COVID-19 drug repurposing research

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This article is about drugs that may be repurposed for treating COVID-19. For COVID-19 vaccines, see COVID-19 vaccine. For potential therapeutic drugs for COVID-19, see COVID-19 drug development.

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Drug repositioning (also known as drug repurposing, re-profiling, re-tasking, or therapeutic switching) is the repurposing of an approved drug for the treatment of a different disease or medical condition than that for which it was originally developed.[1] This is one line of scientific research which is being pursued to develop safe and effective COVID-19 treatments.[2][3][4] Other research directions include the development of a COVID-19 vaccine[5] and convalescent plasma transfusion.[6]

Several existing

Middle East respiratory syndrome (MERS), HIV/AIDS, and malaria, have been researched as potential COVID-19 treatments, with some moving into clinical trials.[7][8][9]

In a statement to the journal

genomic layout and the general replication kinetics and the biology of the MERS, SARS and [SARS-CoV-2] viruses are very similar, so testing drugs which target relatively generic parts of these coronaviruses is a logical step".[2]

Background

Outbreaks of novel emerging infections such as COVID-19 pose unique challenges to discover treatments appropriate for clinical use, given the small amount of time available for drug discovery.[10] Since the process of developing and licensing a new drug for COVID-19 was expected to pose a particularly long delay, researchers have been probing the existing compendium of approved antivirals and other drugs as a cost-effective strategy in the meantime.[3][10] In early 2020 hundreds of hospitals and universities began their own trials of existing safe drugs with repurposing potential against COVID-19.[11]

Drug repurposing usually requires three steps before taking the drug across the development pipeline: recognition of the right drug; systematic evaluation of the drug effect in clinical models; and estimation of usefulness in phase II clinical trials.[12]

One approach used in repositioning is to look for drugs that act through virus-related targets such as the RNA genome (i.e. remdesivir). Another approach concerns drugs acting through polypeptide packing (i.e. lopinavir).[10]

The rush to publish papers about the pandemic resulted in some scandals of inaccurate scientific publications.

false-positive results can be explained in terms of the base-rate fallacy and the rapid changes in clinical guidance regarding COVID-19 treatment could have been avoided if mechanistic evidence for and against repurposing candidates were carefully assessed[15] and the standard evidence amalgamation tools such as meta-analysis were routinely applied.[16]

Monoclonal antibodies

anti-IL-6 agents (tocilizumab)[17] and anti-IL-8 (BMS-986253).[18] (This is in parallel to novel monoclonal antibody drugs
developed specifically for COVID-19.)

granulocyte macrophage colony-stimulating factor receptor (GM-CSF-R).[19][20] It has been studied to see if it can improve the prognosis for patients with COVID-19 pneumonia and systemic hyperinflammation. One small study indicated some beneficial effects of treatment with mavrilimumab compared with those who were not.[21]

In January 2021, the UK National Health Service issued guidance that the immune modulating drugs tocilizumab and sarilumab were beneficial when given promptly to people with COVID-19 admitted to intensive care, following research which found a reduction in the risk of death by 24%.[22]

Tocilizumab

See also: Tocilizumab § COVID-19 Research
This section is an excerpt from Tocilizumab.[edit]


Hoffmann-La Roche.[23]

Tocilizumab was approved for medical use in the European Union in January 2009,[24] and in the United States in January 2010.[25][26]

Anticoagulants

Medications to prevent blood clotting have been suggested for treatment, and anticoagulant therapy with low-molecular-weight heparin appears to be associated with better outcomes in severe COVID‐19 showing signs of coagulopathy (elevated D-dimer).[27] Several anticoagulants have been tested in Italy, with low-molecular-weight heparin being widely used to treat patients, prompting the Italian Medicines Agency to publish guidelines on its use.[28][29]

Scientists have identified an ability of heparin to bind to the spike protein of the SARS-CoV-2 virus, neutralising it, and proposed the drug as a possible antiviral.[30]

A multicenter study on 300 patients researching the use of

therapeutic dosages was announced in Italy on 14 April.[31]

The anticoagulant dipyridamole is proposed as a treatment for COVID-19,[32] and a clinical trial is underway.[33]

Antidepressants

Many antidepressants have anti-inflammatory properties. An observational study in Paris area hospitals found that COVID-19 patients admitted to the hospital who were already taking an antidepressant had 44% less risk of intubation or death.[34][35] The potential mechanisms how fluvoxamine and fluoxetin are contributing to prevent the development of severe respiratory symptoms of COVID-19 by protecting the type 2 lung alveolar cells have been summarized in a review in March 2022.[36]

Fluvoxamine

Further information: Fluvoxamine § COVID-19 Research

In October 2021, the TOGETHER trial, a large clinical trial in Brazil, reported that treating high-risk

outpatients with an early diagnosis of COVID-19 with 100 mg fluvoxamine twice daily for 10 days reduced by up to about 65% the risk of hospitalization. The effect was reduced to about 32% with low adherence, possibly due to intolerance. There was also a reduction in the number of deaths by up to about 90% with high adherence. The drug was studied because of its anti-inflammatory effects, but the mechanism of action against COVID-19 remains uncertain.[37][38][39]

On 16 December, the NIH found that use of fluvoxamine did not impact incidence of covid-related hospitalizations and considered the evidence insufficient to recommend either for or against the drug.[40]

On 23 December, under very low certainty evidence, the Ontario clinical practice guideline suggested considering the drug to treat mildly ill patients within 7 days of symptom onset.[41]

In May 2022, based on a review of available scientific evidence, the US Food and Drug Administration (FDA) declined a request to issue an Emergency Use Authorization (EUA) for fluvoxamine to treat COVID-19, saying that the data were not sufficient to conclude that it may be effective in treating non-hospitalized people with COVID-19 to prevent serious illness or hospitalization. University of Minnesota professor David Boulware, who filed the EUA application, said that the standard that they were holding for fluvoxamine was a different standard than the other big pharma trials, with Paxlovid and molnupiravir and the monoclonals.[42][43]

Antioxidants

Acetylcysteine (NAC)

Acetylcysteine is being considered as a possible treatment for COVID-19.[44]

Antiparasitics

The idea of repurposing host-directed drugs for antiviral therapy has experienced a renaissance.[45] In some cases the research has highlighted fundamental limitations to their use for the treatment of acute RNA virus infections.[46] Antiparasitics that have been investigated include chloroquine,[47] hydroxychloroquine,[48] mefloquine,[49][50] ivermectin,[51] and atovaquone.[52]

Chloroquine and hydroxychloroquine

This section is an excerpt from Chloroquine and hydroxychloroquine during the COVID-19 pandemic.[edit]


A World Health Organization infographic that states that hydroxychloroquine does not prevent illness or death from COVID-19.

