Aspirin is not a recommended treatment for COVID-19. The largest and most rigorous randomized trial to date, involving nearly 15,000 hospitalized patients, found that aspirin did not reduce the risk of death within 28 days. While earlier observational studies generated genuine excitement about aspirin’s potential, the controlled evidence has not supported routine use, and major guidelines now advise against adding it for hospitalized COVID-19 patients. The story is more nuanced than a flat “no,” though, particularly when it comes to people who already take aspirin for other reasons and the emerging, unproven theory that aspirin could play a role in treating long COVID.
Why Aspirin Seemed Like a Reasonable Bet
COVID-19 turned out to be far more than a respiratory infection. Severe cases trigger widespread inflammation and an unusual tendency toward blood clots, both in veins and in the tiny capillaries of the lungs. Aspirin attacks both of those problems at once. It blocks enzymes called COX-1 and COX-2, which are involved in producing inflammation-driving molecules. Its breakdown product, salicylic acid, also dampens a key inflammation switch called NF-κB, reducing the production of inflammatory signaling proteins that can spiral out of control during severe COVID-19.1PubMed Central. Aspirin as an Adjunctive Pharmacologic Therapy Option for COVID-19: Anti-Inflammatory, Antithrombotic, and Antiviral Effects All in One Agent On the clotting side, aspirin is one of the oldest and cheapest antiplatelet drugs available, and COVID-19 patients were showing up with hyperactive platelets and dangerous clots at rates that alarmed clinicians early in the pandemic.
This dual action made aspirin an attractive candidate. It was already widely available, dirt cheap, and had a safety profile that had been studied for over a century. Researchers around the world launched observational studies and, eventually, randomized trials to find out whether this familiar medicine could save lives in an unfamiliar disease.
What the RECOVERY Trial Found
The definitive answer came from the RECOVERY trial, a massive UK-based platform trial that randomized 7,351 hospitalized COVID-19 patients to receive aspirin (150 mg daily) and 7,541 to receive usual care alone. The result was clear: about 17% of patients died in both groups within 28 days, with no statistically meaningful difference between them.2PubMed Central. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial Aspirin also failed to reduce the combined risk of needing a ventilator or dying among patients who were not already on mechanical ventilation when they enrolled.
There were two small, offsetting effects worth noting. Patients on aspirin were slightly more likely to be discharged alive within 28 days, with a median hospital stay one day shorter. And aspirin did reduce thrombotic events, from about 5.3% to 4.6%. But it also increased major bleeding events, from roughly 1.0% to 1.6%.3The Lancet. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial In practical terms, the clot reduction and the bleeding increase roughly cancelled each other out. The trial’s conclusion was unambiguous: aspirin does not meaningfully improve outcomes for hospitalized COVID-19 patients.
Why Observational Studies Told a More Optimistic Story
Before the RECOVERY results appeared, a wave of observational studies had suggested aspirin might help. A meta-analysis pooling fourteen observational studies covering more than 164,000 COVID-19 patients reported a reduced risk of in-hospital mortality associated with aspirin use.4American Heart Journal Plus: Cardiology Research and Practice. Aspirin use is associated with decreased inpatient mortality in patients with COVID-19: A meta-analysis Another systematic review found roughly a 16% decrease in in-hospital mortality among aspirin users.5PubMed Central. All-cause and in-hospital mortality after aspirin use in patients hospitalized with COVID-19: a systematic review and meta-analysis
These numbers looked encouraging, but they came with a fundamental problem. Observational studies cannot easily separate the effect of aspirin itself from the characteristics of the people who take it. Patients on aspirin before admission often had cardiovascular conditions that prompted closer monitoring and more aggressive general care. Some of them were also already on other medications, like statins or blood pressure drugs, that might confer independent benefits. When the RECOVERY trial stripped away those confounders by randomly assigning aspirin, the apparent benefit vanished. This is a textbook example of why randomized evidence outranks observational data, and it is the main reason guidelines shifted against aspirin as a COVID-19 treatment.
