Do Hydroxychloroquine and Ivermectin Work?
Five years after Donald Trump declared a national COVID-19 emergency, here's what the research says.
This week marks five years since March 13, 2020, the day President Donald Trump declared a national state of emergency over the novel coronavirus outbreak. The White House issued The President's Coronavirus Guidelines for America three days later. Among other things, the guidelines advised Americans to avoid bars, restaurants, shopping trips, and social visits. They also said that governors in states with evidence of community transmission should close schools, bars, restaurants, food courts, gyms, and other indoor and outdoor venues.
Sticking to recent peer-reviewed science, and setting aside the political question of what the government should do with the information, what do we know now about the ways people tried to protect themselves from the virus? This week, we're looking at several measures—face masking, the vaccines—as well as the matter of how many Americans died of COVID-19 infections. Yesterday, we tackled face coverings. Today, let's probe what researchers have learned about the efficacy of hydroxychloroquine and ivermectin in treating COVID-19.
Six days after declaring a national emergency in 2020, Trump on March 19 hailed using the antimalaria compounds chloroquine and hydroxychloroquine as a potential "game changer" in the treatment of COVID-19. Trump's enthusiasm for the compounds was likely stoked, in part, by a guest earlier that week on Fox News claiming that hydroxychloroquine had a "100 percent cure rate against coronavirus." The guest was citing the unpublished results of a small nonrandomized study by a team led by French researcher Didier Raoult.
Feeling pressured by the president, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for chloroquine/hydroxychloroquine on March 28 for the treatment of COVID-19.
In early April 2020, a team of Australian researchers reported that the antiparasitic compound ivermectin killed COVID-19 viruses in infected cells in a petri dish. During the pandemic in the U.S. the use of hydroxychloroquine and ivermectin doubled and increased by tenfold, respectively, from January 30, 2020, to May 11, 2023, according to a 2025 Health Affairs analysis.
Citing emerging scientific data, the FDA on June 15, 2020, revoked its EUA after determining that chloroquine and hydroxychloroquine were unlikely to be effective in treating COVID-19. Again, the whiplash of confusing and contradictory claims and public health decisions about the efficacy of the compounds for treating COVID-19 ended up politicizing the issue.
Since 2020, there have been thousands of studies of the compounds. Google Scholar finds 32,800 and 15,800 citations of COVID-19 and hydroxychloroquine and ivermectin, respectively. Many initial studies came to contrary conclusions about their efficacy in treating COVID-19. So five years after the national emergency was declared, what have researchers determined?
Hydroxychloroquine
A September 2024 article in the journal Biomedicines reviewing the findings of clinical trials for ivermectin and chloroquine/hydroxychloroquine reported that "most phase III clinical trials" of the compounds "observed no treatment benefit in patients with COVID-19, underscoring the need for robust phase III clinical trials."
On the other hand, another study in PLOS Medicine published in September 2024 reporting the results of a randomized controlled trial found that "there was evidence of moderate protective benefit" for taking the drug to prevent COVID-19 infections. That study did, however, acknowledge that hydroxychloroquine "has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019."
The PLOS Medicine results mirrored that of an earlier meta-analysis of randomized controlled studies in the Journal of Thoracic Disease. The study by Chinese researchers found hydroxychloroquine reduced the risk of severe COVID-19 infections but "showed no effect on hospitalization or mortality." In a January 2024 study published in Social Determinants of Health, 871 healthy participants randomized to receive either hydroxychloroquine or a placebo were followed for 10 weeks. Over that period, 97 became infected with COVID-19, of whom 61 were taking a placebo. "Pre-exposure therapy with hydroxychloroquine appears to prevent moderate and severe illness caused by COVID-19 in asymptomatic persons," concluded the team of Iranian researchers.
A systematic review of the effectiveness of various pharmacological treatments for COVID-19 published in the February 27, 2025, issue of Frontiers in Pharmacology found that with respect to the efficacy of hydroxychloroquine in treating COVID-19, "there was no effect on mortality in 16 of 18 meta-analyses."
In a March 4, 2025, letter to Frontiers of Medicine, a Chinese research team after parsing retrospective clinical data for hospitalized COVID-19 patients reported that "low-dose [hydroxychloroquine] was associated with lower all-cause mortality." On the other hand, they observed, "No significant difference in all-cause mortality was found between the high-dose group and non-[hydroxychloroquine] group among the mild and critically ill patients."
Ivermectin
An August 2024 meta-analysis of 12 ivermectin randomized controlled trials of nonhospitalized patients in the International Journal of Antimicrobial Agents reported that "ivermectin did not reduce hospitalization, all-cause mortality or adverse events when compared with controls."
In April 2024, an ivermectin randomized controlled trial in the Journal of Infection concluded, "Ivermectin for COVID-19 is unlikely to provide clinically meaningful improvement in recovery, hospital admissions, or longer-term outcomes. Further trials of ivermectin for SARS-Cov-2 infection in vaccinated community populations appear unwarranted."
A July 2024 report in BMC Infectious Diseases of a randomized controlled trial in Sri Lanka using ivermectin to treat COVID-19 found, "Although ivermectin resulted in statistically significant lower viral load in patients with mild to moderate Covid-19, it had no significant effect on clinical symptoms." A March 2024 meta-analysis of 33 ivermectin randomized controlled trials by a team of Chinese researchers in the journal Heliyon found no significant difference in all-cause mortality rates or viral clearance rates between those treated with ivermectin and controls, although ivermectin did reduce the risk of mechanical ventilation for COVID-19 patients.
A February 2025 review study of ivermectin randomized controlled trials in Annals of Medicine & Surgery concluded that ivermectin showed no significant impact on critical outcomes such as mortality, mechanical ventilation, viral clearance rates, ICU admissions, or hospitalization rates compared to controls. Similarly, a February 2025 review article of randomized controlled trials by a team of Indian pharmaceutical researchers observed that "we consider Ivermectin ineffective in the management of COVID-19 disease, both as treatment and prophylaxis."
Nevertheless, ivermectin evangelists still argue that the medication is effective in treating COVID-19.
In December 2024, the French study that likely motivated Trump to tout hydroxychloroquine as a treatment for COVID-19 was retracted based on, among other things, "concerns raised by three of the authors themselves regarding the article's methodology and conclusion." However, other French researchers rejected that retraction as disinformation. It turns out that retractions are now politicized.
After five years of intensive research and debate, the initial hopes that these off-the-shelf compounds might offer significant benefits for the treatment of COVID-19 were not fulfilled. While some data suggest that taking hydroxychloroquine modestly lowers the risk of infection, most recent evidence concludes both compounds are largely ineffective as treatments for COVID-19 infections.