COVID-19.[54] Neither drug has been useful to prevent or treat SARS-CoV-2 infection.[55][56][57][58][59][60] Administration of chloroquine or hydroxychloroquine to COVID-19 patients has been associated with increased mortality and adverse effects, such as QT prolongation.[61][62] Researchers estimate that off-label use of hydroxychloroquine in hospitals during the first phase of the pandemic caused 17,000 deaths worldwide.[63] The widespread administration of chloroquine or hydroxychloroquine, either as monotherapies or in conjunction with azithromycin, has been associated with deleterious outcomes, including QT interval prolongation. As of 2024, scientific evidence does not substantiate the efficacy of hydroxychloroquine, with or without the addition of azithromycin, in the therapeutic management of COVID-19.[61]

Cleavage of the SARS-CoV-2 S2 spike protein required for viral entry into cells can be accomplished by proteases TMPRSS2 located on the cell membrane, or by cathepsins (primarily cathepsin L) in endolysosomes.[64] Hydroxychloroquine inhibits the action of cathepsin L in endolysosomes, but because cathepsin L cleavage is minor compared to TMPRSS2 cleavage, hydroxychloroquine does little to inhibit SARS-CoV-2 infection.[64]

Several countries initially used chloroquine or hydroxychloroquine for treatment of persons hospitalized with COVID-19 (as of March 2020), though the drug was not formally approved through clinical trials.

off label for potential treatment of the disease.[68] On 24 April 2020, citing the risk of "serious heart rhythm problems", the FDA posted a caution against using the drug for COVID-19 "outside of the hospital setting or a clinical trial".[69]

Their use was withdrawn as a possible treatment for COVID-19 infection when it proved to have no benefit for hospitalized patients with severe COVID-19 illness in the international Solidarity trial and UK RECOVERY Trial.[70][71] On 15 June 2020, the FDA revoked its emergency use authorization, stating that it was "no longer reasonable to believe" that the drug was effective against COVID-19 or that its benefits outweighed "known and potential risks".[72][73][74] In fall of 2020, the National Institutes of Health issued treatment guidelines recommending against the use of hydroxychloroquine for COVID-19 except as part of a clinical trial.[53]

In 2021, hydroxychloroquine was part of the recommended treatment for mild cases in India.[75]

In 2020, the speculative use of hydroxychloroquine for COVID-19 threatened its availability for people with established indications (malaria and auto-immune diseases).[57]

Ivermectin

This section is an excerpt from Ivermectin during the COVID-19 pandemic.[edit]
Ball-and-stick model of Ivermectin

Ivermectin is an antiparasitic drug that is well established for use in animals and people.[76] The World Health Organization (WHO),[77] the European Medicines Agency (EMA),[78] the United States Food and Drug Administration (FDA),[79] and the Infectious Diseases Society of America (IDSA)[80] all advise against using ivermectin in an attempt to treat or prevent COVID-19.

Early in the COVID-19 pandemic, laboratory research suggested ivermectin might have a role in preventing or treating COVID-19.[81] Online misinformation campaigns and advocacy boosted the drug's profile among the public. While scientists and physicians largely remained skeptical, some nations adopted ivermectin as part of their pandemic-control efforts. Some people, desperate to use ivermectin without a prescription, took veterinary preparations, which led to shortages of supplies of ivermectin for animal treatment. The FDA responded to this situation by saying "You are not a horse" in a Tweet to draw attention to the issue, which they were later sued for.[82][83]

Subsequent research failed to confirm the utility of ivermectin for COVID-19,[84][85] and in 2021 it emerged that many of the studies demonstrating benefit were faulty, misleading, or fraudulent.[86][87] Nevertheless, misinformation about ivermectin continued to be propagated on social media and the drug remained a cause célèbre for anti-vaccinationists and conspiracy theorists.[88]

Antivirals

Research is focused on repurposing approved antiviral drugs that have been previously developed against other viruses, such as

triazavirin,[92] and umifenovir.[93]

The combination of

Hela cells. Artesunate/pyronaridine showed a virus titer inhibition rate of 99% or more after 24 hours, while cytotoxicity was also reduced.[94] A preprint published in July 2020, reported that pyronaridine and artesunate exhibit antiviral activity against SARS-CoV-2 and influenza viruses using human lung epithelial (Calu-3) cells.[95] It is in phase II clinical trial in South Korea[96][97][98] and in South Africa.[99]

Molnupiravir is a drug developed to treat influenza. It is in Phase III trials as a treatment for COVID-19.[100][101][102][103][104] In December 2020, scientists reported that the antiviral drug molnupiravir developed for the treatment of influenza can completely suppress SARS-CoV-2 transmission within 24 hours in ferrets whose COVID-19 transmission they find to closely resemble SARS-CoV-2 spread in human young-adult populations.[105][106] A clinical trial, which has not as of 1 October 2021 been peer reviewed, suggests molnupiravir taken orally can reduce the risk of hospitalization and prevent death in patients diagnosed with COVID-19. The drug needs to be given early to be effective.[107][108] As of 1 January 2022, Molnupiravir has been approved for emergency use against COVID-19 in the United Kingdom, India, and the United States.[109]

Niclosamide was identified as a candidate antiviral in an in vitro drug screening assay done in South Korea.[110]

Protease inhibitors, which specifically target the protease 3CLpro, are being researched and developed in the laboratory such as CLpro-1, GC376, and Rupintrivir.[111][112][113]

Coronaviruses species possess an intrinsic resistance to ribavirin.[114]

Sofosbuvir/daclatasvir is a drug combination developed to treat hepatitis C. In October 2020, a meta-analysis found a significantly lower risk of all-cause mortality with the drug combination when given to hospitalized patients.[115]

Favipiravir

Favipiravir is an antiviral drug approved for the treatment of influenza in Japan.[116][89] There is limited evidence suggesting that, compared to other antiviral drugs, favipiravir might improve outcomes for people with COVID-19, but more rigorous studies are needed before any conclusions can be drawn.[117]

Chinese clinical trials in Wuhan and Shenzhen claimed to show that favipiravir was "clearly effective".[118] Of 35 patients in Shenzhen tested negative in a median of 4 days, while the length of illness was 11 days in the 45 patients who did not receive it.[119] In a study conducted in Wuhan on 240 patients with pneumonia half were given favipiravir and half received umifenovir. The researchers found that patients recovered from coughs and fevers faster when treated with favipiravir, but that there was no change in how many patients in each group progressed to more advanced stages of illness that required treatment with a ventilator.[120]

On 22 March 2020, Italy approved the drug for experimental use against COVID-19 and began conducting trials in the three regions most affected by the disease.[121] The Italian Pharmaceutical Agency reminded the public that the existing evidence in support of the drug is scant and preliminary.[122]

On 30 May 2020, the Russian Health Ministry approved a generic version of favipiravir named Avifavir, which proved highly effective in the first phase of clinical trials.[123][124][125]

In June 2020, India approved the use of a generic version of favipravir called FabiFlu, developed by Glenmark Pharmaceuticals, in the treatment of mild to moderate cases of COVID-19.[126]

On 26 May 2021, a systematic review found a 24% greater chance of clinical improvement when administered in the first seven days of hospitalization, but no statistically significant reduction in mortality for any of the groups, including hospitalized patients and those with mild or moderate symptoms.[127][128]

Lopinavir/ritonavir

polyprotein
.

In March 2020, the main protease (3CLpro) of the SARS-CoV-2 virus was identified as a target for post-infection drugs. The enzyme is essential for processing the replication-related polyprotein. To find the enzyme, scientists used the genome published by Chinese researchers in January 2020 to isolate the main protease.[129] Protease inhibitors approved for treating human immunodeficiency viruses (HIV) – lopinavir and ritonavir – have preliminary evidence of activity against the coronaviruses, SARS and MERS.[7][130] As a potential combination therapy, they are used together in two Phase III arms of the 2020 global Solidarity project on COVID-19.[130][131] A preliminary study in China of combined lopinavir and ritonavir found no effect in people hospitalized for COVID-19.[132]

One study of lopinavir/ritonavir (Kaletra), a combination of the antivirals lopinavir and ritonavir, concluded that "no benefit was observed".[132][133] The drugs were designed to inhibit HIV from replicating by binding to the protease. A team of researchers at the University of Colorado are trying to modify the drugs to find a compound that will bind with the protease of SARS-CoV-2.[134] There are criticisms within the scientific community about directing resources to repurposing drugs specifically developed for HIV/AIDS because such drugs are unlikely to be effective against a virus lacking the specific HIV-1 protease they target.[2] The WHO included lopinavir/ritonavir in the international Solidarity trial.[135]

On 29 June, the chief investigators of the UK RECOVERY Trial reported that there was no clinical benefit from use of lopinavir-ritonavir in 1,596 people hospitalized with severe COVID-19 infection over 28 days of treatment.[136][137]

