Aspirin for COVID-19: real-time analysis of all 46 studies

Aspirin for COVID-19: real-time meta analysis of 44 studies

Covid Analysis (Preprint) (meta analysis)

• Statistically significant improvement is seen for mortality. 20 studies from 8 different countries show statistically significant improvements in isolation (15 for the most serious outcome).

• Meta analysis using the most serious outcome reported shows 14% [7‑20%] 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.

• Results are robust — in exclusion sensitivity analysis 14 of 44 studies must be excluded to avoid finding statistically significant efficacy in pooled analysis.

• 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% [6‑19%], 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 5% 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.

Covid Analysis et al., 5/22/2022, preprint, 1 author.

Pre-Hospital Aspirin Use and Patient Outcomes in Covid-19: Results from the International Viral Infection and Respiratory Illness Universal Study (Virus)

Lal et al., AJRCCM Conference (Preprint)

Retrospective 21,579 hospitalized COVID-19 patients mostly in the USA, showing lower risk of mortality and severity with existing aspirin use.

risk of death, 11.0% lower, OR 0.89, p = 0.01, treatment 4,691, control 16,888, adjusted, multivariable, RR approximated with OR.

risk of severe case, 9.0% lower, OR 0.91, p = 0.02, treatment 4,691, control 16,888, adjusted, multivariable, RR approximated with OR.

Lal et al., 5/5/2022, retrospective, USA, North America, preprint, 8 authors, study period January 2020 - September 2021.

Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen and relationship with mortality among United States Veterans after testing positive for COVID-19

Campbell et al., PLOS ONE, doi:10.1371/journal.pone.0267462

Retrospective 28,856 COVID-19 patients in the USA, showing no significant difference in mortality for chronic aspirin use vs. sporadic NSAID use. Since aspirin is available OTC and authors only tracked prescriptions, many patients classified as sporadic users may have been chronic users.

risk of death, 3.0% lower, OR 0.97, p = 0.06, treatment 419, control 20,311, adjusted, inverse propensity weighting, multivariable, day 60, RR approximated with OR.

risk of death, 2.0% lower, OR 0.98, p = 0.10, treatment 419, control 20,311, adjusted, inverse propensity weighting, multivariable, day 30, RR approximated with OR.

Campbell et al., 5/5/2022, retrospective, USA, North America, peer-reviewed, 4 authors, study period 2 March, 2020 - 14 December, 2020.

Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19

Chow et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2022.3890

Retrospective 112,269 hospitalized COVID-19 patients in the USA, showing lower mortality with aspirin treatment.

risk of death, 13.5% lower, RR 0.87, p < 0.001, treatment 1,410 of 13,795 (10.2%), control 11,577 of 98,275 (11.8%), NNT 64, adjusted, OR converted to RR, inverse propensity weighting.

Chow et al., 3/24/2022, retrospective, USA, North America, peer-reviewed, median age 63.0, 89 authors.

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

Bradbury et al., JAMA, doi:10.1001/jama.2022.2910

RCT 1,557 critical patients, showing significantly lower mortality with aspirin, with 97.5% posterior probability of efficacy.
REMAP-CAP. NCT02735707.

risk of death, 16.0% lower, HR 0.84, p = 0.05, treatment 165 of 563 (29.3%), control 170 of 521 (32.6%), NNT 30, Kaplan–Meier, day 90.

risk of no hospital discharge, 16.9% lower, RR 0.83, p = 0.08, treatment 161 of 563 (28.6%), control 167 of 521 (32.1%), NNT 29, adjusted, OR converted to RR.

risk of progression, 21.0% lower, RR 0.79, p = 0.02, treatment 204 of 563 (36.2%), control 212 of 521 (40.7%), adjusted, OR converted to RR, combined death/thrombosis.

risk of progression, 4.8% lower, OR 0.95, p = 0.67, treatment 563, control 521, adjusted, support-free days, primary outcome, RR approximated with OR.

Bradbury et al., 3/22/2022, Randomized Controlled Trial, multiple countries, multiple regions, peer-reviewed, 73 authors, study period 30 October, 2020 - 23 June, 2021, trial NCT02735707.

Retrospective analysis of aspirin's role in the severity of COVID-19 pneumonia

Gogtay et al., World Journal of Critical Care Medicine, doi:10.5492/wjccm.v11.i2.92

Retrospective 125 COVID+ hospitalized patients in the USA, showing no significant differences with aspirin prophylaxis.

risk of death, 5.9% higher, RR 1.06, p = 0.87, treatment 12 of 38 (31.6%), control 21 of 87 (24.1%), adjusted, OR converted to RR, multivariable.

risk of mechanical ventilation, 49.8% lower, RR 0.50, p = 0.16, treatment 5 of 38 (13.2%), control 21 of 87 (24.1%), NNT 9.1, adjusted, OR converted to RR, multivariable.

risk of ICU admission, 49.2% lower, RR 0.51, p = 0.41, treatment 9 of 38 (23.7%), control 38 of 87 (43.7%), NNT 5.0, adjusted, OR converted to RR, multivariable.

Gogtay et al., 3/9/2022, retrospective, USA, North America, peer-reviewed, 4 authors, study period March 2020 - April 2020.

