COVID-19 medicines span several drug classes, and their side effects range from an unpleasant metallic taste that lasts a few days to potentially serious drug interactions that require close medical supervision. The most widely prescribed outpatient treatment, Paxlovid, is best known for causing a bitter or metallic flavor in the mouth, while hospital-based therapies like remdesivir and dexamethasone carry their own organ-specific concerns. Because “COVID medicine” is not one drug but a whole pharmacy’s worth of them, the side-effect picture depends entirely on which treatment you are taking and what other medications are already in your system.
Paxlovid and Its Signature Metallic Taste
Paxlovid (nirmatrelvir combined with ritonavir) became the go-to oral antiviral for outpatient COVID-19, and its most talked-about side effect is dysgeusia, a distorted sense of taste that people commonly describe as metallic, bitter, or just plain foul. In a large pharmacovigilance study drawing on post-marketing adverse-event reports, dysgeusia showed up in about 17.5% of reports and was far more strongly associated with Paxlovid than with other antivirals.1PubMed. Postmarketing Reporting of Paxlovid-Related Dysgeusia: A Real-World Pharmacovigilance Study Women reported it more frequently than men. The taste disturbance typically starts within a day or two of beginning treatment and fades after the five-day course ends, but while it lasts, it can make eating and drinking genuinely unpleasant.
Beyond the taste issue, real-world safety surveillance using the FDA’s adverse-event reporting system flagged diarrhea and headache as common complaints, with relatively high signal intensity for both.2PLoS ONE. Data mining of adverse drug event signals with Nirmatrelvir/Ritonavir from FAERS That same analysis also identified signals for side effects not listed in the original prescribing information, including pale-colored stools, discolored urine, yellowish skin, and tongue coating. These are not yet confirmed as common reactions, but the reporting patterns were strong enough to warrant attention. If you notice unusual changes in your stool or skin color while taking Paxlovid, it is worth mentioning to your doctor.
Drug Interactions With Paxlovid
The ritonavir component in Paxlovid is not actually there to fight the virus. Its job is to slow down your liver’s processing of nirmatrelvir so the active drug stays in your bloodstream longer. It does this by powerfully blocking a liver enzyme called CYP3A4, and that creates a serious practical problem: the same enzyme processes dozens of other common medications.3PubMed Central. A Comprehensive Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Drug Interactions of Nirmatrelvir/Ritonavir When CYP3A4 is blocked, blood levels of those other drugs can spike to dangerous concentrations.
The list of potentially problematic interactions is long and includes certain blood thinners, cholesterol-lowering statins, heart-rhythm drugs, immunosuppressants used after organ transplants, and some psychiatric medications. For patients being treated for cancer, the interaction landscape is especially complex; a review of Paxlovid’s interactions with lung cancer therapies found that ritonavir-boosted nirmatrelvir is contraindicated with drugs that are highly dependent on CYP3A for clearance.4PubMed Central. Overview of Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Targeted Therapy and Supportive Care for Lung Cancer This is why prescribers need a full medication list before writing a Paxlovid prescription. In some cases, a conflicting drug can be temporarily paused; in others, Paxlovid simply cannot be used safely.
Paxlovid Rebound
Some people finish a five-day Paxlovid course, feel better for a day or two, and then see their symptoms return along with a positive test. This “Paxlovid rebound” became a widely discussed phenomenon. In the original clinical trial, viral rebound with recurring symptoms occurred in roughly 1 to 2% of treated patients. A retrospective study of more than 11,000 patients found the rate at about 3.5% within two to seven days after finishing treatment.5PubMed Central. An explanation for SARS-CoV-2 rebound after Paxlovid treatment Smaller studies in vaccinated individuals reported higher rates, though the sample sizes were small enough to make firm conclusions difficult.
Rebound is not technically a “side effect” of the drug in the traditional sense. It appears to reflect a situation where the virus was suppressed but not fully cleared during the five-day treatment window, allowing it to bounce back. A case series examining extended Paxlovid courses noted that some individuals experienced recurrence of previously improved symptoms after stopping the antiviral, raising questions about whether longer courses might help certain patients.6Communications Medicine. Impact of extended-course oral nirmatrelvir/ritonavir in established Long COVID: a case series For now, the standard course remains five days, and rebound episodes tend to be mild and self-limiting.