A study published in October 2020, screening those drugs approved by the US Food and Drug Administration (FDA) which target SARS-CoV-2 spike (S) protein proposed that the current unbalanced combination formula of lopinavir might in fact interfere with the ritonavir's blocking activity on the receptor binding domain-human angiotensin converting enzyme-2 (RBD-hACE2) interaction, thus effectively limiting its therapeutic benefit in COVID-19 cases.[138]

In 2022, the

PANORAMIC trial is testing the effectiveness of nirmatrelvir combined with ritonavir, and molnupiravir in preventing hospitalization and helping faster recovery for people aged over 50 and those at higher risk due to underlying health conditions.[139][140] As of March 2022 has over 16,000 people enrolled as participants making it the largest study into COVID-19 antivirals.[141]

Remdesivir

See also: Remdesivir § COVID-19
This section is an excerpt from Remdesivir.[edit]


COVID‑19 in numerous countries.[147]

Remdesivir was originally developed to treat hepatitis C,[148] and was subsequently investigated for Ebola virus disease and Marburg virus infections[149] before being studied as a post-infection treatment for COVID‑19.[150]

Remdesivir is a

nucleotide analogue inhibitor of viral RNA polymerase.[151]

The most common side effect in healthy volunteers is raised blood levels of

liver enzymes.[142] The most common side effect in people with COVID‑19 is nausea.[142] Side effects may include liver inflammation and an infusion-related reaction with nausea, low blood pressure, and sweating.[152]

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[153]

Immunomodulatory treatments

Baricitinib

See also: Baricitinib § COVID-19 research

In May 2022, the US Food and Drug Administration (FDA) approved barictinib for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).[154][155] Barictinib is the first immunomodulatory treatment for COVID-19 to receive FDA approval.[155]

In the United States, barictinib is authorized under an

emergency use authorization (EUA) for the treatment of COVID-19 in hospitalized people aged 2 to less than 18 years of age who require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation.[154]

Immunosuppressants

Anakinra

Further information: Anakinra § COVID-19 research

In December 2021, anakinra (Kineret) was authorized in the European Union for the treatment of COVID-19 in adults with pneumonia requiring supplemental oxygen (low or high flow oxygen) and who are at risk of developing severe respiratory failure, as determined by blood levels of a protein called suPAR (soluble urokinase plasminogen activator receptor) of at least 6 ng per ml."[156][157]

Interferons

Drugs with immune modulating effects that may prove useful in COVID-19 treatment include type I Interferons such as Interferon-β, peginterferon alpha-2a and -2b.[158][159]

COPD.[135]

Steroids

Systemic corticosteroids have a small but statistically significant beneficial effect in reducing 30-day all-cause mortality in individuals hospitalized with COVID-19.[161]

Budesonide

Administration of this inhaled steroid early in the course of COVID-19 infection has been found to reduce the likelihood of needing urgent medical care and reduced the time to recovery.[162][163] More studies are on-going.[163] In April 2021, budesonide was approved by authorities in the UK for off-label use to treat COVID-19 on a case-by-case basis.[164]

Ciclesonide

Ciclesonide, an inhaled corticosteroid for asthma, was identified as a candidate antiviral in an in vitro drug screening assay done in South Korea.[110] It has been used for treatment of pre-symptomatic COVID-19 patients and is under-going clinical trials.[165]

Dexamethasone

See also: Dexamethasone § COVID-19, and RECOVERY Trial § Dexamethasone
A vial of dexamethasone for injection

chronic obstructive lung disease among others.[166] A multi-center, randomized controlled trial of dexamethasone in treating acute respiratory distress syndrome (ARDS), published in February 2020, showed reduced need for mechanical ventilation and mortality.[167] Dexamethasone is only helpful in people requiring supplemental oxygen. Following an analysis of seven randomized trials,[168] the WHO recommends the use of systemic corticosteroids in guidelines for treatment of people with severe or critical illness, and that they not be used in people that do not meet the criteria for severe illness.[169]

On 16 June, the

Oxford University RECOVERY Trial issued a press release announcing preliminary results that the drug could reduce deaths by about a third in participants on ventilators and by about a fifth in participants on oxygen; it did not benefit patients who did not require respiratory support. The researchers estimated that treating 8 patients on ventilators with dexamethasone saved one life, and treating 25 patients on oxygen saved one life.[170] Several experts called for the full dataset to be published quickly to allow wider analysis of the results.[171][172] A preprint was published on 22 June[173] and the peer-reviewed article appeared on 17 July.[174]

Based on those preliminary results, dexamethasone treatment has been recommended by the US National Institutes of Health (NIH) for patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen but are not mechanically ventilated. The NIH recommends against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen.[175] In July 2020, the World Health Organization (WHO) stated they are in the process of updating treatment guidelines to include dexamethasone or other steroids.[176]

The Infectious Diseases Society of America (IDSA) guideline panel suggests the use of glucocorticoids for patients with severe COVID-19; where severe is defined as patients with oxygen saturation (SpO2) ≤94% on room air, and those who require supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).[177] The IDSA recommends against the use of glucocorticoids for those with COVID-19 without hypoxemia requiring supplemental oxygen.[177]

In July 2020, the European Medicines Agency (EMA) started reviewing results from the RECOVERY study arm that involved the use of dexamethasone in the treatment of patients with COVID-19 admitted to the hospital to provide an opinion on the results. It focused particularly on the potential use of the drug for the treatment of adults with COVID-19.[178]

In September 2020, the WHO released updated guidance on using corticosteroids for COVID-19.[179][180] The WHO recommends systemic corticosteroids rather than no systemic corticosteroids for the treatment of people with severe and critical COVID-19 (strong recommendation, based on moderate certainty evidence).[179] The WHO suggests not to use corticosteroids in the treatment of people with non-severe COVID-19 (conditional recommendation, based on low certainty evidence).[179]

In September 2020, the European Medicines Agency (EMA) endorsed the use of dexamethasone in adults and adolescents (from twelve years of age and weighing at least 40 kilograms (88 lb)) who require supplemental oxygen therapy.[181] Dexamethasone can be taken by mouth or given as an injection or infusion (drip) into a vein.[181]

Hydrocortisone

In September 2020, a meta-analysis published by the

WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group found hydrocortisone to be effective in reducing mortality rate of critically ill COVID-19 patients when compared to other usual care or a placebo.[182]

The use of corticosteroids can cause a severe and deadly "hyperinfection" syndrome for people with strongyloidiasis, which may be an underlying condition in populations exposed to the parasite Strongyloides stercoralis. This risk can be mitigated by the presumptive use of ivermectin before steroid treatment.[183]

Methylprednisolone

In March–April 2020, a small bioinformatics company, AdvaitaBio, used its data analysis platform, iPathwayGuide, to analyze one of the first

transcriptomics data sets that became available from COVID-19 patients.[184] This analysis was able to identify methylprednisolone as a drug that could potentially help patients with severe cases of this disease. The analysis of the molecular data indicated that patients with severe COVID-19 suffered from the cytokine storm syndrome, and also identified the specific pathways and mechanisms through which methylprednisolone would help revert many of the important gene expression changes induced by the cytokine storm.[185] A subsequent clinical trial undertaken in the Henry Ford Health Systems showed that methylprednisolone reduced mortality by approximately 44% (from 29.6% to 16.6%).[186] The results contradicted flagrantly the recommendations of the World Health Organization, which at the time, had a standing recommendation NOT to use systemic steroids in COVID-19 patients.[187] This, together with the very tense scientific environment cause by theretraction of some early COVID-19-related papers,[188] delayed the publication of these results by several months. This was very unfortunate, since methylprednisolone is low-cost and widely available and could have prevented many thousands of deaths. Several months later, the results of the RECOVERY trial (see dexamethasone above) also showed steroids as being effective in reducing mortality, and helped change the general opinion about steroid treatments in COVID-19. The drug repurposing analysis that was first to propose a steroid for severe COVID-19 case was eventually published in the journal Bioinformatics[185]
Currently, steroids including methylprednisolone and dexamethasone are part of the standard of care in severe cases of COVID-19.

