COVID-19 and Pharmacotherapy

The first chart below provides information or resources on pharmacotherapy of interest for COVID-19, the disease caused by the SARS-CoV-2 virus. Additional resources on pharmacotherapy, which are frequently updated, include:

At this point, no pharmacotherapy has been proven effective for COVID-19, so treatment is largely supportive. Resources pertinent to supportive therapy include:

The second chart below addresses common questions about pharmacotherapy as it relates to COVID-19.

**Search for the latest information on COVID-19 clinical trials.**

Abbreviations: ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; ARDS = acute respiratory distress syndrome; COPD = chronic obstructive pulmonary disease; CT = computed tomography; ECMO = extracorporeal membrane oxygenation; EUA = Emergency Use Authorization; IDSA = Infectious Diseases Society of America; IL = interleukin; NIH = National Institues of Health; NSAIDs = nonsteroidal anti-inflammatory drugs; SARS = severe acute respiratory syndrome; SARS-CoV-2 = the virus that causes COVID-19 disease; tPA = tissue plasminogen activator; TNF = tumor necrosis factor; WHO = World Health Organization



Pertinent Information or Resources
Note that DOSES provided are examples only for ADULTS; the optimal dose has not been determined for any treatment.

Anakinra (Kineret)

Anakinra is an IL-1 antagonist. IL-1 may have a role in ARDS.65

Anakinra 5 mg/kg twice daily intravenously in moderate to severe ARDS (non-ventilator) and inflammation (elevated C-reactive protein and/or ferritin) (n=29) was associated with improved survival compared to a similar historical cohort (90% vs 56%, p = 0.009).65 These patients also received hydroxychloroquine and lopinavir/ritonavir.65 A lower dose of anakinra (100 mg twice daily subcutaneously) did not seem to provide benefit.65


Macrolides have in vitro antiviral (e.g., Zika, Ebola), anti-inflammatory, and immunomodulatory activity.2,7

Insufficient evidence to support widespread use [Evidence level C].2,28

Was used in a small, widely publicized study with hydroxychloroquine in six patients to prevent bacterial superinfection in COVID-19 patients (See hydroxychloroquine, below).2 Subsequent observational data including 74 additional patients suggests that the combination can reduce viral load and perhaps improve the clinical course, but there was no comparator group.28 Also see the hydroxychloroquine section below for information on its use in a U.S. cohort study.75

NIH guidelines recommend against the use of azithromycin plus hydroxychloroquine outside of a clinical trial.50

Studies for COVID-19 treatment include various dosing regimens (usually azithromycin 500 mg x 1 then 250 mg once daily for four days) WITH chloroquine, hydroxychloroquine, or other antimicrobials. See for the latest information on these studies.

When used with hydroxychloroquine or chloroquine (and other QT prolonging medications), QT prolongation is of increased concern.2,4,6


Investigational synthetic form of vasoactive intestinal polypeptide. Has anti-IL-6 and anti-TNF activity. Phase I trial suggests benefit in ARDS. No COVID-19 data.

Clinical trial is planned for COVID-19-associated ARDS. See for more information.

Baloxavir (Xofluza)

No COVID-19 data.

Chloroquine phosphate*

*Chloroquine phosphate
500 mg = chloroquine base 300 mg6


  • Inhibits SARS-CoV-2 in vitro,2 but clinical trials have not shown benefit against other viruses.18 Also has immunomodulating effects.26 Early reports suggested that for COVID-19 pneumonia, it could speed clinical improvement and viral clearance.3
  • The FDA has revoked its EUA for chloroquine because it is unlikely to be effective, based on data from the EUA and elsewhere.73
  • Clinical trials are planned on the use of chloroquine to prevent COVID-19 in healthcare workers.
  • See for regimens being studied.


  • The FDA suggested, as part of their now-revoked EUA for chloroquine, for patients weighing ≥50 kg, a chloroquine phosphate dose of 1 g on day one, followed by 500 mg once daily for four to seven days.4 This suggested dosing regimen is unlikely to produce an antiviral effect.73


  • In addition to efficacy concerns, the FDA's revocation of its EUA for chloroquine was based on adverse effects; its known and potential benefits no longer outweigh the known and potential side effects (e.g., serious cardiac events and other serious side effects).33
  • The FDA recommends against chloroquine use for COVID-19 outside of a clinical trial.33
  • Adverse effects are not well-characterized at the doses studied for COVID-19. In general, potential adverse effects include: gastrointestinal side effects (take with food or milk), headache, hypoglycemia, QT prolongation and other conduction disturbances (especially with hypokalemia, hypomagnesemia, or heart disease), cardiomyopathy, myopathy, movement disorders, neurotoxicity, ocular toxicity, ototoxicity, anemia, thrombocytopenia, neutropenia, bone marrow suppression, serious dermatologic reactions, and psoriasis flare.4,27 Monitor electrolytes, glucose, complete blood count, electrocardiogram, baseline renal and hepatic function, knee and ankle reflexes, vision, and mental status.4,6,27
  • A Brazilian study of chloroquine phosphate 600 mg twice daily vs 450 mg twice daily stopped the high-dose arm due to higher instance of QT prolongation >500 milliseconds (18.9% vs 11.1%) and mortality (39% vs 15%).41 All patients received azithromycin.41
  • When used with azithromycin (and other QT-prolonging medications), QT prolongation is of increased concern.2,6


Based on its anti-inflammatory effect, there is interest in using colchicine to alter the clinical course of COVID-19 in both inpatients and higher-risk outpatients.

The open-label GRECCO-19 study randomized patients to colchicine plus standard care or standard care (n = 105).  The clinical primary endpoint, which included measurements of inflammation and clinical deterioration, occurred in 14% of the control group vs 1.8% in the colchicine group (p=0.02).This study’s findings are considered “hypothesis-generating” only.9

Additional clinical trials are underway. See for more information.