Molnupiravir and Mutagenicity Concerns
Molnupiravir (sold as Lagevrio) works differently from Paxlovid. It introduces errors into the virus’s genetic code during replication, eventually making the virus unable to function. The side effects during a standard five-day course tend to be mild and GI-related: diarrhea, nausea, and dizziness are the most commonly reported. But the bigger concern with molnupiravir is not what you feel during treatment; it is a theoretical worry about what the drug might do at a genetic level.
Because molnupiravir’s mechanism involves introducing mutations, researchers have raised questions about whether it could also cause mutations in human cells. The drug’s active component has shown the ability to cause mutations in host cells in laboratory settings, prompting calls for additional human genotoxicity data and long-term follow-up in treated patients, with particular concern about potential effects on reproduction.7PubMed. Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: The special case of molnupiravir This is one reason molnupiravir is contraindicated during pregnancy and was not authorized for children. It is also why Paxlovid, when available and appropriate, has generally been preferred by prescribers.
Remdesivir and Liver and Kidney Effects
Remdesivir (Veklury) is given intravenously, typically to hospitalized patients or occasionally as a short outpatient infusion. Its side-effect profile is dominated by concerns about two organs: the liver and the kidneys.
Mild elevations in liver enzymes have been documented repeatedly. A review of remdesivir’s hepatic effects noted that data from randomized controlled trials demonstrated a deleterious effect on the liver, and that while mild transaminase elevation is also a feature of COVID-19 itself, remdesivir-associated hepatotoxicity is a recognized concern.8PubMed Central. Hepatic manifestations of COVID-19 and effect of remdesivir on liver function in patients with COVID-19 illness A more recent study found that remdesivir was independently associated with mild increases in certain liver markers, particularly GGT and ALT, though the changes were modest.9Scientific Reports. The impact of remdesivir on renal and liver functions in severe COVID-19 patients with presence of viral load In practice, clinicians monitor liver function during treatment and will stop the drug if enzymes climb too high.
The kidney story is somewhat reassuring. Early in the pandemic there was concern because remdesivir’s formulation contains a carrier molecule that accumulates in people with poor kidney function. But studies have increasingly shown that kidney function does not worsen meaningfully with remdesivir treatment. In one study of 85 patients, the drug was stopped in just one patient due to a drop in kidney function, and that patient’s levels recovered after discontinuation.10PubMed Central. Liver and Renal Injury with Remdesivir Treatment in SARS-CoV-2 Patients A dedicated trial in people with severe kidney impairment, including those on dialysis, found no new safety signals and suggested that dose adjustments are not required.11Clinical Infectious Diseases. Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia: A Randomized Clinical Trial Other common side effects include nausea, and some patients develop rashes or experience a slowing of the heart rate during infusion.
Dexamethasone and Blood Sugar Spikes
Dexamethasone, a corticosteroid, was one of the earliest treatments shown to reduce deaths in severely ill COVID-19 patients who needed supplemental oxygen. Its side effects are well understood from decades of use in other conditions: the most relevant one for hospitalized COVID patients is a spike in blood sugar. Hyperglycemia is a common consequence of potent glucocorticoids, and it affects people both with and without pre-existing diabetes.12PubMed Central. Effectiveness of Dexamethasone for COVID-19 in Hospitalized Patients With Diabetes: A Retrospective Cohort Study For people who already have diabetes, managing blood sugar during a course of dexamethasone often requires temporary changes to insulin dosing or closer monitoring.
Other steroid side effects that can show up during a hospital stay include insomnia, mood changes, increased appetite, and fluid retention. Because dexamethasone suppresses the immune system (which is actually the point, in severe COVID), there is also an elevated risk of secondary infections like bacterial pneumonia or fungal infections, particularly with prolonged use. In the context of a short course for COVID, though, the life-saving benefit in severely ill patients clearly outweighs these risks.
