336,271 (n) Lee 74% 0.26 [0.07-0.99] 2/11,072 32/41,293 Baynouna AlKetbi 98% 0.01 [0.00-0.44] n/a n/a Ahmadi 30% 0.70 [0.54-0.89] 160/232,613 112/95,221 Hamrouni 29% 0.71 [0.55-0.92] 138/106,006 109/47,827 Steenkamp 42% 0.58 [0.50-0.68] 29,469 (n) 13,366 (n) Salgado-Aranda 83% 0.17 [0.05-0.56] 4/223 41/297 Tau​2 = 0.03, I​2 = 41.7%, p < 0.0001 Prophylaxis 44% 0.56 [0.48-0.66] 387/865,919 532/572,010 44% improvement All studies 44% 0.56 [0.48-0.66] 387/865,919 532/572,010 44% improvement 13 exercise COVID-19 mortality results c19early.com/ex Aug 2022 Tau​2 = 0.03, I​2 = 41.7%, p < 0.0001 Favors exercise Favors inactivity
Figure 5. Random effects meta-analysis for mortality results.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ de Souza 73% 0.27 [0.07-1.06] 3/611 6/327 Improvement, RR [CI] Treatment Control Steenkamp 45% 0.55 [0.47-0.64] 29,469 (n) 13,366 (n) Tau​2 = 0.01, I​2 = 3.4%, p < 0.0001 Prophylaxis 46% 0.54 [0.43-0.68] 3/30,080 6/13,693 46% improvement All studies 46% 0.54 [0.43-0.68] 3/30,080 6/13,693 46% improvement 2 exercise COVID-19 mechanical ventilation results c19early.com/ex Aug 2022 Tau​2 = 0.01, I​2 = 3.4%, p < 0.0001 Favors exercise Favors inactivity
Figure 6. Random effects meta-analysis for ventilation.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Sallis 42% 0.58 [0.40-0.85] 32/3,118 195/6,984 Improvement, RR [CI] Treatment Control af Geijerstam 40% 0.60 [0.46-0.80] 318,902 (n) 336,271 (n) Steenkamp 41% 0.59 [0.52-0.66] 29,469 (n) 13,366 (n) Antunes 80% 0.20 [0.03-1.41] 1/14 9/25 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Prophylaxis 41% 0.59 [0.53-0.65] 33/351,503 204/356,646 41% improvement All studies 41% 0.59 [0.53-0.65] 33/351,503 204/356,646 41% improvement 4 exercise COVID-19 ICU results c19early.com/ex Aug 2022 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Favors exercise Favors inactivity
Figure 7. Random effects meta-analysis for ICU admission.
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 Sallis 53% 0.47 [0.38-0.58] hosp. 99/3,118 732/6,984 Latorre-Román 76% 0.24 [0.05-1.04] hosp. n/a n/a Brandenburg -6% 1.06 [0.23-4.79] hosp. 102 (n) 39 (n) af Geijerstam 27% 0.73 [0.64-0.83] hosp. 318,902 (n) 336,271 (n) Maltagliati 52% 0.48 [0.25-0.87] hosp. n/a n/a de Souza 34% 0.66 [0.43-0.99] hosp. 49/611 42/327 Antunes 43% 0.57 [0.34-0.95] hosp. time 14 (n) 25 (n) Tau​2 = 0.07, I​2 = 80.0%, p < 0.0001 Prophylaxis 38% 0.62 [0.50-0.78] 148/322,747 774/343,646 38% improvement All studies 38% 0.62 [0.50-0.78] 148/322,747 774/343,646 38% improvement 9 exercise COVID-19 hospitalization results c19early.com/ex Aug 2022 Tau​2 = 0.07, I​2 = 80.0%, p < 0.0001 Favors exercise Favors inactivity
Figure 8. Random effects meta-analysis for hospitalization.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Malisoux 63% 0.37 [0.14-0.98] 115 (n) 108 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.045 Prophylaxis 63% 0.37 [0.14-0.98] 0/115 0/108 63% improvement All studies 63% 0.37 [0.14-0.98] 0/115 0/108 63% improvement 1 exercise COVID-19 progression result c19early.com/ex Aug 2022 Tau​2 = 0.00, I​2 = 0.0%, p = 0.045 Favors exercise Favors inactivity
Figure 9. Random effects meta-analysis for progression.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Paul 38% 0.62 [0.30-1.20] no recov. n/a n/a Improvement, RR [CI] Treatment Control Kontopoulou 66% 0.34 [0.24-0.47] recov. time 42 (n) 24 (n) Tau​2 = 0.11, I​2 = 60.7%, p = 0.0036 Prophylaxis 57% 0.43 [0.24-0.76] 0/42 0/24 57% improvement All studies 57% 0.43 [0.24-0.76] 0/42 0/24 57% improvement 2 exercise COVID-19 recovery results c19early.com/ex Aug 2022 Tau​2 = 0.11, I​2 = 60.7%, p = 0.0036 Favors exercise Favors inactivity
Figure 10. Random effects meta-analysis for recovery.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Zhang 18% 0.82 [0.69-0.96] cases n/a n/a Improvement, RR [CI] Treatment Control Holt 17% 0.83 [0.63-1.09] cases n/a n/a Cho 10% 0.90 [0.86-0.95] cases case control Christensen 23% 0.77 [0.52-1.15] cases 55/543 77/529 Marcus 42% 0.58 [0.48-0.71] symp. case 240/10,627 134/3,708 Bielik -9% 1.09 [0.69-1.73] cases 775 (n) 365 (n) Lee 16% 0.84 [0.73-0.98] cases 291/11,072 1,293/41,293 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 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) Huang 66% 0.34 [0.17-0.70] cases n/a n/a Gilley -42% 1.42 [0.60-3.35] cases 172/1,917 5/79 Beydoun 43% 0.57 [0.32-1.01] cases 1,710 (n) 448 (n) Tau​2 = 0.02, I​2 = 69.4%, p < 0.0001 Prophylaxis 20% 0.80 [0.72-0.89] 1,685/30,071 1,996/47,770 20% improvement All studies 20% 0.80 [0.72-0.89] 1,685/30,071 1,996/47,770 20% improvement 14 exercise COVID-19 case results c19early.com/ex Aug 2022 Tau​2 = 0.02, I​2 = 69.4%, p < 0.0001 Favors exercise Favors inactivity
Figure 11. Random effects meta-analysis for cases.
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 Zhang 26% 0.74 [0.48-1.14] death n/a n/a Tavakol 69% 0.31 [0.10-1.02] severe case