The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization

Nimer et al., Bosnian Journal of Basic Medical Sciences, doi:10.17305/bjbms.2021.7009

Retrospective survey based analysis of 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with aspirin prophylaxis.

risk of hospitalization, 3.7% lower, RR 0.96, p = 0.08, treatment 83 of 427 (19.4%), control 136 of 1,721 (7.9%), adjusted, OR converted to RR, multivariable.

risk of severe case, 17.8% higher, RR 1.18, p = 0.28, treatment 98 of 427 (23.0%), control 162 of 1,721 (9.4%), adjusted, OR converted to RR, multivariable.

Nimer et al., 2/28/2022, retrospective, Jordan, Middle East, peer-reviewed, survey, 4 authors, study period March 2021 - July 2021.

Frail Older Adults with Presymptomatic SARS-CoV-2 Infection: Clinical Course and Prognosis

Levy et al., Gerontology, doi:10.1159/000521412

Retrospective 849 COVID-19+ patients in skilled nursing homes, showing lower risk of combined hospitalization/death with aspirin prophylaxis, not reaching statistical significance.

risk of death/hospitalization, 26.0% lower, HR 0.74, p = 0.13, treatment 29 of 159 (18.2%), control 178 of 690 (25.8%), NNT 13, adjusted, multivariable, Cox proportional hazards, day 40.

Levy et al., 1/31/2022, retrospective, Israel, Middle East, peer-reviewed, 10 authors.

A Multimodal Strategy to Reduce the Risk of Hospitalization/death in Ambulatory Patients with COVID-19

de Jesús Ascencio-Montiel et al., Archives of Medical Research, doi:10.1016/j.arcmed.2022.01.002

Retrospective 28,048 COVID+ patients in Mexico, 7,898 receiving a treatment kit including low dose ivermectin, AZ, aspirin, and acetaminophen, shower lower mortality/hospitalization for those receiving the kit. Delivery of the treatment kit was based on availability in the medical units. Adherence is unknown and may be low. Adjusted results are only provided for combined mortality/hospitalization.

risk of death/hospitalization, 59.0% lower, RR 0.41, p < 0.001, treatment 7,898, control 20,150, adjusted, multivariable, primary outcome.

risk of death/hospitalization, 71.0% lower, RR 0.29, p < 0.001, treatment 5,557, control 12,526, adjusted, with phone call followup, multivariable.

risk of death, 15.0% lower, RR 0.85, p = 0.16, treatment 101 of 7,898 (1.3%), control 303 of 20,150 (1.5%), NNT 445, unadjusted, excluded in exclusion analyses: unadjusted results with alternate outcome adjusted results showing significant changes with adjustments.

risk of mechanical ventilation, 9.1% lower, RR 0.91, p = 0.51, treatment 77 of 7,898 (1.0%), control 216 of 20,150 (1.1%), NNT 1031, unadjusted, excluded in exclusion analyses: unadjusted results with alternate outcome adjusted results showing significant changes with adjustments.

risk of hospitalization, 47.6% lower, RR 0.52, p < 0.001, treatment 485 of 7,898 (6.1%), control 2,360 of 20,150 (11.7%), NNT 18, unadjusted, excluded in exclusion analyses: unadjusted results with alternate outcome adjusted results showing significant changes with adjustments.

risk of progression, 41.8% lower, RR 0.58, p < 0.001, treatment 435 of 7,898 (5.5%), control 1,906 of 20,150 (9.5%), NNT 25, unadjusted, ER, excluded in exclusion analyses: unadjusted results with alternate outcome adjusted results showing significant changes with adjustments.

Excluded in meta analysis: combined treatments may contribute more to the effect seen.

de Jesús Ascencio-Montiel et al., 1/24/2022, retrospective, Mexico, North America, peer-reviewed, 10 authors, this trial uses multiple treatments in the treatment arm (combined with AZ, acetaminophen, ivermectin) - results of individual treatments may vary.

A Case-Control of Patients with COVID-19 to Explore the Association of Previous Hospitalisation Use of Medication on the Mortality of COVID-19 Disease: A Propensity Score Matching Analysis

Monserrat Villatoro et al., Pharmaceuticals, doi:10.3390/ph15010078

PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate, and higher mortality with acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol.

risk of death, 31.0% higher, OR 1.31, p = 0.04, RR approximated with OR.

Monserrat Villatoro et al., 1/8/2022, retrospective, propensity score matching, Spain, Europe, peer-reviewed, 18 authors.

Premorbid aspirin use is not associated with lower mortality in older inpatients with SARS-CoV-2 pneumonia

Sullerot et al., GeroScience, doi:10.1007/s11357-021-00499-8

Retrospective 1,047 pneumonia patients in 5 COVID-19 geriatric units in France and Switzerland, significantly higher ICU admission and longer hospital stays with existing aspirin treatment. Numbers in this study appear to be inconsistent, for example the abstract says 147 of 301 aspirin patients died, shown as 34.3%, while Table 1 shows 104 of 301 (34.6%).

risk of death, 10.0% higher, RR 1.10, p = 0.52, treatment 101 of 301 (33.6%), control 224 of 746 (30.0%).

risk of ICU admission, 109.7% higher, RR 2.10, p = 0.007, treatment 22 of 301 (7.3%), control 26 of 746 (3.5%).

hospitalization time, 10.0% higher, relative time 1.10, p = 0.02, treatment 301, control 746.

Sullerot et al., 1/7/2022, retrospective, inverse propensity weighting, multiple countries, multiple regions, peer-reviewed, 15 authors, study period 1 March, 2020 - 31 December, 2020.