Tocilizumab, Baricitinib, and Other Immune-Modulating Drugs
For patients whose immune response spirals into a dangerous inflammatory storm, doctors may add drugs that dampen specific parts of the immune system. Tocilizumab (an IL-6 receptor blocker) and baricitinib (a JAK inhibitor) are the two most commonly used. Both carry the expected cost of immune suppression: a higher rate of secondary infections.
A propensity-matched study comparing the two found that tocilizumab was associated with significantly more adverse effects than baricitinib. Secondary infections occurred in 32% of tocilizumab-treated patients versus 22% with baricitinib. Thrombotic events, meaning blood clots, occurred in 24% versus 16%. And acute liver injury was reported in 8% of the tocilizumab group compared with 3% in the baricitinib group.13PubMed Central. Outcomes and Adverse Effects of Baricitinib Versus Tocilizumab in the Management of Severe COVID-19 Mortality did not differ between the two, which means the choice often comes down to side-effect profile and drug availability. Both drugs increase susceptibility to infections and require monitoring of liver function and blood counts.
Monoclonal Antibodies
Monoclonal antibody treatments (like sotrovimab, bamlanivimab, and the casirivimab/imdevimab combination) were widely used in the earlier waves of the pandemic before evolving variants reduced their effectiveness. Their side-effect profile was generally mild. In one patient-reported outcomes study, about 76% of people who received a monoclonal antibody infusion reported no side effects at all. Among those who did, fever was most common at roughly 11%, followed by difficulty breathing at about 8%.14PubMed Central. The Treatment of COVID-19 With Monoclonal Antibody Therapy: Patient-Reported Outcomes
Infusion reactions, where the body responds to the IV delivery itself, were the most closely watched concern. A meta-analysis of four randomized trials involving about 3,000 participants found a slightly increased chance of infusion reactions with monoclonal antibodies compared to placebo, but the difference was not statistically significant.15PubMed Central. Adverse events associated with monoclonal antibodies used for treatment of COVID‐19: A systematic review and meta‐analysis In solid organ transplant recipients, who were a priority group for these treatments given their immune suppression, infusion-related adverse events were rare and generally mild.16PubMed Central. Monoclonal antibody treatment for COVID-19 in solid organ transplant recipients The main limitation of monoclonal antibodies today is not their safety but their effectiveness: most currently circulating variants have evolved enough that earlier antibody products no longer bind to the virus well enough to work.
Over-the-Counter Symptom Relief
Not every COVID medicine is a prescription antiviral. Many people manage mild COVID at home with the same over-the-counter remedies they would use for a cold or the flu: acetaminophen or ibuprofen for fever and body aches, decongestants for stuffiness, and cough suppressants. A review of these OTC treatments found that they are safe and effective for managing the same symptoms when caused by COVID-19.17PubMed Central. Treatment of COVID-19 symptoms with over the counter (OTC) medicines used for treatment of common cold and flu
The side effects here are the same ones you would encounter using these products for any other respiratory illness. Acetaminophen can stress the liver in high doses or when combined with alcohol. NSAIDs like ibuprofen can irritate the stomach or affect the kidneys with prolonged use. Decongestants containing pseudoephedrine can raise blood pressure. None of these are COVID-specific risks, but they are worth keeping in mind, especially if you are already taking a prescription COVID antiviral that has its own organ-related effects. Layering acetaminophen on top of remdesivir, for instance, means two drugs that can affect the liver, so your medical team should be aware of everything you are taking.
Hydroxychloroquine and Ivermectin
Early in the pandemic, hydroxychloroquine and ivermectin received enormous public attention as potential COVID treatments. Both went through clinical trials, and neither showed benefit for hospitalized patients with severe disease. A phase 2 randomized study comparing chloroquine, hydroxychloroquine, and ivermectin found that while all three had a favorable safety profile, none of them reduced the need for supplemental oxygen, ICU admission, ventilation, or death.18PubMed Central. Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection
Hydroxychloroquine’s known side effects include nausea, diarrhea, and, with prolonged use, potential heart rhythm disturbances (QT prolongation). Ivermectin at standard doses is generally well tolerated, but people who self-medicated with veterinary formulations during the pandemic risked overdose, which can cause neurological symptoms, vomiting, and liver damage. The safety question for both drugs is now somewhat academic: neither is recommended for COVID treatment by major health agencies, and spending time on their side effects matters less than understanding that they do not help.
