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Aspirin for COVID-19: real-time meta analysis of 50 studies
Covid Analysis, August 8, 2022, DRAFT
https://c19aspirin.com/meta.html
0 0.5 1 1.5+ All studies 14% 50 132,274 Improvement, Studies, Patients Relative Risk Mortality 13% 44 118,565 Ventilation 4% 10 40,612 ICU admission -2% 9 9,589 Hospitalization -1% 7 5,363 Progression 14% 5 2,067 Recovery 9% 3 16,018 Cases 13% 6 10,749 Viral clearance 9% 2 710 RCTs 7% 4 16,917 RCT mortality 6% 3 16,637 Peer-reviewed 14% 45 106,498 Prophylaxis 9% 26 101,469 Early 67% 1 280 Late 21% 23 30,525 Aspirin for COVID-19 c19aspirin.com Aug 2022 Favorsaspirin Favorscontrol after exclusions
Statistically significant improvement is seen for mortality. 22 studies from 20 independent teams in 8 different countries show statistically significant improvements in isolation (17 for the most serious outcome).
Meta analysis using the most serious outcome reported shows 14% [8‑19%] improvement. Results are worse for Randomized Controlled Trials, similar after exclusions, and similar for peer-reviewed studies. Early treatment is more effective than late treatment.
0 0.5 1 1.5+ All studies 14% 50 132,274 Improvement, Studies, Patients Relative Risk Mortality 13% 44 118,565 Ventilation 4% 10 40,612 ICU admission -2% 9 9,589 Hospitalization -1% 7 5,363 Progression 14% 5 2,067 Recovery 9% 3 16,018 Cases 13% 6 10,749 Viral clearance 9% 2 710 RCTs 7% 4 16,917 RCT mortality 6% 3 16,637 Peer-reviewed 14% 45 106,498 Prophylaxis 9% 26 101,469 Early 67% 1 280 Late 21% 23 30,525 Aspirin for COVID-19 c19aspirin.com Aug 2022 Favorsaspirin Favorscontrol after exclusions
Studies to date do not show a significant benefit for mechanical ventilation and ICU admission. Benefit may be more likely without coadministered anticoagulants. The RECOVERY RCT shows 4% [-4‑11%] lower mortality for all patients, however when restricting to non-LMWH patients there was 17% [-4‑34%] improvement, consistent with the mortality results of all studies, 13% [7‑20%], and the 16% improvement in the REMAP-CAP RCT.
While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 4% of aspirin studies show zero events in the treatment arm. Multiple treatments are typically used in combination, and other treatments are significantly more effective.
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. [Banaser] present another meta analysis for aspirin, showing significant improvements for mortality and mechanical ventilation.
Highlights
Aspirin reduces risk for COVID-19 with very high confidence for mortality and in pooled analysis, low confidence for recovery and viral clearance, and very low confidence for cases. Benefit may be more likely without coadministered anticoagulants.