Pattern of medication utilization in hospitalized patients with COVID-19 in three District Headquarters Hospitals in the Punjab province of Pakistan

Mustafa et al., Exploratory Research in Clinical and Social Pharmacy, doi:10.1016/j.rcsop.2021.100101

Retrospective 444 hospitalized patients in Pakistan, showing lower mortality with aspirin treatment in unadjusted results, not reaching statistical significance.

risk of death, 44.1% lower, RR 0.56, p = 0.28, treatment 4 of 66 (6.1%), control 41 of 378 (10.8%), NNT 21.

Excluded in after exclusion results of meta analysis: unadjusted results with no group details.

Mustafa et al., 12/29/2021, retrospective, Pakistan, South Asia, peer-reviewed, 7 authors.

A systematic review and meta-analysis on efficacy of low dose aspirin on the management of COVID-19

Banaser et al., International Journal of Medicine in Developing Countries, doi:10.24911/IJMDC.51-1640383699 (meta analysis)

Meta analysis of 8 studies showing significantly lower mortality and mechanical ventilation with low dose aspirin.

risk of death, 49.0% lower, RR 0.51, p < 0.001.

risk of mechanical ventilation, 30.0% lower, RR 0.70, p = 0.006.

Banaser et al., 12/24/2021, peer-reviewed, 5 authors.

Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

RECOVERY Collaborative Group, The Lancet, doi:10.1016/S0140-6736(21)01825-0

RCT 14,892 late stage patients, 7,351 treated with aspirin, showing slightly improved discharge and hospitalization time, and no significant difference for mortality.

Results are limited due to low dose (150mg daily), very late treatment (9 days post symptom onset), and 96% concurrent use of low molecular weight heparin. Greater benefits were seen for non-LMWH patients, and for very late (<= 7 days from onset) vs. extremely late (>7 days) treatment. For more discussion see [twitter.com].

1. twitter.com, https://twitter.com/Covid19Crusher/status/1461272964675031042.

risk of death, 4.0% lower, RR 0.96, p = 0.35, treatment 7,351, control 7,541.

risk of death, 17.0% lower, RR 0.83, p = 0.35, treatment 7,351, control 7,541, non-LMWH.

risk of mechanical ventilation, 5.0% lower, RR 0.95, p = 0.32, treatment 7,351, control 7,541.

risk of no hospital discharge, 5.7% lower, RR 0.94, p = 0.006, treatment 7,351, control 7,541.

risk of no hospital discharge, 16.0% lower, RR 0.84, p = 0.04, treatment 7,351, control 7,541, non-LMWH.

hospitalization time, 11.1% lower, relative time 0.89, treatment 7,351, control 7,541.

RECOVERY et al., 11/18/2021, Randomized Controlled Trial, multiple countries, multiple regions, peer-reviewed, 1 author, study period 1 November, 2020 - 21 March, 2021, average treatment delay 9.0 days.

Antiplatelet therapy and outcome in patients with COVID-19. Results from a multi-center international prospective registry (HOPE-COVID19)

Santoro et al., European Heart Journal, doi:10.1093/eurheartj/ehab724.3002

Retrospective database analysis of 7,824 patients in the HOPE-COVID19 registry, 730 receiving antiplatelet therapy including aspirin, showing lower mortality with treatment. Authors do not provide results restricted to aspirin.

risk of death, 71.0% lower, RR 0.29, p < 0.001, treatment 730, control 7,094, antiplatelet therapy, multivariable.

Santoro et al., 10/14/2021, retrospective, multiple countries, multiple regions, peer-reviewed, 6 authors.

Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19

Connors et al., JAMA, doi:10.1001/jama.2021.1727283

Early terminated RCT with 164 aspirin and 164 control patients in the USA with very few events, showing no significant difference with aspirin treatment for the combined endpoint of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, and hospitalization for cardiovascular or pulmonary indication. There was no mortality and no major bleeding events among participants that started treatment (there was one ITT placebo death). ACTIV-4B. NCT04498273.

risk of hospitalization, 67.3% lower, RR 0.33, p = 0.49, treatment 0 of 144 (0.0%), control 1 of 136 (0.7%), NNT 136, relative risk is not 0 because of continuity correction due to zero events, hospitalization for cardiovascular or pulmonary indication, suspected, started treatment.

risk of progression, 19.0% lower, RR 0.81, p = 0.78, treatment 6 of 144 (4.2%), control 7 of 136 (5.1%), NNT 102, acute medical event, suspected, started treatment.

risk of progression, 5.6% lower, RR 0.94, p = 1.00, treatment 1 of 144 (0.7%), control 1 of 136 (0.7%), NNT 2448, combined endpoint of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, and hospitalization for cardiovascular or pulmonary indication, suspected, started treatment, primary outcome.

Connors et al., 10/11/2021, Double Blind Randomized Controlled Trial, placebo-controlled, USA, North America, peer-reviewed, 27 authors, trial NCT04498273.

Prognostic factors at admission on patients with cancer and COVID-19: Analysis of HOPE registry data

Pérez-Segura et al., Medicina Clínica, doi:10.1016/j.medcle.2021.02.010

Retrospective 770 COVID-19 patients with cancer, showing increased mortality with aspirin use in unadjusted results.

risk of death, 49.1% higher, RR 1.49, p < 0.001, treatment 66 of 155 (42.6%), control 183 of 608 (30.1%), OR converted to RR.

Pérez-Segura et al., 10/4/2021, retrospective, multiple countries, multiple regions, peer-reviewed, 23 authors.