Side Effects in Children and Pregnant People
Evidence on COVID treatments in children has lagged behind adult data, partly because severe pediatric disease is less common and partly because of the ethical complexity of drug trials in kids. A study of Paxlovid in children aged 6 and older with severe or critical COVID found that adverse events occurred in about 17% of both the treatment and control groups, with no serious events reported and no treatment discontinuations.19PubMed Central. Paxlovid for the treatment of severe or critical COVID-19 in children In other words, Paxlovid did not appear to add side-effect burden beyond what the illness itself was causing.
For pregnant and breastfeeding people, the data picture is thinner. A review of COVID therapeutics in pregnancy noted that while no serious safety signals had been raised for many agents, the data had serious limitations and important knowledge gaps remained about both safety and efficacy.20PubMed Central. A review of COVID-19 therapeutics in pregnancy and lactation Molnupiravir is explicitly not recommended during pregnancy due to its mutagenicity concerns. Remdesivir has been used in pregnant patients on a case-by-case basis, with monitoring. The general principle is that treatment decisions in pregnancy weigh the severity of the mother’s illness against the incomplete safety data, and that conversation should happen with a specialist.
When Side Effects Are Not Really Side Effects
One underappreciated factor in how people experience COVID treatment side effects is the nocebo effect, where expecting to feel bad actually makes you feel bad. This has been studied most rigorously in the context of COVID vaccines rather than therapeutics, but the principle applies broadly. A meta-analysis of vaccine trial placebo arms found that about 35% of people who received a dummy injection with no active ingredient still reported systemic symptoms like headache and fatigue after the first dose.21JAMA Network Open. Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials: A Systematic Review and Meta-analysis The analysis estimated that nocebo responses accounted for 76% of systemic side effects after the first vaccine dose.
Vaccine hesitancy itself predicted side-effect severity: people who were more anxious about getting vaccinated reported worse side effects after receiving the shot, and the effect was especially pronounced in men.22Scientific Reports. Vaccine hesitancy prospectively predicts nocebo side-effects following COVID-19 vaccination This does not mean that drug side effects are imaginary. Paxlovid’s metallic taste, for instance, is a direct pharmacological effect, not a psychological one. But it does mean that some portion of symptoms like headache, fatigue, and nausea that people attribute to their COVID medication may be influenced by anxiety, the underlying illness itself, or the simple act of paying close attention to how your body feels while you are sick and taking pills.
Telling Drug Side Effects Apart From Long COVID Symptoms
A related diagnostic puzzle involves distinguishing treatment side effects from the emergence of long COVID. Symptoms like fatigue, brain fog, and muscle aches can show up as part of post-acute COVID and can overlap with side effects of the medications used to treat the acute illness. A comprehensive review noted that differentiating between drug-related adverse events and long COVID relies on careful analysis of symptom timing, detailed symptom characterization, and sometimes advanced diagnostic tools.23PubMed. Differentiating COVID-19 vaccine-related adverse events from long COVID: A comprehensive review of clinical manifestations, pathophysiology, and diagnostic approaches
The most practical clue is timing. Drug side effects from a five-day course of Paxlovid or a three-day infusion of remdesivir should resolve within days of finishing treatment. If symptoms persist for weeks or months, they are more likely related to the virus itself than to the drug. Some patients who took extended Paxlovid courses for long COVID reported experiencing dizziness, shakiness, and tingling after stopping the medication, with those symptoms resolving about two weeks later.24PubMed Central. Impact of extended-course oral nirmatrelvir/ritonavir (Paxlovid) in established Long COVID: Case series and research considerations That kind of rebound or withdrawal pattern is distinct from the gradual, persistent symptom picture typical of long COVID, but it can be confusing in the moment. Keeping a simple symptom diary with start and stop dates for medications can help you and your doctor sort out what is causing what.