For a composite end point of preventing ICU admission, need for mechanical ventilator or mortality, the number needed to treat (NNT) to benefit a single patient was only 5 for methylprednisolone when used early in hospitalization. The NNT necessary for methylprednisolone to avoid a death was only 8 for all hospitalized patients.[186][187] This is in contrast to the RECOVERY trial (NCT04323592) for dexamethasone (see Dexamethasone above), where NNT was 8 for patients on mechanical ventilation, and 25 for patients needed oxygen to prevent mortality.

Vitamins

Vitamin C

Further information: Vitamin C § COVID-19
See also: COVID-19 misinformation § Vitamin C

Supplementation with vitamin C, has been suggested as part of the supportive management of COVID-19, as serum levels of the vitamin are depleted in the acute stage of infection owing to increased metabolic demands.[189] In April 2021, the US National Institutes of Health (NIH) COVID-19 Treatment Guidelines stated that "there are insufficient data to recommend either for or against the use of vitamin C for the prevention or treatment of COVID-19."[190] In an update posted December 2022, the NIH position was unchanged:

  • There is insufficient evidence for the COVID-19 Treatment Guidelines Panel (the Panel) to recommend either for or against the use of vitamin C for the treatment of COVID-19 in nonhospitalized patients.
  • There is insufficient evidence for the Panel to recommend either for or against the use of vitamin C for the treatment of COVID-19 in hospitalized patients.[191]

Three meta-analyses of people hospitalized with severe COVID-19 - with a high overlap in the clinical trials being included - reported a significant reduction in the risk of all-cause, in-hospital mortality with the administration of vitamin C relative to no vitamin C. There were no significant differences in ventilation incidence, hospitalization duration or length of intensive care unit stay between the two groups. The majority of the trials used intravenous administration of the vitamin.[192][193][194] Acute kidney injury was lower in people treated with vitamin C treatment. There were no differences in the frequency of other adverse events due to the vitamin.[194] All three journal articles concluded that further large-scale studies are needed to affirm its mortality benefits before issuing updated guidelines and recommendations.[192][193][194]

Vitamin D

Further information: Vitamin D § COVID-19
See also: COVID-19 misinformation § Vitamin D
Oral vitamin D tablets

During the COVID-19 pandemic, there has been interest in vitamin D status and supplements, given the significant overlap in the risk factors for severe COVID-19 and vitamin D deficiency.[195] These include obesity, older age, and Black or Asian ethnic origin, and it is notable that vitamin D deficiency is particularly common within these groups.[195]

The National Institutes of Health (NIH) COVID-19 Treatment Guidelines states "there is insufficient evidence to recommend either for or against the use of vitamin D for the prevention or treatment of COVID-19."[196]

The general recommendation to consider taking vitamin D supplements, particularly given the levels of vitamin D deficiency in Western populations, has been repeated.[197] As of February 2021, the English National Institute for Health and Care Excellence (NICE) continued to recommend small doses of supplementary vitamin D for people with little exposure to sunshine, but recommended that practitioners should not offer a vitamin D supplement solely to prevent or treat COVID-19, except as part of a clinical trial.[197]

Multiple studies have reported links between pre-existing vitamin D deficiency and the severity of the disease. Several systematic reviews and meta-analyses of these show that vitamin D deficiency may be associated with a higher probability of becoming infected with COVID-19, and have clearly demonstrated there are significant associations between deficiency and a greater severity of the disease, including relative increases in hospitalization and mortality rates of about 80%.[198][199][200] The quality of some of the studies included and whether this demonstrates a causal relationship has been questioned.[201]

Many clinical trials are underway or have been completed assessing the use of oral vitamin D and its metabolites such as calcifediol for prevention or treatment of COVID-19 infection, especially in people with vitamin D deficiency.[202][203][195][204]

The effects of oral vitamin D supplementation on the need for intensive care unit (ICU) admission and mortality in hospitalized COVID-19 patients has been the subject of a meta-analysis.[205] A much lower ICU admission rate was found in patients who received vitamin D supplementation, which was only 36% of that seen in patients without supplementation (p<0.0001).[205] No significant effects on mortality were found in this meta-analysis.[205] The certainty of these analyses is limited by the heterogenicity in the studies which include both vitamin D3 (cholecalciferol) and calcifediol, but these findings indicate a potential role in improving COVID-19 severity, with more robust data being required to substantiate any effects on mortality.[205][206]

Calcifediol, which is

25-hydroxyvitamin D, is more quickly activated,[207] and has been used in several trials.[203] Review of the published results suggests that calcifediol supplementation may have a protective effect on the risk of ICU admissions in COVID-19 patients.[201]

Minerals

Zinc

The National Institutes of Health (NIH) COVID-19 Treatment Guidelines states "there is insufficient evidence to recommend either for or against the use of zinc for the treatment of COVID-19" and that "the Panel recommends against using zinc supplementation above the recommended dietary allowance for the prevention of COVID-19, except in a clinical trial (BIII)."[208]

Others

  • Antibiotics: Some antibiotics that have been identified as potentially repurposable as COVID-19 treatments,[209][210] including:
  • antirheumatic agent bucillamine in patients with mild-moderate COVID-19.[218]
  • Colchicine: Researchers from the Montreal Heart Institute in Canada are studying the role of colchicine in reducing inflammation and pulmonary complications in patients with mild symptoms of COVID-19.[219] The study, named COLCORONA, was recruiting 6000 adults 40 and older who were diagnosed with COVID-19 and experienced mild symptoms not requiring hospitalization.[219][220] Women who were pregnant or breastfeeding or who did not have an effective contraceptive method were not eligible. The trial results are favorable, but inconclusive.[220]
  • Fenofibrate and bezafibrate have been suggested for treatment of life-threatening symptoms of COVID-19.[32][221] Fenofibrate also lowered severe progressive inflammation markers in hospitalized COVID-19 patients within 48 hours of treatment in an Israeli study.[222] It showed extremely promising results by interfering with how coronavirus reproduce.[223]
  • nanoFenretinide is nanoparticle sized fenretinide and repurposed oncology drug approved to enter the clinic for a lymphoma indication.[224] It was identified as a candidate antiviral in an in vitro drug screening assay done in South Korea.[110] Fenretinide's clinical safety profile also makes it an ideal candidate in combination regimens.[citation needed]
  • H2 receptor antagonists
    are under investigation.
  • Ibuprofen: A trial called "Liberate" has been started in the United Kingdom to determine the effectiveness of ibuprofen in reducing the severity and progression of lung injury which results in breathing difficulties for COVID-19 patients. Subjects are to receive three doses of a special formulation of the drug – lipid ibuprofen – in addition to usual care.[226][227]
  • Influenza vaccine: A clinical cohort study in Brazil found that COVID-19 patients who received a recent influenza vaccine needed less intensive care support, less invasive respiratory support, and were less likely to die.[228]
  • Sildenafil, more commonly known by the brand name Viagra, is proposed as a treatment for COVID-19,[32] and a Phase III clinical trial is underway.[229]

Found ineffective

The use of

etesevimab and bamlanivimab together was found ineffective against the Omicron variant.[232]