Pre-admission acetylsalicylic acid therapy and impact on in-hospital outcome in COVID-19 patients: The ASA-CARE study

Sisinni et al., International Journal of Cardiology, doi:10.1016/j.ijcard.2021.09.058

Retrospective 984 COVID-19 patients, 253 taking aspirin prior to admission, showing lower risk of respiratory support upgrade with treatment.

risk of death, 7.1% higher, RR 1.07, p = 0.65, treatment 93 of 253 (36.8%), control 251 of 731 (34.3%).

risk of death or respiratory support upgrade, 30.3% lower, RR 0.70, p = 0.01, treatment 253, control 731, multivariate.

Sisinni et al., 10/4/2021, retrospective, Italy, Europe, peer-reviewed, 18 authors, average treatment delay 7.0 days.

Clinical Predictors of Mortality and Critical Illness in Patients with COVID-19 Pneumonia

Basheer et al., Metabolites, doi:10.3390/metabo11100679

Retrospective 390 hospitalized patients in Israel, showing higher risk of mortality with prior aspirin use. Details of the analysis are not provided.

risk of death, 13.0% higher, RR 1.13, p < 0.001, treatment 45 of 140 (32.1%), control 29 of 250 (11.6%), adjusted, OR converted to RR, group sizes approximated (only percentages provided).

Basheer et al., 10/2/2021, retrospective, Israel, Middle East, peer-reviewed, 4 authors.

Treatments Associated with Lower Mortality among Critically Ill COVID-19 Patients: A Retrospective Cohort Study

Zhao et al., Anesthesiology, doi:10.1097/ALN.0000000000003999

Retrospective 2,070 hospitalized patients in the USA, showing lower mortality with aspirin treatment.

risk of death, 43.0% lower, HR 0.57, p < 0.001, treatment 121 of 473 (25.6%), control 140 of 473 (29.6%), adjusted, PSM.

risk of death, 28.0% lower, HR 0.72, p = 0.03, treatment 473, control 1,597, adjusted, multivariable.

Zhao et al., 10/1/2021, retrospective, USA, North America, peer-reviewed, 6 authors.

Aspirin Is Related to Worse Clinical Outcomes of COVID-19

Kim et al., Medicina, doi:10.3390/medicina57090931

Retrospective database analysis of 22,660 patients tested for COVID-19 in South Korea. There was no significant difference in cases according to aspirin use. Aspirin use before COVID-19 was related to an increased death rate and aspirin use after COVID-19 was related to a higher risk of oxygen therapy.

risk of death, 700.0% higher, RR 8.00, p = 0.03, treatment 6 of 15 (40.0%), control 1 of 20 (5.0%), PSM, prior aspirin use.

risk of mechanical ventilation, 433.3% higher, RR 5.33, p = 0.14, treatment 4 of 15 (26.7%), control 1 of 20 (5.0%), PSM, prior aspirin use.

risk of ICU admission, 433.3% higher, RR 5.33, p = 0.14, treatment 4 of 15 (26.7%), control 1 of 20 (5.0%), PSM, prior aspirin use.

risk of case, 33.4% lower, RR 0.67, p = 0.29, treatment 15 of 136 (11.0%), control 20 of 136 (14.7%), NNT 27, adjusted, OR converted to RR, PSM, logistic regression, prior aspirin use.

risk of death, 33.7% lower, RR 0.66, p = 0.22, treatment 14 of 124 (11.3%), control 23 of 135 (17.0%), NNT 17, PSM, aspirin treatment after diagnosis.

risk of mechanical ventilation, 102.2% higher, RR 2.02, p = 0.16, treatment 13 of 124 (10.5%), control 7 of 135 (5.2%), PSM, aspirin treatment after diagnosis.

risk of ICU admission, 90.5% higher, RR 1.91, p = 0.36, treatment 7 of 124 (5.6%), control 4 of 135 (3.0%), PSM, aspirin treatment after diagnosis.

Kim et al., 9/4/2021, retrospective, propensity score matching, South Korea, Asia, peer-reviewed, 7 authors.

Evaluation of Low-Dose Aspirin use among Critically Ill Patients with COVID-19: A Multicenter Propensity Score Matched Study

Al Harthi et al., Journal of Intensive Care Medicine, doi:10.1177/08850666221093229

Retrospective 1,033 critical condition patients, showing lower in-hospital mortality with aspirin in PSM analysis. Patients receiving aspirin also had a higher risk of significant bleeding, although not reaching statistical significance. Authors note that the use of aspirin during an ICU stay should be tailored to each patient.

risk of death, 27.0% lower, HR 0.73, p = 0.03, treatment 98 of 176 (55.7%), control 107 of 173 (61.8%), adjusted, in-hospital mortality, multivariable Cox proportional hazards.

risk of death, 14.0% lower, HR 0.86, p = 0.30, treatment 95 of 176 (54.0%), control 97 of 175 (55.4%), adjusted, day 30, multivariable Cox proportional hazards.

Al Harthi et al., 9/3/2021, retrospective, propensity score matching, Saudi Arabia, Middle East, peer-reviewed, 21 authors.

Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience

Karruli et al., Microbial Drug Resistance, doi:10.1089/mdr.2020.0489

Retrospective 32 ICU patients showing lower mortality with aspirin treatment, without statistical significance.

risk of death, 46.3% lower, RR 0.54, p = 0.63, treatment 1 of 5 (20.0%), control 22 of 27 (81.5%), NNT 1.6, adjusted, OR converted to RR, multivariable.