The Bleeding Trade-Off
One of the central concerns with any antiplatelet or anticoagulant therapy in a critically ill population is bleeding. COVID-19 patients often receive blood thinners like heparin as part of standard care, and layering aspirin on top raises the stakes. The RECOVERY trial documented a small but real increase in major bleeding when aspirin was added.
Interestingly, at least one large observational study painted a more reassuring picture. A study of patients with moderate COVID-19 who received early aspirin found no significant increase in gastrointestinal hemorrhage, cerebral hemorrhage, or need for blood transfusion compared to those who did not receive aspirin.6JAMA Network Open. Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19 A separate propensity-matched study found that antiplatelet agents were not associated with increased gastrointestinal bleeding risk in hospitalized COVID-19 patients.7PubMed. Gastrointestinal bleeding in hospitalized COVID-19 patients: a propensity score matched cohort study The discrepancy likely comes down to patient severity, concurrent medications, and study design. The bottom line is that while aspirin does not seem to cause catastrophic bleeding in most COVID-19 patients, it does push the needle in the wrong direction enough to matter when there is no offsetting mortality benefit.
What About People Already Taking Aspirin?
A different question from “should aspirin be started for COVID-19” is “what happens to people who were already on aspirin when they got infected?” Many patients with heart disease, a history of stroke, or peripheral artery disease take daily low-dose aspirin as a long-standing prescription. Several studies looked at this group specifically.
One Italian multicenter study found that patients who were already on aspirin before admission had a lower probability of reaching a combined endpoint of worsening respiratory failure and other poor outcomes, even after adjusting for other factors.8PubMed Central. Pre-admission acetylsalicylic acid therapy and impact on in-hospital outcome in COVID-19 patients: The ASA-CARE study However, a separate analysis found that prehospitalization antiplatelet agents had no significant impact on in-hospital mortality when the model was adjusted for other conditions the patients had.9Archives of Cardiovascular Diseases. Platelet activation and coronavirus disease 2019 mortality: Insights from coagulopathy, antiplatelet therapy and inflammation A smaller retrospective study found that aspirin users were less likely to need ICU-level care, but found no significant difference in survival or the need for mechanical ventilation.10PubMed Central. Retrospective analysis of aspirin’s role in the severity of COVID-19 pneumonia
The evidence here is mixed and comes entirely from observational studies, which makes it hard to draw firm conclusions. What is clear is that no major guideline recommends stopping aspirin in COVID-19 patients who were already taking it for a cardiovascular indication. The original reason for the prescription still stands, and abruptly discontinuing it could introduce its own risks.
What the Guidelines Actually Recommend
The International Society on Thrombosis and Haemostasis issued guidelines that give a strong recommendation for prophylactic-dose heparin (either low-molecular-weight heparin or unfractionated heparin) in non-critically ill hospitalized COVID-19 patients. For select patients in this group, therapeutic-dose heparin is preferred over prophylactic dose. But the same guidelines specifically recommend against adding an antiplatelet agent like aspirin.11PubMed Central. ISTH guidelines for antithrombotic treatment in COVID-19 The reasoning is straightforward: heparin-based anticoagulation addresses COVID-19’s clotting problems more effectively, and adding aspirin introduces bleeding risk without a proven mortality benefit.
This does not mean aspirin has zero role in a hospitalized COVID-19 patient’s medication list. Some patients need aspirin for reasons that predate COVID, like a recent coronary stent, and those patients continue it. The guideline applies to starting aspirin as a treatment for the virus itself.
When Aspirin Is Combined With Anticoagulants
One area where the data is more provocative involves combination therapy. A propensity score-matched analysis from the international HOPE-COVID-19 registry found that patients who received both prophylactic anticoagulation and aspirin had lower in-hospital mortality than those on prophylactic anticoagulation alone (roughly 15% versus 21%), and aspirin was independently associated with lower mortality risk even after adjusting for age, sex, and major comorbidities.12PubMed Central. Aspirin Therapy on Prophylactic Anticoagulation for Patients Hospitalized With COVID-19: A Propensity Score-Matched Cohort Analysis of the HOPE-COVID-19 Registry
This is observational evidence, not a randomized trial, so the usual caveats apply. Patients who received both drugs may have differed from those who received anticoagulation alone in ways the statistical matching could not fully capture. Still, the finding is large enough to keep the question alive. No major randomized trial has yet tested aspirin specifically as an add-on to anticoagulation in COVID-19, so this remains an open question rather than a settled one.