We show traditional outcome specific analyses and combined evidence from all studies, incorporating treatment delay, a primary confounding factor in COVID-19 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+ Connors (DB RCT) 67% 0.33 [0.01-7.96] hosp. 0/144 1/136 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.5 Early treatment 67% 0.33 [0.01-7.96] 0/144 1/136 67% improvement Alamdari -28% 1.28 [0.67-2.43] death 9/53 54/406 Improvement, RR [CI] Treatment Control Husain 80% 0.20 [0.01-3.55] death 0/11 3/31 Goshua (PSM) 35% 0.65 [0.42-0.98] death 319 (n) 319 (n) Meizlish (PSM) 48% 0.52 [0.34-0.81] death 319 (n) 319 (n) Liu (PSM) 75% 0.25 [0.07-0.87] death 2/28 11/204 Mura (PSM) 15% 0.85 [0.69-1.01] death 527 (n) 527 (n) Chow 47% 0.53 [0.31-0.90] death 26/98 73/314 Haji Aghajani 25% 0.75 [0.57-0.99] death 336 (n) 655 (n) Elhadi (ICU) 10% 0.90 [0.67-1.21] death 22/40 259/425 ICU patients Sahai (PSM) 13% 0.87 [0.56-1.34] death 33/248 38/248 Pourhoseingholi -32% 1.32 [1.02-1.71] death 71/290 268/2,178 Vahedian-Azimi 22% 0.78 [0.33-1.74] death 13/337 28/250 Abdelwahab -8% 1.08 [0.15-3.82] ventilation 11/31 6/36 Karruli (ICU) 46% 0.54 [0.09-3.13] death 1/5 22/27 ICU patients Al Harthi (PSM) 27% 0.73 [0.56-0.97] death 98/176 107/173 Kim (PSM) 34% 0.66 [0.36-1.23] death 14/124 23/135 Zhao 43% 0.57 [0.41-0.78] death 121/473 140/473 RECOVERY (RCT) 4% 0.96 [0.89-1.04] death 7,351 (n) 7,541 (n) Mustafa 44% 0.56 [0.21-1.51] death 4/66 41/378 Bradbury (RCT) 16% 0.84 [0.70-1.00] death 165/563 170/521 Chow (PSW) 13% 0.87 [0.81-0.93] death Santoro (PSM) 38% 0.62 [0.42-0.92] death 360 (n) 2,949 (n) Ghati (RCT) 22% 0.78 [0.31-1.98] death 11/442 7/219 Tau​2 = 0.02, I​2 = 64.4%, p < 0.0001 Late treatment 21% 0.79 [0.72-0.87] 601/12,197 1,250/18,328 21% improvement Huh 71% 0.29 [0.14-0.58] cases population-based cohort Improvement, RR [CI] Treatment Control Wang 58% 0.42 [0.01-1.98] death 1/9 13/49 Formiga (PSM) -3% 1.03 [0.94-1.13] death 1,000/3,291 874/2,885 Yuan 4% 0.96 [0.47-1.72] death 11/52 29/131 Osborne (PSM) 59% 0.41 [0.35-0.48] death 272/6,300 661/6,300 Merzon 28% 0.72 [0.53-0.99] cases 73/1,621 589/8,856 Mulhem -14% 1.14 [0.93-1.40] death 300/1,354 216/1,865 Pan -13% 1.13 [0.70-1.82] death 239 (n) 523 (n) Oh 1% 0.99 [0.65-1.50] death n/a n/a Son (PSM) 24% 0.76 [0.34-1.71] death case control Ma (PSM) 9% 0.91 [0.82-1.02] death Chow (PSM) 19% 0.81 [0.76-0.87] death 1,280/6,781 2,271/10,566 Kim (PSM) -700% 8.00 [1.07-59.6] death 6/15 1/20 Basheer -13% 1.13 [1.05-1.21] death 45/140 29/250 Sisinni -7% 1.07 [0.89-1.29] death 93/253 251/731 Pérez-Segura -49% 1.49 [1.20-1.80] death 66/155 183/608 Sullerot (PSW) -10% 1.10 [0.81-1.49] death 101/301 224/746 Monserrat V.. (PSM) -31% 1.31 [1.01-1.71] death n/a n/a Levy 26% 0.74 [0.49-1.10] death/hosp. 29/159 178/690 Nimer 4% 0.96 [0.69-1.33] hosp. 83/427 136/1,721 Gogtay -6% 1.06 [0.51-1.89] death 12/38 21/87 Campbell (PSW) 3% 0.97 [0.95-1.00] death 419 (n) 20,311 (n) Lal 11% 0.89 [0.82-0.97] death 4,691 (n) 16,888 (n) Botton -4% 1.04 [0.98-1.10] death/int. Malik 14% 0.86 [0.39-1.80] death 15/87 24/223 Abul 33% 0.67 [0.47-0.95] death 46/511 201/1,176 Tau​2 = 0.03, I​2 = 90.3%, p = 0.053 Prophylaxis 9% 0.91 [0.83-1.00] 3,433/26,843 5,901/74,626 9% improvement All studies 14% 0.86 [0.81-0.92] 4,034/39,184 7,152/93,090 14% improvement 50 aspirin COVID-19 studies c19aspirin.com Aug 2022 Tau​2 = 0.03, I​2 = 85.6%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) Favors aspirin Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Connors (DB RCT) 67% hospitalization Improvement