Karruli et al., 9/1/2021, retrospective, Italy, Europe, peer-reviewed, 13 authors, study period March 2020 - May 2020.

Association of Pre-Hospital Antiplatelet Therapy with Survival in Patients Hospitalized with COVID-19: A Propensity Score-Matched Analysis

Chow et al., Journal of Thrombosis and Haemostasis, doi:10.1111/jth.15517

PSM retrospective 6,781 hospitalized patients ≥50 years old in the USA who were on pre-hospital antiplatelet therapy (84% aspirin), and 10,566 matched controls, showing lower mortality with treatment.

risk of death, 19.0% lower, HR 0.81, p < 0.005, treatment 1,280 of 6,781 (18.9%), control 2,271 of 10,566 (21.5%), NNT 38, adjusted, Kaplan Meier.

risk of mechanical ventilation, 2.8% lower, HR 0.97, p = 0.21, treatment 2,122 of 6,781 (31.3%), control 3,403 of 10,566 (32.2%), NNT 109.

Chow et al., 8/29/2021, retrospective, propensity score matching, USA, North America, peer-reviewed, 12 authors.

Sex Differences in Association Between Anti-Hypertensive Medications and Risk of COVID-19 in Middle-Aged and Older Adults

Ma et al., Drugs & Aging, doi:10.1007/s40266-021-00886-y

UK Biobank retrospective 77,271 patients aged 50-86, showing no significant differences with aspirin use. Matching lead to different results for the gender vs. overall analysis, for example the overall result for cases was OR 1.07, however both gender results are lower OR 0.97 and 1.02.

risk of death, 9.0% lower, OR 0.91, p = 0.12, treatment 12,471, control 64,750, RR approximated with OR.

risk of hospitalization, 2.0% lower, OR 0.98, p = 0.47, treatment 12,471, control 64,750, RR approximated with OR.

risk of symptomatic case, 9.0% higher, OR 1.09, p = 0.18, treatment 12,471, control 64,750, RR approximated with OR.

risk of case, 7.0% higher, OR 1.07, p = 0.09, treatment 12,471, control 64,750, RR approximated with OR.

Ma et al., 8/18/2021, retrospective, propensity score matching, United Kingdom, Europe, peer-reviewed, 9 authors.

Effect of aspirin on coronavirus disease 2019

Son et al., Medicine, doi:10.1097/MD.0000000000026670

PSM retrospective case control study in South Korea, showing a trend towards lower mortality, but no significant differences with aspirin use.

risk of death, 24.0% lower, OR 0.76, p = 0.52, treatment 37 of 128 (28.9%) cases, 31 of 128 (24.2%) controls, case control OR, group 1, model 2 (most data in group and adjustments).

risk of progression, 7.0% higher, OR 1.07, p = 0.80, treatment 77 of 339 (22.7%) cases, 58 of 339 (17.1%) controls, case control OR, complications, group 1, model 2 (most data in group and adjustments).

risk of case, 11.0% higher, OR 1.11, p = 0.21, treatment 313 of 3,825 (8.2%) cases, 617 of 7,650 (8.1%) controls, case control OR, group 1, PSM 1, model 2 (most data in group and adjustments).

Son et al., 7/30/2021, retrospective, propensity score matching, South Korea, Asia, peer-reviewed, 6 authors.

Acetylsalicylic Acid Compared with Enoxaparin for the Prevention of Thrombosis and Mechanical Ventilation in COVID-19 Patients: A Retrospective Cohort Study

Abdelwahab et al., Clinical Drug Investigation, doi:10.1007/s40261-021-01061-2

Retrospective 225 hospitalized patients in Egypt, showing significantly lower thromboembolic events with aspirin treatment, but no significant difference in the need for mechanical ventilation.

risk of mechanical ventilation, 7.8% higher, RR 1.08, p = 0.93, treatment 11 of 31 (35.5%), control 6 of 36 (16.7%), adjusted, OR converted to RR.

Abdelwahab et al., 7/30/2021, retrospective, Egypt, Africa, peer-reviewed, 17 authors.

Association of In-hospital Use of Statins, Aspirin, and Renin-Angiotensin-Aldosterone Inhibitors with Mortality and ICU Admission Due to COVID-19

Vahedian-Azimi et al., Identification of Biomarkers, New Treatments, and Vaccines for COVID-19, doi:10.1007/978-3-030-71697-4_17

Retrospective 587 COVID+ hospitalized patients in Iran, showing no significant differences in outcomes with aspirin treatment.

risk of death, 21.9% lower, RR 0.78, p = 0.56, treatment 13 of 337 (3.9%), control 28 of 250 (11.2%), adjusted, OR converted to RR, multivariable, primary outcome.

risk of ICU admission, 10.5% higher, RR 1.10, p = 0.67, treatment 36 of 337 (10.7%), control 44 of 250 (17.6%), adjusted, OR converted to RR, multivariable.

Vahedian-Azimi et al., 7/20/2021, retrospective, Iran, Middle East, peer-reviewed, 9 authors.

Oral corticoid, aspirin, anticoagulant, colchicine, and furosemide to improve the outcome of hospitalized COVID-19 patients - the COCAA-COLA cohort study

Kevorkian et al., Journal of Infection, doi:10.1016/j.jinf.2021.02.008

Observational study in France with 28 hospitalized patients treated with prednisone/furosemide/colchicine/salicylate/direct anti-Xa inhibitor, and 40 control patients, showing lower combined mortality, ventilation, or high-flow oxygen therapy with treatment.

risk of mortality, ventilation, or high-flow oxygen therapy, 95.7% lower, OR 0.04, p < 0.001, treatment 28, control 40, adjusted, multivariable, RR approximated with OR.