References

  1. ^ "Repurposing Drugs". National Center for Advancing Translational Sciences (NCATS). U.S. Department of Health & Human Services, National Institutes of Health. 7 November 2017. Archived from the original on 4 October 2020. Retrieved 26 March 2020.
  2. ^
    S2CID 213394680
    .
  3. ^
    PMID 36233149
    .
  4. S2CID 25267555
    .
  5. ^ "COVID-19 Vaccine Frontrunners". Archived from the original on 6 May 2020. Retrieved 16 April 2020.
  6. PMID 32253318
    .
  7. ^
    PMID 32127666
    .
  8. ^ "COVID-19 treatment and vaccines tracker (Choose tab of interest, apply filters to view select data)". Milken Institute. 2 June 2020. Archived from the original on 3 June 2020. Retrieved 3 June 2020.
  9. PMID 32282022
    .
  10. ^
    PMID 32889701
    .
  11. ^ Zimmer C (30 January 2021). "How the Search for Covid-19 Treatments Faltered While Vaccines Sped Ahead". The New York Times. Archived from the original on 15 November 2021. Retrieved 15 November 2021.
  12. S2CID 218556384
    .
  13. PMID 33422679
    .
  14. S2CID 244863256
    .
  15. PMID 36258007
    .
  16. S2CID 232217402
    .
  17. ^ "RECOVERY Trial". Archived from the original on 12 October 2020. Retrieved 17 June 2020.
  18. ^ "Anti-Interleukin-8 (Anti-IL-8) for Patients With COVID-19". ClinicalTrials.gov. Archived from the original on 12 June 2022. Retrieved 10 September 2020.
  19. ^ "Statement On A Nonproprietary Name Adopted By The USAN Council: Mavrilimumab" (PDF). American Medical Association. Archived from the original (PDF) on 28 September 2012.
  20. PMID 21613310
    .
  21. PMID 32835256
    .
  22. ^ "Arthritis drugs effective in improving survival in sickest COVID-19 patients". National Institute for Health Research. 7 January 2021. Archived from the original on 25 January 2021. Retrieved 21 February 2021.
  23. ^ Markus Harwart (2008). "Die Entwicklung von Tocilizumab" [The development of tocilizumab] (in German). Krankenpflege-Journal. Archived from the original on 15 October 2018. Retrieved 30 April 2016.
  24. ^ "RoActemra EPAR". European Medicines Agency. 17 September 2018. Archived from the original on 18 December 2021. Retrieved 18 December 2021.
  25. ^ "Drug Approval Package: Actemra (Tocilizumab) Injection BLA 125276". U.S. Food and Drug Administration (FDA). 9 March 2010. Archived from the original on 26 January 2022. Retrieved 1 October 2023.
  26. ^ "Drug Approval Package: Actemra (tocilizumab) Solution for Subcutaneous Injection NDA #125472". accessdata.fda.gov. 17 July 2014. Archived from the original on 23 January 2023. Retrieved 1 October 2023.
  27. PMID 32220112
    .
  28. ^ "Medicines usable for treatment of COVID-19 disease". Italian Medicines Agency. Archived from the original on 15 April 2021. Retrieved 29 March 2021.
  29. ^ "Low molecular weight heparins in the treatment of adult patients with COVID-19". AIFA Italian Medicines Agencty. 24 November 2020. Archived from the original on 27 August 2021. Retrieved 30 March 2021.
  30. ^ Weintraub A (20 July 2020). "How COVID-19 could be crippled by an age-old blood thinner". Fierce Biotech. Archived from the original on 22 July 2020. Retrieved 22 July 2020.
  31. ^ "Coronavirus, al via studio su eparina per 300 pazienti". Adnkronos. Archived from the original on 6 October 2020. Retrieved 15 April 2020.
  32. ^
    PMID 32374264
    .
  33. ^ "Chinese Clinical Trial Register (ChiCTR) – The world health organization international clinical trials registered organization registered platform". www.chictr.org.cn. Archived from the original on 6 October 2020. Retrieved 30 April 2020.
  34. ^ Landhuis E (12 November 2021). "Investigating Antidepressants' Surprising Effect on COVID Deaths". Scientific American. Archived from the original on 1 December 2021. Retrieved 1 December 2021.
  35. S2CID 231794088
    .
  36. PMID 35409171
    .
  37. S2CID 240229837
    .
  38. ^ Fox M (28 October 2021). "Cheap, generic anti-depressant may reduce severe Covid-19 disease, study finds". CNN. Archived from the original on 22 November 2021. Retrieved 22 November 2021.
  39. PMID 34717820
    .
  40. ^ "Fluvoxamine Clinical Data". COVID-19 Treatment Guidelines. 16 December 2022. Archived from the original on 26 January 2022. Retrieved 7 February 2022.
  41. S2CID 245441405. Archived from the original on 24 December 2021. Retrieved 24 December 2021.{{cite journal}}: CS1 maint: numeric names: authors list (link
    )
  42. ^ "FDA declines to authorize common antidepressant as COVID treatment". Reuters. 16 May 2022. Archived from the original on 17 May 2022. Retrieved 18 May 2022.
  43. ^ Memorandum Explaining Basis for Declining Request for Emergency Use Authorization of Fluvoxamine Maleate (PDF) (Memorandum). Food and Drug Administration. 16 May 2022. 4975580. Archived (PDF) from the original on 17 May 2022. Public Domain This article incorporates text from this source, which is in the public domain.
  44. ^ "N-Acetylcysteine as Adjuvant Therapy for COVID-19 – A Perspective on the Current State of the Evidence". Archived from the original on 20 February 2022. Retrieved 20 February 2022.
  45. PMID 27036359
    .
  46. PMID 34218010
    .
  47. PMID 32020029
    .
  48. PMID 32205204
    .
  49. PMID 32817221
    .
  50. Federal Biomedical Agency. 10 April 2020. Archived from the original
    on 11 April 2020. Retrieved 11 April 2020.
  51. PMID 32251768
    .
  52. ^ "Atovaquone and Azithromycin Combination for Confirmed COVID-19 Infection". ClinicalTrials.gov. Archived from the original on 24 November 2020. Retrieved 10 September 2020.
  53. ^ a b "Chloroquine or Hydroxychloroquine". COVID-19 Treatment Guidelines. National Institutes of Health. Archived from the original on 28 August 2020. Retrieved 14 February 2021.
  54. ^ "Coronavirus (COVID-19) Update: Daily Roundup March 30, 2020". FDA. 30 March 2020. Archived from the original on 19 October 2020. Retrieved 28 February 2021.
  55. PMID 33476807
    .
  56. PMID 32350928
    .
  57. ^
    PMID 32269021
    .
  58. ^ "Assessment of Evidence for COVID-19-Related Treatments: Updated 4/3/2020". American Society of Health-System Pharmacists. Archived from the original on 14 April 2021. Retrieved 7 April 2020.
  59. PMID 32232419
    .
  60. PMID 33624299
    .
  61. ^
    PMID 38425958
    .
  62. PMID 32438018
    .
  63. S2CID 266754199
    .
  64. ^
    PMID 34611326
    .
  65. ^ "Information for clinicians on therapeutic options for COVID-19 patients". US Centers for Disease Control and Prevention. 21 March 2020. Archived from the original on 8 April 2020. Retrieved 22 March 2020.
  66. ^ Hinton DM (28 March 2020). "Request for Emergency Use Authorization For Use of Chloroquine Phosphate or Hydroxychloroquine Sulfate Supplied From the Strategic National Stockpile for Treatment of 2019 Coronavirus Disease" (PDF). U.S. Food and Drug Administration (FDA). Archived from the original on 2 October 2020. Retrieved 30 March 2020.
  67. ^ "Coronavirus Disease 2019 (COVID-19)". Centers for Disease Control and Prevention. 11 February 2020. Archived from the original on 8 April 2020. Retrieved 9 April 2020.
  68. PMID 32208486
    .
  69. ^ "FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems". U.S. Food and Drug Administration (FDA). 24 April 2020. Archived from the original on 4 November 2020. Retrieved 28 February 2021.
  70. ^ Mulier T (17 June 2020). "Hydroxychloroquine halted in WHO-sponsored COVID-19 trials". Bloomberg. Archived from the original on 11 October 2020. Retrieved 17 June 2020.