Relative Risk [CI] Tau​2 = 0.00, I​2 = 0.0%, p = 0.5 Early treatment 67% 67% improvement Alamdari -28% death Husain 80% death Goshua (PSM) 35% death Meizlish (PSM) 48% death Liu (PSM) 75% death Mura (PSM) 15% death Chow 47% death Haji Aghajani 25% death Elhadi (ICU) 10% death ICU patients Sahai (PSM) 13% death Pourhoseingholi -32% death Vahedian-Azimi 22% death Abdelwahab -8% ventilation Karruli (ICU) 46% death ICU patients Al Harthi (PSM) 27% death Kim (PSM) 34% death Zhao 43% death RECOVERY (RCT) 4% death Mustafa 44% death Bradbury (RCT) 16% death Chow (PSW) 13% death Santoro (PSM) 38% death Ghati (RCT) 22% death Tau​2 = 0.02, I​2 = 64.4%, p < 0.0001 Late treatment 21% 21% improvement Huh 71% case Wang 58% death Formiga (PSM) -3% death Yuan 4% death Osborne (PSM) 59% death Merzon 28% case Mulhem -14% death Pan -13% death Oh 1% death Son (PSM) 24% death Ma (PSM) 9% death Chow (PSM) 19% death Kim (PSM) -700% death Basheer -13% death Sisinni -7% death Pérez-Segura -49% death Sullerot (PSW) -10% death Monserrat V.. (PSM) -31% death Levy 26% death/hosp. Nimer 4% hospitalization Gogtay -6% death Campbell (PSW) 3% death Lal 11% death Botton -4% death/intubation Malik 14% death Abul 33% death Tau​2 = 0.03, I​2 = 90.3%, p = 0.053 Prophylaxis 9% 9% improvement All studies 14% 14% improvement 50 aspirin COVID-19 studies c19aspirin.com Aug 2022 Tau​2 = 0.03, I​2 = 85.6%, p < 0.0001 Effect extraction pre-specifiedRotate device for details Favors aspirin Favors control
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 concerning the use of aspirin for COVID-19. 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.
Figure 2 shows stages of possible treatment for COVID-19. Prophylaxis refers to regularly taking medication before becoming sick, in order to prevent or minimize infection. Early Treatment refers to treatment immediately or soon after symptoms appear, while Late Treatment refers to more delayed treatment.
Figure 2. Treatment stages.
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, 12, and 13 show forest plots for a random effects meta-analysis of all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, progression, recovery, cases, viral clearance, and peer reviewed studies.
0 0.5 1 1.5+ ALL STUDIES MORTALITY VENTILATION ICU ADMISSION HOSPITALIZATION PROGRESSION RECOVERY CASES VIRAL CLEARANCE RANDOMIZED CONTROLLED TRIALS RCT MORTALITY PEER-REVIEWED After Exclusions ALL STUDIES All Prophylaxis Early Late Aspirin for COVID-19 C19ASPIRIN.COM 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
Early treatment 1 1 100% 67% improvement
RR 0.33 [0.01‑7.96]
p = 0.5
Late treatment 20 23 87.0% 21% improvement
RR 0.79 [0.72‑0.87]
p < 0.0001
Prophylaxis 15 26 57.7% 9% improvement
RR 0.91 [0.83‑1.00]
p = 0.053
All studies 36 50 72.0% 14% improvement
RR 0.86 [0.81‑0.92]
p < 0.0001
Table 1. Results by treatment stage.
Studies Early treatment Late treatment Prophylaxis PatientsAuthors
All studies 5067% [-696‑99%]21% [13‑28%]9% [-0‑17%] 132,274 739
With exclusions 4667% [-696‑99%]22% [13‑30%]10% [1‑18%] 127,687 694
Peer-reviewed 4567% [-696‑99%]23% [15‑30%]6% [-4‑14%] 106,498 696