Excluded in meta analysis: combined treatments may contribute more to the effect seen.

Kevorkian et al., 6/30/2021, retrospective, France, Europe, peer-reviewed, 11 authors, study period 9 January, 2020 - 30 November, 2020, this trial uses multiple treatments in the treatment arm (combined with prednisone, furosemide, salicylate, direct anti-Xa inhibitor) - results of individual treatments may vary.

Incidence and Mortality Associated with Cardiovascular Medication among Hypertensive COVID-19 Patients in South Korea

Oh et al., Yonsei Medical Journal, doi:10.3349/ymj.2021.62.7.577

Retrospective database analysis of 328,374 adults in South Korea, showing lower risk of COVID-19 cases with aspirin use, but no difference in mortality for COVID-19 patients.

risk of death, 1.0% lower, OR 0.99, p = 0.95, adjusted, multivariable, RR approximated with OR.

risk of case, 12.0% lower, RR 0.88, p = 0.04, adjusted, OR converted to RR, multivariable, control prevalance approximated with overall prevalence.

Oh et al., 6/17/2021, retrospective, database analysis, South Korea, Asia, peer-reviewed, 4 authors.

Case Characteristics, Clinical Data, And Outcomes of Hospitalized COVID-19 Patients In Qom Province, Iran: A Prospective Cohort Study

Pourhoseingholi et al., Research Square, doi:10.21203/rs.3.rs-365321/v2 (Preprint)

Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing higher mortality with aspirin treatment. IR.MUQ.REC.1399.013.

risk of death, 32.0% higher, HR 1.32, p = 0.04, treatment 71 of 290 (24.5%), control 268 of 2,178 (12.3%), adjusted, multivariable, Cox proportional hazards.

Pourhoseingholi et al., 5/26/2021, prospective, Iran, Middle East, preprint, mean age 57.9, 11 authors, study period 2 February, 2020 - 20 July, 2020, average treatment delay 7.4 days.

Pre-hospital antiplatelet medication use on COVID-19 disease severity

Pan et al., Heart & Lung, doi:10.1016/j.hrtlng.2021.04.010

Retrospective 762 COVID+ hospitalized patients in the USA, 239 on antiplatelet medication (199 aspirin), showing no significant differences in outcomes.

risk of death, 13.0% higher, OR 1.13, p = 0.63, treatment 239, control 523, adjusted, MOS 6 vs. <6, multivariable, RR approximated with OR.

risk of death/intubation, 2.0% higher, OR 1.02, p = 0.93, treatment 239, control 523, adjusted, MOS 5+ vs. <5, multivariable, RR approximated with OR.

Pan et al., 5/26/2021, retrospective, USA, North America, peer-reviewed, 11 authors, study period 1 March, 2020 - 9 April, 2020.

Effect of aspirin on short-term outcomes in hospitalized patients with COVID-19

Sahai et al., Vascular Medicine, doi:10.1177/1358863X211012754

PSM retrospective 1,994 PCR+ patients in the USA, not showing a significant difference in mortality with aspirin treatment.

risk of death, 13.2% lower, RR 0.87, p = 0.53, treatment 33 of 248 (13.3%), control 38 of 248 (15.3%), NNT 50.

Sahai et al., 5/19/2021, retrospective, propensity score matching, USA, North America, peer-reviewed, 18 authors.

Epidemiology, outcomes, and utilization of intensive care unit resources for critically ill COVID-19 patients in Libya: A prospective multi-center cohort study

Elhadi et al., PLOS ONE, doi:10.1371/journal.pone.0251085

Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.

risk of death, 9.7% lower, RR 0.90, p = 0.50, treatment 22 of 40 (55.0%), control 259 of 425 (60.9%), NNT 17.

Excluded in after exclusion results of meta analysis: unadjusted results with no group details.

Elhadi et al., 4/30/2021, prospective, Libya, Africa, peer-reviewed, 21 authors, study period 29 May, 2020 - 30 December, 2020.

Decreased in-hospital mortality associated with aspirin administration in hospitalized patients due to severe COVID-19

Haji Aghajani et al., Journal of Medical Virology, doi:10.1002/jmv.27053

Retrospective 991 hospitalized patients in Iran, showing lower mortality with aspirin treatment.

risk of death, 24.7% lower, HR 0.75, p = 0.04, treatment 336, control 655, adjusted, Cox proportional hazards, RR approximated with OR.

Haji Aghajani et al., 4/29/2021, retrospective, Iran, Middle East, peer-reviewed, 7 authors.

3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study

Mulhem et al., BMJ Open, doi:10.1136/bmjopen-2020-042042

Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.

risk of death, 13.9% higher, RR 1.14, p = 0.21, treatment 300 of 1,354 (22.2%), control 216 of 1,865 (11.6%), adjusted, OR converted to RR, Table S1, logistic regression.

Excluded in after exclusion results of meta analysis: substantial unadjusted confounding by indication likely, substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.

Mulhem et al., 4/7/2021, retrospective, database analysis, USA, North America, peer-reviewed, 3 authors.

Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019

Chow et al., Anesthesia & Analgesia, doi:10.1213/ANE.0000000000005292

Retrospective 412 hospitalized patients, 98 treated with aspirin, showing lower mortality, ventilation, and ICU admission with treatment.

risk of death, 47.0% lower, HR 0.53, p = 0.02, treatment 26 of 98 (26.5%), control 73 of 314 (23.2%), adjusted, Cox proportional hazards.

risk of mechanical ventilation, 44.0% lower, HR 0.56, p = 0.007, treatment 35 of 98 (35.7%), control 152 of 314 (48.4%), NNT 7.9, adjusted, Cox proportional hazards.

risk of ICU admission, 43.0% lower, HR 0.57, p = 0.007, treatment 38 of 98 (38.8%), control 160 of 314 (51.0%), NNT 8.2, adjusted, Cox proportional hazards.

Chow et al., 4/1/2021, retrospective, USA, North America, peer-reviewed, 38 authors.

Real-world evidence for improved outcomes with histamine antagonists and aspirin in 22,560 COVID-19 patients

Mura et al., Signal Transduction and Targeted Therapy, doi:10.1038/s41392-021-00689-y (preprint 3/31/2021)

PSM retrospective TriNetX database analysis of 1,379 severe COVID-19 patients requiring respiratory support, showing lower mortality with aspirin (not reaching statistical significance) and famotidine, and improved results from the combination of both.

risk of death, 15.4% lower, RR 0.85, p = 0.08, treatment 527, control 527, OR converted to RR, aspirin only, control prevalence approximated with treatment prevalence, propensity score matching.

risk of death, 37.3% lower, RR 0.63, p = 0.001, treatment 305, control 305, OR converted to RR, famotidine and aspirin, control prevalence approximated with treatment prevalence, propensity score matching.

Mura et al., 3/31/2021, retrospective, database analysis, multiple countries, multiple regions, peer-reviewed, 6 authors.

The use of aspirin for primary prevention of cardiovascular disease is associated with a lower likelihood of COVID-19 infection

Merzon et al., The FEBS Journal, doi:10.1111/febs.15784

Retrospective 10,477 patients in Israel, showing lower risk of COVID-19 cases with existing aspiring use.

risk of case, 27.6% lower, RR 0.72, p = 0.04, treatment 73 of 1,621 (4.5%), control 589 of 8,856 (6.7%), NNT 47, adjusted, OR converted to RR.

risk of death, 62.4% lower, RR 0.38, p = 0.51, treatment 1 of 21 (4.8%), control 6 of 91 (6.6%), adjusted, OR converted to RR.

time to viral-, 9.6% lower, relative time 0.90, p = 0.045, treatment 73, control 589, time to 2nd negative test.

time to viral-, 14.8% lower, relative time 0.85, p = 0.005, treatment 73, control 589, time to 1st negative test.

Merzon et al., 2/23/2021, retrospective, Israel, Middle East, peer-reviewed, 8 authors.

Effect of low-dose aspirin on mortality and viral duration of the hospitalized adults with COVID-19

Liu et al., Medicine, doi:10.1097/MD.0000000000024544

Retrospective PSM analysis of 232 hospitalized patients, 28 treated with aspirin, showing lower mortality with treatment. There was no significant difference in viral clearance.

risk of death, 75.0% lower, HR 0.25, p = 0.03, treatment 2 of 28 (7.1%), control 11 of 204 (5.4%), adjusted, 60 days, KM, PSM.

risk of death, 81.0% lower, HR 0.19, p = 0.02, treatment 1 of 28 (3.6%), control 9 of 204 (4.4%), adjusted, 30 days, KM, PSM.

time to viral-, 1.9% higher, relative time 1.02, p = 0.94, treatment 24, control 24, PSM.

Liu et al., 2/12/2021, retrospective, propensity score matching, China, Asia, peer-reviewed, 8 authors.

Association of mortality and aspirin prescription for COVID-19 patients at the Veterans Health Administration

Osborne et al., PloS ONE, doi:10.1371/journal.pone.0246825

Retrospective PSM analysis of pre-existing aspirin use in the USA, showing lower mortality with treatment.

risk of death, 59.4% lower, RR 0.41, p < 0.001, treatment 272 of 6,300 (4.3%), control 661 of 6,300 (10.5%), NNT 16, OR converted to RR, 30 days, PSM.

risk of death, 60.5% lower, RR 0.40, p < 0.001, treatment 170 of 6,814 (2.5%), control 427 of 6,814 (6.3%), NNT 27, OR converted to RR, 14 days, PSM.

Osborne et al., 2/11/2021, retrospective, propensity score matching, USA, North America, peer-reviewed, 6 authors.

Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: A propensity score-matched analysis

Meizlish et al., American Journal of Hematology, doi:10.1002/ajh.26102

Retrospective 638 matched hospitalized patients in the USA, 319 treated with aspirin, showing lower mortality with treatment.

risk of death, 47.8% lower, HR 0.52, p = 0.004, treatment 319, control 319, PSM.

Meizlish et al., 1/21/2021, retrospective, propensity score matching, USA, North America, peer-reviewed, 22 authors.

Mortality and pre-hospitalization use of low-dose aspirin in COVID-19 patients with coronary artery disease

Yuan et al., Journal of Cellular and Molecular Medicine, doi:10.1111/jcmm.16198

Retrospective 183 hospitalized patients in China, 52 taking low-dose aspirin prior to hospitalization, showing no significant difference with treatment.

risk of death, 4.4% lower, RR 0.96, p = 0.89, treatment 11 of 52 (21.2%), control 29 of 131 (22.1%), NNT 102, OR converted to RR, mutivariate.