Aspirin Resistance in COVID-19 Patients
Even when aspirin is given, it does not always work as expected. COVID-19 appears to make platelets resistant to aspirin’s effects in a substantial number of patients. In one study of 41 COVID-19 patients, among the 14 who were already on aspirin therapy, over half showed high on-treatment platelet reactivity, meaning their platelets were still hyperactive despite the drug.13PubMed Central. Bedside thromboelastography to rapidly assess the pharmacodynamic response of anticoagulants and aspirin in COVID-19: evidence of inadequate therapy in a predominantly minority population This phenomenon, sometimes called aspirin resistance, is not unique to COVID-19 but appears to be more common in it. The intense inflammatory state of severe COVID-19 may drive platelet activation through pathways that aspirin simply does not block.
This finding has practical implications. If more than half of severely ill patients are not even responding to aspirin pharmacologically, it helps explain why the drug failed to improve mortality in randomized trials. It also raises questions about whether higher doses or alternative antiplatelet agents might be more effective, though neither approach has been validated in large trials.
Aspirin and Long COVID
One of the more speculative but intriguing areas involves long COVID. Researchers have identified persistent amyloid fibrin microclots in the blood of people with long COVID. These tiny, abnormal clots resist the body’s normal breakdown processes and may block capillaries, potentially explaining symptoms like fatigue, brain fog, and exercise intolerance that persist months after the acute infection.14PubMed Central. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications Platelet hyperactivation accompanies these microclots in many patients.15PubMed Central. Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC)
A group of researchers has proposed a “triple anticoagulant” regimen for long COVID that includes low-dose aspirin combined with another antiplatelet drug (clopidogrel) and a direct oral anticoagulant, along with a stomach-protecting medication. Early, uncontrolled clinical observations suggested that clearing these microclots could relieve long COVID symptoms.16Biochemical Journal. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications The emphasis on “uncontrolled” matters here. There has been no randomized trial of this approach. Giving three blood-thinning drugs simultaneously carries meaningful bleeding risk, and the entire framework remains in the hypothesis-testing phase. It is promising enough to warrant formal clinical trials, but not enough to justify self-treatment.
A Special Warning for Children
Aspirin should not be given to children with COVID-19 without specific medical direction, and this extends to multisystem inflammatory syndrome in children (MIS-C), a rare but serious post-COVID condition. While aspirin is sometimes used in MIS-C to manage coronary artery inflammation, at least one case report has documented Reye’s syndrome developing in a child treated with aspirin for MIS-C. The child developed hepatitis, seizures, and coma consistent with this rare but potentially fatal condition, which has long been associated with aspirin use in children during viral illness.17PubMed Central. Case Report: MIS-C Temporarily Associated With COVID-19 Complicated by Reye’s Syndrome When pediatric specialists do prescribe aspirin for MIS-C (typically for coronary aneurysms, similar to Kawasaki disease), they do so under close monitoring with awareness of this risk. Parents should never give aspirin to a child with a suspected or confirmed viral illness on their own initiative.
Where the Science Stands Now
The pandemic generated an enormous volume of research on aspirin and COVID-19, and sorting through it can leave anyone confused. The pattern is actually common in medicine: observational data suggests a benefit, a proper randomized trial fails to confirm it, and the field moves on. Heparin-based anticoagulation became the standard antithrombotic approach for hospitalized COVID-19 patients, and aspirin was set aside as a treatment for the virus. For people who take aspirin for cardiovascular reasons, the consensus is to continue it. For everyone else, starting aspirin specifically to treat or prevent COVID-19 is not supported by the best available evidence. The long COVID hypothesis remains the one area where aspirin might eventually find a defined role, but only if controlled trials confirm what uncontrolled observations have hinted at.