  71. ^ "No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19". Recovery Trial, Nuffield Department of Population Health, University of Oxford, UK. 5 June 2020. Archived from the original on 8 October 2020. Retrieved 7 June 2020.
  72. ^ "Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Chloroquine and Hydroxychloroquine". U.S. Food and Drug Administration (FDA) (Press release). 15 June 2020. Archived from the original on 15 June 2020. Retrieved 15 June 2020.
  73. ^ Lovelace Jr B (15 June 2020). "FDA revokes emergency use of hydroxychloroquine". CNBC. Archived from the original on 11 October 2020. Retrieved 28 February 2021.
  74. ^ "Frequently Asked Questions on the Revocation of the Emergency Use Authorization for Hydroxychloroquine Sulfate and Chloroquine Phosphate" (PDF). U.S. Food and Drug Administration (FDA). 15 June 2020. Archived from the original on 15 April 2021. Retrieved 15 June 2020.
  75. ^ "Clinical Management Protocol for Covid-19 (in Adults)" (PDF). Ministry of Health and Family Welfare. 24 May 2021. Archived (PDF) from the original on 5 December 2021. Retrieved 10 July 2021. "Health ministry issues revised clinical management protocols for Covid-19 amid spurt in cases". Times of India. Press Trust of India. 13 June 2021. Archived from the original on 11 July 2021. Retrieved 10 July 2021.
  76. S2CID 239763031
    . The WHO, the European Medicines Agency, and the IDSA all recommend against the use of ivermectin for treatment of COVID-19, with the NIH stating that there is insufficient data to recommend for or against its use outside the context of a clinical trial.
  77. ^ "WHO advises that ivermectin only be used to treat COVID-19 within clinical trials". Newsroom. World Health Organization. Geneva, Switzerland. 31 March 2021. Retrieved 12 May 2023.
  78. ^ "EMA advises against use of ivermectin for the prevention or treatment of COVID-19 outside randomised clinical trials". News. European Medicines Agency. Amsterdam. 22 March 2021. Retrieved 12 May 2023.
  79. ^ "Why You Should Not Use Ivermectin to Treat or Prevent COVID-19". United States Food and Drug Administration. Consumer Updates. Silver Spring, Maryland: Food and Drug Administration. 10 December 2021. Retrieved 12 May 2023.
  80. ^ "IDSA Guidelines on the Treatment and Management of Patients with COVID-19: Recommendations 23-24: Ivermectin". Infectious Diseases Society of America. IDSA Practice Guidelines. Arlington, Virginia. 11 April 2023. Retrieved 12 May 2023.
  81. PMID 32251768
    .
  82. New York Times. Archived
    from the original on 7 January 2022. Retrieved 23 December 2021.
  83. ^ Langford C (1 September 2023). "Fifth Circuit sides with ivermectin-prescribing doctors in their quarrel with the FDA". Courthouse News Service.
  84. PMID 35726131
    .
  85. PMID 35353979
    .
  86. S2CID 237607620
    .
  87. ^ "Ivermectin: How false science created a Covid 'miracle' drug". BBC News. 6 October 2021. Archived from the original on 8 January 2022. Retrieved 26 December 2021.
  88. ^ Melissa Davey (15 July 2021). "Huge study supporting ivermectin as Covid treatment withdrawn over ethical concerns". The Guardian. Archived from the original on 16 January 2022. Retrieved 12 May 2023.
  89. ^
    PMID 32147628
    .
  90. PMID 32423584
    .
  91. PMID 32243270
    .
  92. PMID 32837750
    .
  93. PMID 31996494
    .
  94. ^ "'Pyramax' drug repurposing?... targets COVID-19 treatment". Doctor's News. Archived from the original on 26 June 2020. Retrieved 25 June 2020.
  95. S2CID 220885187
    .
  96. ^ "COVID-19: Pyramax Enters Phase II Clinical Trial in South Korea". www.pharmanewsonline.com. Archived from the original on 18 August 2020. Retrieved 17 June 2020.
  97. ^ "A Multi-center, Randomized, Double-blind, Parallel, Placebo-Controlled, Phase II Clinical Trial to Evaluate Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients". nedrug.mfds.go.kr. Archived from the original on 6 October 2020. Retrieved 25 June 2020.
  98. ^ "The Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients". ClinicalTrials.gov. Archived from the original on 6 October 2020. Retrieved 10 September 2020.
  99. ^ "COVID-19 Treatment in South Africa". ClinicalTrials.gov. Archived from the original on 6 October 2020. Retrieved 21 September 2020.
  100. ^ "Study of MK-4482 for Prevention of Coronavirus Disease 2019 (COVID-19) in Adults (MK-4482-013)". ClinicalTrials.gov. 25 June 2021. Archived from the original on 19 October 2021. Retrieved 18 October 2021.
  101. ^ "Efficacy and Safety of Molnupiravir (MK-4482) in Hospitalized Adult Participants With COVID-19 (MK-4482-001)". ClinicalTrials.gov. 5 October 2020. Archived from the original on 19 October 2021. Retrieved 18 October 2021.
  102. ^ "Efficacy and Safety of Molnupiravir (MK-4482) in Non-Hospitalized Adult Participants With COVID-19 (MK-4482-002)". ClinicalTrials.gov. 5 October 2020. Archived from the original on 18 October 2021. Retrieved 18 October 2021.
  103. ^ "A Safety, Tolerability and Efficacy of EIDD-2801 to Eliminate Infectious Virus Detection in Persons With COVID-19". ClinicalTrials.gov. Archived from the original on 15 September 2020. Retrieved 10 September 2020.
  104. ^ "The Safety of EIDD-2801 and Its Effect on Viral Shedding of SARS-CoV-2 (END-COVID)". ClinicalTrials.gov. Archived from the original on 10 September 2020. Retrieved 10 September 2020.
  105. ^ "Oral drug blocks SARS-CoV-2 transmission". medicalxpress.com. Archived from the original on 16 January 2021. Retrieved 16 January 2021.
  106. PMID 33273742
    .
  107. ^ Covid antiviral pill can halve risk of hospitalisation Archived 1 October 2021 at the Wayback Machine BBC
  108. ^ Covid antiviral pill halves hospitalisations and deaths, maker says Archived 1 October 2021 at the Wayback Machine The Guardian
  109. ^ "Molnupiravir gets nod for emergency use in India: From how it works to countries who approved it, everything about antiviral pill". Financial Express. 29 December 2022. Archived from the original on 2 January 2022. Retrieved 2 January 2022.
  110. ^
    PMID 32366720
    .
  111. PMID 32022370
    .
  112. PMID 32226821
    .
  113. PMID 21936817
    .
  114. S2CID 236472654
    .
  115. PMID 33063117
    .
  116. PMID 33347311
    .
  117. PMID 32972430
    .
  118. ^ "Japanese flu drug 'clearly effective' in treating coronavirus, says China". 18 March 2020. Archived from the original on 11 October 2020. Retrieved 23 March 2020.
  119. ^ "Coronavirus: Japanese anti-viral drug effective in treating patients, Chinese official says". The Independent. Archived from the original on 9 October 2020. Retrieved 5 April 2020.
  120. ^ "Which Covid-19 drugs work best?". MIT Technology Review. Archived from the original on 5 April 2020. Retrieved 5 April 2020.
  121. ^ "Coronavirus, il Veneto sperimenta l'antivirale giapponese Favipiravir. Ma l'Aifa: "Ci sono scarse evidenze scientifiche su efficacia"". Il Fatto Quotidiano (in Italian). 22 March 2020. Archived from the original on 14 July 2020. Retrieved 23 March 2020.
  122. ^ "AIFA precisa, uso favipiravir per COVID-19 non autorizzato in Europa e USA, scarse evidenze scientifiche sull'efficacia". aifa.gov.it (in Italian). Archived from the original on 8 August 2020. Retrieved 23 March 2020.
  123. RDIF. 30 May 2020. Archived from the original
    on 6 October 2020. Retrieved 31 May 2020.
  124. ^ "Russian Health Ministry approves anti-coronavirus drug Avifavir". BNN Bloomberg. 31 May 2020. Archived from the original on 9 October 2020. Retrieved 31 May 2020.