Yuan et al., 12/18/2020, retrospective, China, Asia, peer-reviewed, 6 authors.

Admission Rothman Index, Aspirin, and Intermediate Dose Anticoagulation Effects on Outcomes in COVID-19: A Multi-Site Propensity Matched Analysis

Goshua et al., Blood, doi:10.1182/blood-2020-143349

PSM retrospective 2,785 hospitalized patients in the USA, showing lower mortality and higher ventilation and ICU admission with aspirin treatment.

risk of death, 35.0% lower, OR 0.65, p = 0.04, treatment 319, control 319, propensity score matching, RR approximated with OR.

risk of mechanical ventilation, 49.0% higher, OR 1.49, p = 0.04, treatment 319, control 319, propensity score matching, RR approximated with OR.

risk of ICU admission, 45.0% higher, OR 1.45, p = 0.02, treatment 319, control 319, propensity score matching, RR approximated with OR.

Goshua et al., 11/5/2020, retrospective, USA, North America, peer-reviewed, 15 authors.

Beneficial effect of low dose aspirin (Acetyl salicylic acid) in adult Covid-19 patients: a retrospective observational study in Bangladesh

Husain et al., ResearchGate, doi:10.13140/RG.2.2.26038.93762/2 (Preprint)

Retrospective 42 patients in Bangladesh, 11 treated with aspirin, showing fewer complications with treatment.

risk of death, 80.3% lower, RR 0.20, p = 0.55, treatment 0 of 11 (0.0%), control 3 of 31 (9.7%), NNT 10, relative risk is not 0 because of continuity correction due to zero events.

risk of no recovery, 64.8% lower, RR 0.35, p = 0.40, treatment 1 of 11 (9.1%), control 8 of 31 (25.8%), NNT 6.0.

complications, 95.8% lower, RR 0.04, p = 0.001, treatment 0 of 11 (0.0%), control 17 of 31 (54.8%), NNT 1.8, relative risk is not 0 because of continuity correction due to zero events.

Husain et al., 10/31/2020, retrospective, Bangladesh, South Asia, preprint, 4 authors.

Mortality Risk Factors among Hospitalized COVID-19 Patients in a Major Referral Center in Iran

Alamdari et al., Tohoku J. Exp. Med., 2020, 252, 73-84, doi:10.1620/tjem.252.73

Retrospective 459 patients in Iran, 53 treated with aspirin, showing no significant difference with treatment.

risk of death, 27.7% higher, RR 1.28, p = 0.52, treatment 9 of 53 (17.0%), control 54 of 406 (13.3%).

Excluded in after exclusion results of meta analysis: substantial unadjusted confounding by indication likely.

Alamdari et al., 9/9/2020, retrospective, Iran, Middle East, peer-reviewed, 14 authors, average treatment delay 5.72 days.

A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward

Wang et al., Journal of Hematology & Oncology, doi:10.1186/s13045-020-00934-x

Retrospective 58 multiple myeloma COVID-19 patients in the USA, showing no significant difference with aspirin treatment.

risk of death, 57.7% lower, RR 0.42, p = 0.43, treatment 1 of 9 (11.1%), control 13 of 49 (26.5%), NNT 6.5, OR converted to RR.

Wang et al., 7/14/2020, retrospective, USA, North America, peer-reviewed, 13 authors.

Association of previous medications with the risk of COVID-19: a nationwide claims-based study from South Korea

Huh et al., medRxiv, doi:10.1101/2020.05.04.20089904 (Preprint)

Retrospective database analysis of 65,149 in South Korea, showing significantly lower cases with existing aspirin treatment. The journal version of this paper does not present the aspirin results (only combined results for NSAIDs).

risk of case, 71.0% lower, RR 0.29, p = 0.001, treatment 8 of 543 (1.5%), control 5,164 of 64,606 (8.0%), adjusted, multivariable.

Huh et al., 5/4/2020, retrospective, database analysis, South Korea, Asia, preprint, 10 authors.

Antiandrogens	(meta)	Lactoferrin	(meta)
Aspirin	(meta)	Melatonin	(meta)
Bamlaniv../e..	(meta)	Metformin	(meta)
Bebtelovimab	(meta)	Molnupiravir	(meta)
Bromhexine	(meta)	N-acetylcys..	(meta)
Budesonide	(meta)	Nigella Sativa	(meta)
Cannabidiol	(meta)	Nitazoxanide	(meta)
Casirivimab/i..	(meta)	Paxlovid	(meta)
Colchicine	(meta)	Peg.. Lambda	(meta)
Conv. Plasma	(meta)	Povidone-Iod..	(meta)
Curcumin	(meta)	Probiotics	(meta)
Diet	(meta)	Proxalutamide	(meta)
Ensitrelvir	(meta)	Quercetin	(meta)
Ensovibep	(meta)	Remdesivir	(meta)
Exercise	(meta)	Sleep	(meta)
Famotidine	(meta)	Sotrovimab	(meta)
Favipiravir	(meta)	Tixagev../c..	(meta)
Fluvoxamine	(meta)	Vitamin A	(meta)
Hydroxychlor..	(meta)	Vitamin C	(meta)
Iota-carragee..	(meta)	Vitamin D	(meta)
Ivermectin	(meta)	Zinc	(meta)

Other Treatments		Global Adoption