Randomized Controlled TrialsRCTs 467% [-696‑99%]6% [-1‑13%] 16,917 115
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+ Connors (DB RCT) 67% 0.33 [0.01-7.96] hosp. 0/144 1/136 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.5 Early treatment 67% 0.33 [0.01-7.96] 0/144 1/136 67% improvement Alamdari -28% 1.28 [0.67-2.43] death 9/53 54/406 Improvement, RR [CI] Treatment Control Husain 80% 0.20 [0.01-3.55] death 0/11 3/31 Goshua (PSM) 35% 0.65 [0.42-0.98] death 319 (n) 319 (n) Meizlish (PSM) 48% 0.52 [0.34-0.81] death 319 (n) 319 (n) Liu (PSM) 75% 0.25 [0.07-0.87] death 2/28 11/204 Mura (PSM) 15% 0.85 [0.69-1.01] death 527 (n) 527 (n) Chow 47% 0.53 [0.31-0.90] death 26/98 73/314 Haji Aghajani 25% 0.75 [0.57-0.99] death 336 (n) 655 (n) Elhadi (ICU) 10% 0.90 [0.67-1.21] death 22/40 259/425 ICU patients Sahai (PSM) 13% 0.87 [0.56-1.34] death 33/248 38/248 Pourhoseingholi -32% 1.32 [1.02-1.71] death 71/290 268/2,178 Vahedian-Azimi 22% 0.78 [0.33-1.74] death 13/337 28/250 Abdelwahab -8% 1.08 [0.15-3.82] ventilation 11/31 6/36 Karruli (ICU) 46% 0.54 [0.09-3.13] death 1/5 22/27 ICU patients Al Harthi (PSM) 27% 0.73 [0.56-0.97] death 98/176 107/173 Kim (PSM) 34% 0.66 [0.36-1.23] death 14/124 23/135 Zhao 43% 0.57 [0.41-0.78] death 121/473 140/473 RECOVERY (RCT) 4% 0.96 [0.89-1.04] death 7,351 (n) 7,541 (n) Mustafa 44% 0.56 [0.21-1.51] death 4/66 41/378 Bradbury (RCT) 16% 0.84 [0.70-1.00] death 165/563 170/521 Chow (PSW) 13% 0.87 [0.81-0.93] death Santoro (PSM) 38% 0.62 [0.42-0.92] death 360 (n) 2,949 (n) Ghati (RCT) 22% 0.78 [0.31-1.98] death 11/442 7/219 Tau​2 = 0.02, I​2 = 64.4%, p < 0.0001 Late treatment 21% 0.79 [0.72-0.87] 601/12,197 1,250/18,328 21% improvement Huh 71% 0.29 [0.14-0.58] cases population-based cohort Improvement, RR [CI] Treatment Control Wang 58% 0.42 [0.01-1.98] death 1/9 13/49 Formiga (PSM) -3% 1.03 [0.94-1.13] death 1,000/3,291 874/2,885 Yuan 4% 0.96 [0.47-1.72] death 11/52 29/131 Osborne (PSM) 59% 0.41 [0.35-0.48] death 272/6,300 661/6,300 Merzon 28% 0.72 [0.53-0.99] cases 73/1,621 589/8,856 Mulhem -14% 1.14 [0.93-1.40] death 300/1,354 216/1,865 Pan -13% 1.13 [0.70-1.82] death 239 (n) 523 (n) Oh 1% 0.99 [0.65-1.50] death n/a n/a Son (PSM) 24% 0.76 [0.34-1.71] death case control Ma (PSM) 9% 0.91 [0.82-1.02] death Chow (PSM) 19% 0.81 [0.76-0.87] death 1,280/6,781 2,271/10,566 Kim (PSM) -700% 8.00 [1.07-59.6] death 6/15 1/20 Basheer -13% 1.13 [1.05-1.21] death 45/140 29/250 Sisinni -7% 1.07 [0.89-1.29] death 93/253 251/731 Pérez-Segura -49% 1.49 [1.20-1.80] death 66/155 183/608 Sullerot (PSW) -10% 1.10 [0.81-1.49] death 101/301 224/746 Monserrat V.. (PSM) -31% 1.31 [1.01-1.71] death n/a n/a Levy 26% 0.74 [0.49-1.10] death/hosp. 29/159 178/690 Nimer 4% 0.96 [0.69-1.33] hosp. 83/427 136/1,721 Gogtay -6% 1.06 [0.51-1.89] death 12/38 21/87 Campbell (PSW) 3% 0.97 [0.95-1.00] death 419 (n) 20,311 (n) Lal 11% 0.89 [0.82-0.97] death 4,691 (n) 16,888 (n) Botton -4% 1.04 [0.98-1.10] death/int. Malik 14% 0.86 [0.39-1.80] death 15/87 24/223 Abul 33% 0.67 [0.47-0.95] death 46/511 201/1,176 Tau​2 = 0.03, I​2 = 90.3%, p = 0.053 Prophylaxis 9% 0.91 [0.83-1.00] 3,433/26,843 5,901/74,626 9% improvement All studies 14% 0.86 [0.81-0.92] 