  125. ^ "Russia plans coronavirus vaccine clinical trials in two weeks". Reuters. 30 May 2020. Archived from the original on 31 October 2020. Retrieved 31 May 2020.
  126. ^ "Glenmark's FabiFlu approved for coronavirus treatment in India, costs Rs 103 per tablet". India Today. 20 June 2020. Archived from the original on 11 October 2020. Retrieved 30 June 2020.
  127. ^ Swift R (18 February 2021). Feast L (ed.). "Fujifilm's Avigan shows no significant benefit on COVID-19 mortality: study". Reuters. Tokyo. Archived from the original on 25 April 2021. Retrieved 25 April 2021.
  128. PMID 34040117
    .
  129. PMID 32198291
    .
  130. ^
    S2CID 216325781. Archived
    from the original on 14 September 2020. Retrieved 27 March 2020.
  131. PMID 32305088
    .
  132. ^
    PMID 32187464
    .
  133. ^ "Antiviral Drug Combo Ineffective Vs. Coronavirus". WebMD. 20 March 2020. Archived from the original on 23 March 2020. Retrieved 23 March 2020.
  134. ^ Brown J (20 March 2020). "Colorado researchers are racing to find an antiviral drug that could save people with the new coronavirus". Archived from the original on 23 March 2020. Retrieved 23 March 2020.
  135. ^ a b Devlin H, Sample I (19 March 2020). "What are the prospects for a COVID-19 treatment?". The Guardian. Archived from the original on 9 October 2020. Retrieved 23 March 2020.
  136. ^ a b "No clinical benefit from use of lopinavir-ritonavir in hospitalised COVID-19 patients studied in Recovery" (PDF). Recovery Trial. 29 June 2020. Archived (PDF) from the original on 6 October 2020. Retrieved 30 June 2020.
  137. S2CID 222135901
    .
  138. S2CID 222217607
    .
  139. ^ "NIHR funds community COVID-19 antiviral trial". www.nihr.ac.uk. Archived from the original on 16 March 2022. Retrieved 16 March 2022.
  140. ^ "Thousands needed to try a new Covid antiviral treatment". BBC News. 25 January 2022. Archived from the original on 16 March 2022. Retrieved 16 March 2022.
  141. ^ Pinching J (22 February 2022). "PANORAMIC view of World's largest COVID study". PharmaTimes. Archived from the original on 18 March 2022. Retrieved 16 March 2022.
  142. ^ a b c "Veklury EPAR". European Medicines Agency (EMA). 23 June 2020. Archived from the original on 18 March 2021. Retrieved 8 August 2022. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  143. ^ "Gilead Announces Approval of Veklury (remdesivir) in Japan for Patients With Severe COVID-19" (Press release). Gilead Sciences. 7 May 2020. Archived from the original on 26 June 2020. Retrieved 25 June 2020 – via Business Wire.
  144. PMID 32329520
    .
  145. ^ "Remdesivir". Drugs.com. 20 April 2020. Archived from the original on 16 April 2020. Retrieved 30 April 2020.
  146. PMID 32336586
    .
  147. ^ "U.S. Food and Drug Administration Approves Gilead's Antiviral Veklury (remdesivir) for Treatment of COVID-19" (Press release). Gilead Sciences, Inc. 22 October 2020. Archived from the original on 23 October 2020. Retrieved 23 October 2020.
  148. ^ Stephens B (18 April 2020). "The Story of Remdesivir". The New York Times. p. A23. Archived from the original on 22 May 2020. Retrieved 11 May 2020.
  149. PMID 26934220
    .
  150. S2CID 216325781. Archived
    from the original on 14 September 2020. Retrieved 27 March 2020.
  151. ^ Yan VC, Muller FL (14 May 2020). "Gilead should ditch remdesivir and focus on its simpler and safer ancestor". Stat. Archived from the original on 12 June 2021. Retrieved 5 July 2020.
  152. ^ "FDA EUA Remdesivir Fact Sheet for Health Care Providers" (PDF). U.S. Food and Drug Administration (FDA). January 2022. Archived from the original on 24 January 2022. Retrieved 23 January 2022. Public Domain This article incorporates text from this source, which is in the public domain.
  153. ^ "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Archived from the original on 18 January 2021. Retrieved 17 January 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  154. ^ a b "Frequently Asked Questions on Olumiant (Baricitinib) for the Treatment of COVID-19" (PDF). U.S. Food and Drug Administration (FDA). 10 May 2022. Archived from the original on 29 July 2021. Retrieved 10 May 2022. Public Domain This article incorporates text from this source, which is in the public domain.
  155. ^ a b "FDA Roundup: May 10, 2022". U.S. Food and Drug Administration (FDA) (Press release). 10 May 2022. Archived from the original on 10 May 2022. Retrieved 10 May 2022.
  156. ^ "Kineret EPAR". European Medicines Agency. 17 September 2018. Archived from the original on 21 July 2021. Retrieved 20 July 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  157. ^ "EMA recommends approval for use of Kineret in adults with COVID-19". European Medicines Agency. 16 December 2021. Archived from the original on 7 January 2022. Retrieved 2 March 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  158. ^ a b "WHO officials enroll first patients from Norway and Spain in 'historic' coronavirus drug trial". CNBC. 27 March 2020. Archived from the original on 12 April 2020. Retrieved 12 April 2020.
  159. ^ a b "REMAP-CAP Trial". REMAP-CAP. Archived from the original on 12 May 2020. Retrieved 8 May 2020.
  160. ^ "Traumakine to be a part of WHO's Solidarity trial investigating potential COVID-19 treatments". Faron Pharmaceuticals (Press release). 27 April 2020. Archived from the original on 12 June 2022. Retrieved 8 May 2020.
  161. S2CID 253578836
    .
  162. PMID 33844996
    .
  163. ^
    PMID 33844998
    .
  164. ^ "CAS-ViewAlert". www.cas.mhra.gov.uk. Archived from the original on 12 April 2021. Retrieved 16 April 2021.
  165. PMID 33471354
    .
  166. ^ "Dexamethasone". The American Society of Health-System Pharmacists. Archived from the original on 31 August 2017. Retrieved 29 July 2015.
  167. PMID 32043986
    . Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS.
  168. PMID 32876694
    .
  169. ^ "Corticosteroids for COVID-19". Living Guidance. WHO. 2 September 2020. Archived from the original on 11 October 2020. Retrieved 2 September 2020.
  170. ^ "Dexamethasone reduces death in hospitalised patients with severe respiratory complications of COVID-19". University of Oxford. 16 June 2020. Archived from the original on 16 June 2020. Retrieved 16 June 2020.
  171. ^ "Steroid drug hailed as 'breakthrough' for seriously ill COVID-19 patients". Reuters. 17 June 2020. Archived from the original on 2 December 2021. Retrieved 18 June 2020.
  172. ^ Ducharme J. "A Low-Cost Steroid Shows Promise for Treating COVID-19. But Take the News With a Grain of Salt". Time. Archived from the original on 18 June 2020. Retrieved 18 June 2020.
  173. S2CID 219965377
    .
  174. PMID 32678530
    .
  175. ^ "Corticosteroids (Including Dexamethasone)". COVID-19 Treatment Guidelines. National Institutes of Health. Archived from the original on 7 July 2020. Retrieved 12 July 2020.
  176. ^ "Q&A: Dexamethasone and COVID-19". World Health Organization (WHO). Archived from the original on 11 October 2020. Retrieved 12 July 2020.
  177. ^ a b "COVID-19 Guideline, Part 1: Treatment and Management". Infectious Diseases Society of America. Archived from the original on 6 October 2020. Retrieved 22 July 2020. Recommendation 4. Among hospitalized patients with severe* COVID-19, the IDSA guideline panel suggests glucocorticoids rather than no glucocorticoids. (Conditional recommendation, Moderate certainty of evidence)