4,034/39,184 7,152/93,090 14% improvement 50 aspirin COVID-19 studies c19aspirin.com Aug 2022 Tau​2 = 0.03, I​2 = 85.6%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) Favors aspirin Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Connors (DB RCT) 67% hospitalization Improvement Relative Risk [CI] Tau​2 = 0.00, I​2 = 0.0%, p = 0.5 Early treatment 67% 67% improvement Alamdari -28% death Husain 80% death Goshua (PSM) 35% death Meizlish (PSM) 48% death Liu (PSM) 75% death Mura (PSM) 15% death Chow 47% death Haji Aghajani 25% death Elhadi (ICU) 10% death ICU patients Sahai (PSM) 13% death Pourhoseingholi -32% death Vahedian-Azimi 22% death Abdelwahab -8% ventilation Karruli (ICU) 46% death ICU patients Al Harthi (PSM) 27% death Kim (PSM) 34% death Zhao 43% death RECOVERY (RCT) 4% death Mustafa 44% death Bradbury (RCT) 16% death Chow (PSW) 13% death Santoro (PSM) 38% death Ghati (RCT) 22% death Tau​2 = 0.02, I​2 = 64.4%, p < 0.0001 Late treatment 21% 21% improvement Huh 71% case Wang 58% death Formiga (PSM) -3% death Yuan 4% death Osborne (PSM) 59% death Merzon 28% case Mulhem -14% death Pan -13% death Oh 1% death Son (PSM) 24% death Ma (PSM) 9% death Chow (PSM) 19% death Kim (PSM) -700% death Basheer -13% death Sisinni -7% death Pérez-Segura -49% death Sullerot (PSW) -10% death Monserrat V.. (PSM) -31% death Levy 26% death/hosp. Nimer 4% hospitalization Gogtay -6% death Campbell (PSW) 3% death Lal 11% death Botton -4% death/intubation Malik 14% death Abul 33% death Tau​2 = 0.03, I​2 = 90.3%, p = 0.053 Prophylaxis 9% 9% improvement All studies 14% 14% improvement 50 aspirin COVID-19 studies c19aspirin.com Aug 2022 Tau​2 = 0.03, I​2 = 85.6%, p < 0.0001 Effect extraction pre-specifiedRotate device for details Favors aspirin Favors control
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+ Alamdari -28% 1.28 [0.67-2.43] 9/53 54/406 Improvement, RR [CI] Treatment Control Husain 80% 0.20 [0.01-3.55] 0/11 3/31 Goshua (PSM) 35% 0.65 [0.42-0.98] 319 (n) 319 (n) Meizlish (PSM) 48% 0.52 [0.34-0.81] 319 (n) 319 (n) Liu (PSM) 75% 0.25 [0.07-0.87] 2/28 11/204 Mura (PSM) 15% 0.85 [0.69-1.01] 527 (n) 527 (n) Chow 47% 0.53 [0.31-0.90] 26/98 73/314 Haji Aghajani 25% 0.75 [0.57-0.99] 336 (n) 655 (n) Elhadi (ICU) 10% 0.90 [0.67-1.21] 22/40 259/425 ICU patients Sahai (PSM) 13% 0.87 [0.56-1.34] 33/248 38/248 Pourhoseingholi -32% 1.32 [1.02-1.71] 71/290 268/2,178 Vahedian-Azimi 22% 0.78 [0.33-1.74] 13/337 28/250 Karruli (ICU) 46% 0.54 [0.09-3.13] 1/5 22/27 ICU patients Al Harthi (PSM) 27% 0.73 [0.56-0.97] 98/176 107/173 Kim (PSM) 34% 0.66 [0.36-1.23] 14/124 23/135 Zhao 43% 0.57 [0.41-0.78] 121/473 140/473 RECOVERY (RCT) 4% 0.96 [0.89-1.04] 7,351 (n) 7,541 (n) Mustafa 44% 0.56 [0.21-1.51] 4/66 41/378 Bradbury (RCT) 16% 0.84 [0.70-1.00] 165/563 170/521 Chow (PSW) 13% 0.87 [0.81-0.93] Santoro (PSM) 38% 0.62 [0.42-0.92] 360 (n) 2,949 (n) Ghati (RCT) 22% 0.78 [0.31-1.98] 11/442 7/219 Tau​2 = 0.02, I​2 = 65.9%, p < 0.0001 Late treatment 21% 0.79 [0.72-0.87] 590/12,166 1,244/18,292 21% improvement Wang 58% 0.42 [0.01-1.98] 1/9 13/49 Improvement, RR [CI] Treatment Control Formiga (PSM) -3% 1.03 [0.94-1.13] 1,000/3,291 874/2,885 Yuan