    Remark: Dexamethasone 6 mg IV or PO for 10 days (or until discharge if earlier) or equivalent glucocorticoid dose may be substituted if dexamethasone unavailable. Equivalent total daily doses of alternative glucocorticoids to dexamethasone 6 mg daily are methylprednisolone 32 mg and prednisone 40 mg.
    Recommendation 5. Among hospitalized patients with COVID-19 without hypoxemia requiring supplemental oxygen, the IDSA guideline panel suggests against the use of glucocorticoids. (Conditional recommendation, Low certainty of evidence)
  178. ^ "EMA starts review of dexamethasone for treating adults with COVID-19 requiring respiratory support". European Medicines Agency (EMA) (Press release). 24 July 2020. Archived from the original on 30 January 2021. Retrieved 27 July 2020. Text was copied from this source, copyrighted by the European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  179. ^
    hdl:10665/334125. WHO/2019-nCoV/Corticosteroids/2020.1. Archived
    from the original on 11 October 2020. Retrieved 2 September 2020.
  180. ^ "WHO updates clinical care guidance with corticosteroid recommendations" (Press release). World Health Organization (WHO). Archived from the original on 21 January 2022. Retrieved 23 January 2022.
  181. ^ a b "EMA endorses use of dexamethasone in COVID-19 patients on oxygen or mechanical ventilation". European Medicines Agency (EMA) (Press release). 18 September 2020. Archived from the original on 14 February 2021. Retrieved 21 September 2020. Text was copied from this source, which is copyrighted by the European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  182. PMID 32876694
    .
  183. ^ "A parasitic infection that can turn fatal with administration of corticosteroids". WHO. 17 December 2021. Archived from the original on 12 December 2021. Retrieved 21 February 2021.
  184. PMID 32416070
    .
  185. ^
    PMID 33693506
    .
  186. ^
    medRxiv 10.1101/2020.05.06.20076687v1
    .
  187. ^ a b Clinical Management of COVID-19, Interim Guidance. World Health Organization. 27 May 2020.
  188. ^ "Retracted coronavirus (COVID-19) papers". Retraction Watch. 29 April 2020.
  189. PMID 32847620
    .
  190. ^ "Vitamin C". COVID-19 Treatment Guidelines. 21 April 2021. Archived from the original on 20 November 2021. Retrieved 2 January 2022.
  191. ^ "COVID-19 Treatment Guidelines". U.S. National Institutes of Health. 26 December 2022. Retrieved 18 December 2023.
  192. ^
    PMID 37071316
    .
  193. ^
    PMID 36553979
    .
  194. ^
    PMID 36235869
    .
  195. ^
    PMID 32758429
    .
  196. ^ "Vitamin D". Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health (NIH). 17 July 2020. Archived from the original on 21 February 2021. Retrieved 22 February 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  197. ^
    ISBN 978-1-4731-3942-8. NG187. Archived
    from the original on 3 December 2021. Retrieved 22 February 2021.
  198. S2CID 236997712. Archived
    from the original on 2 December 2021. Retrieved 9 September 2021.
  199. PMID 33751020
    .
  200. PMID 33775818
    .
  201. ^
    PMID 33774074
    .
  202. ^ Evidence reviews for the use of vitamin D supplementation as prevention and treatment of COVID-19 (PDF) (Report). National Institute for Health and Care Excellence (NICE). December 2020. Archived from the original on 20 October 2021. Retrieved 22 February 2021.
  203. ^ a b "International clinical trials assessing vitamin D in people with COVID-19". ClinicalTrials.gov. Archived from the original on 6 October 2020. Retrieved 11 June 2021.
  204. PMID 32535032
    .
  205. ^
    PMID 33486522
    .
  206. S2CID 235202971
    .
  207. PMID 31064117
    .
  208. ^ "Zinc". Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health (NIH). 21 April 2021. Archived from the original on 10 November 2021. Retrieved 28 November 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  209. ^ "Coronavirus: Scientists could repurpose drugs to treat infection". Medical News Today. 28 February 2020. Archived from the original on 17 March 2020. Retrieved 20 March 2020.
  210. ^ "Existing Drugs May Offer a First-Line Treatment for Coronavirus Outbreak". Global Health News Wire (Press release). Archived from the original on 3 May 2020. Retrieved 20 March 2020.
  211. PMID 34870144
    .
  212. PMID 32871342
    .
  213. ^ "Biodefense Strategic Plan". NIH: National Institute of Allergy and Infectious Diseases. 7 August 2015. Archived from the original on 31 January 2021. Retrieved 2 February 2021.
  214. ^ "NIH funds development of new broad-spectrum therapeutics". National Institutes of Health (NIH). 18 September 2015. Archived from the original on 28 January 2021. Retrieved 2 February 2021.
  215. PMID 32179150
    .
  216. ^
    PMID 32081774
    .
  217. ^ "Amid Ongoing COVID-19 Pandemic, Governor Cuomo Accepts Recommendation of Army Corps of Engineers for Four Temporary Hospital Sites in New York". governor.ny.gov. 22 March 2020. Archived from the original on 6 October 2020. Retrieved 24 March 2020.
  218. ^ "Revive Therapeutics Announces U.S. FDA Approval of Confirmatory Phase 3 Clinical Trial for Bucillamine in COVID-19" (Press release). Revive Therapeutics Ltd. 31 July 2020. Archived from the original on 6 October 2020. Retrieved 5 August 2020 – via GlobeNewswire.
  219. ^ a b "Début d'une étude clinique pour tester un médicament contre les effets de la COVID-19 | Coronavirus". Radio-Canada.ca. Archived from the original on 14 April 2020. Retrieved 12 April 2020.
  220. ^ a b "COLCORONA Clinical Trial | Stop COVID-19". Colcorona. Archived from the original on 13 August 2020. Retrieved 1 May 2020.
  221. SSRN 3650499
    .
  222. ^ "Antiviral Drug Reduces COVID-19 Inflammation In 48 Hours, Israeli Study Finds". 24 August 2021. Archived from the original on 28 August 2021. Retrieved 28 August 2021.
  223. ^ "Cholesterol Drug May Downgrade COVID-19 Threat - New Study". 29 July 2020. Archived from the original on 28 August 2021. Retrieved 28 August 2021.
  224. ^ "Phase 1 Trial of ST-001 nanoFenretinide in Relapsed/Refractory T-cell Non-Hodgkin Lymphoma". ClinicalTrials.gov. 5 March 2020. Archived from the original on 29 July 2020. Retrieved 10 September 2020.
  225. ^ "New York clinical trial quietly tests heartburn remedy against coronavirus". Science. 26 April 2020. Archived from the original on 29 April 2020. Retrieved 29 April 2020.
  226. ^ "LIBERATE Trial in COVID-19 (LIBERATE)". ClinicalTrials.gov. Archived from the original on 6 October 2020. Retrieved 10 September 2020.
  227. ^ "Coronavirus: Ibuprofen tested as a treatment". BBC News Online. 3 June 2020. Archived from the original on 6 October 2020. Retrieved 4 June 2020.
  228. PMID 33310766
    . Covid-19 patients with recent influenza vaccination experience better health outcomes than non-vaccinated patients in Brazil.
  229. ^ Ning Q (14 March 2020). "A Pilot Study of Sildenafil in COVID-19". ClinicalTrials.gov. Archived from the original on 4 September 2020. Retrieved 10 September 2020.
  230. ^ "No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19". Recovery Trial, Nuffield Department of Population Health, University of Oxford, UK. 5 June 2020. Archived from the original on 8 October 2020. Retrieved 7 June 2020.
  231. ^ Horby P, Landray M (14 December 2020). "RECOVERY trial finds no benefit from azithromycin in patients hospitalised with COVID-19". RECOVERY Trial. Archived from the original on 8 March 2022. Retrieved 8 March 2022.
  232. ^
    doi:10.1126/science.adb1803
    .

Further reading

External links
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