Keep in mind colchicine’s toxicities and drug interactions. See our chart, Colchicine Dosing and Interactions, for details.

Convalescent Plasma (COVID-19)

Small case series in patients hospitalized with severe COVID-19 show promise (e.g., defervescence, radiographic improvement, improved oxygen support requirements, viral clearance, improved clinical condition).62-64 It appears well-tolerated.62-64 Concerns include allergic reactions, fluid overload, transfusion-related lung injury, and viral infections.70

Unpublished data from the Mayo Clinic-led expanded access program found a seven-day mortality rate of 8.7% in patients who received convalescent plasma within three days of diagnosis vs 11.9% in those who received it later (p<0.001). Thirty-day mortality was 21.6% vs 26.7% (p<0.0001). There seemed to be a dose-response relationship between the antibody levels in the transfused plasma and mortality reduction. About half of the 35,322 patients were in critical care units, and 27.5% were receiving mechanical ventilation at the time of transfusion.82

The FDA has issued an emergency use authorization (EUA) for convalescent plasma, in part based on data from the expanded access program.

The EUA does not replace clinical trials.70 Providers are encouraged to enroll patients in a clinical trial.70 See and for more information.

A fact sheet about the EUA for healthcare professionals is available at

A fact sheet explaining how the EUA differs from the discontinued expanded access program is available at

In Canada, convalescent plasma is only being supplied to physicians for use in the context of clinical trials under the authorization of Health Canada.71

Recovered patients interested in donating their plasma can do so through the American Red Cross (, or they can locate a donation center at Mobile blood drives in their area may be another option. In Canada, see


There is concern that corticosteroids have the potential to delay viral clearance, as observed in MERS-CoV and SARS.10 However, they are being studied for COVID-19.

In one institution in China, methylprednisolone use in patients with COVID-19 ARDS was associated with reduced mortality.16 This and other cohort studies were limited by confounding, and inclusion of patients with various disease severities and concomitant treatments.46

Data from the open-label RECOVERY trial, in which 2,104 patients were randomized to oral or intravenous dexamethasone 6 mg/day for 10 days, suggests a mortality benefit for COVID-19 patients requiring oxygen, especially for those requiring ventilation, over usual care (n = 4,321).31 NNT = 8 to prevent one death in ventilated patients, or 34 in patients requiring oxygen but not ventilation. It did not provide a mortality benefit (and may harm) patients not requiring oxygen. It also did not provide a mortality benefit for early disease (symptoms for a week or less). This suggests that dexamethasone’s mechanism involves an anti-inflammatory effect rather than an antiviral effect, because inflammation is more common in advanced disease, while viral replication is at maximum in early disease.

The open-label REMAP-CAP study (n=403) randomized COVID-19 patients admitted to intensive care for respiratory or cardiovascular support to hydrocortisone 50 to 100 mg every six hours for seven days, hydrocortisone started only if shock was clinically evident, or no hydrocortisone.83 Analysis suggests hydrocortisone was probably superior to no hydrocortisone in regard to organ support-free days at 21 days, but the study was stopped early.

The open-label CoDEX study (n=299) randomized COVID-19 patients with moderate to severe ARDS to dexamethasone 20 mg once daily for five days, then 10 mg once daily for five days.84 Ventilator-free survival days through day 28 were greater with dexamethasone (6.6 vs 4, p=0.04). However, 35% of the usual care patients received at least one dose of corticosteroids. Mortality was not affected, but this may be because the study was stopped early after the results of RECOVERY were released.

In the only placebo-controlled study of corticosteroids for COVID-19 (CAPE COVID)(n=149), a hydrocortisone infusion was not superior to placebo in regard to death or need for respiratory support (mechanical ventilation or high-flow oxygen) at day 21.85 However, the study was likely underpowered to show a difference, and was stopped early pending RECOVERY publication.

In a WHO meta-analysis that included the above-described studies plus three others (n=1,703), mortality at 28 days was lower in critically ill patients who received corticosteroids vs those who did not receive them (32% vs 40%)(OR 0.66, 95% CI 0.53 to 0.82, p<0.001).86 Neither choice of corticosteroid (dexamethasone or hydrocortisone) nor days from symptom onset (>7 days vs ≤7 days) seems to affect efficacy. Benefit might be greater in patients not receiving mechanical ventilation. Based on these results, WHO strongly recommends systemic corticosteroids (dexamethasone 6 mg once daily or equivalent, via oral or intravenous route) for seven to ten days for severe/critical COVID-19, with glucose monitoring.87

The IDSA suggests dexamethasone 6 mg/day x 10 days (or until discharge, if earlier), for patients hospitalized with severe COVID-19 (oxygen saturation ≤94% on room air; need for supplementation oxygen, mechanical ventilation, or extracorporeal membrane oxygenation). If dexamethasone is not available, methylprednisolone 32 mg or prednisone 40 mg daily can be used.46 NIH guidelines similarly recommend dexamethasone 6 mg/day for up to 10 days in COVID-19 patients who require oxygen or mechanical ventilation.50 Corticosteroids are not recommended for COVID-19 patients not requiring treatment with supplemental oxygen.46,50

Harms of corticosteroids include hyperglycemia, agitation, confusion, and infection risk.46

Inhaled corticosteroids should be continued in asthma or COPD patients with COVID-19.50 The effect of inhaled corticosteroids on COVID-19 risk, severity, or transmission is unknown.50

  • Ciclesonide (Alvesco) and inhaled budesonide are being studied for treatment of COVID-19, but there is no data on efficacy yet. See for more information.


No data.

Dapagliflozin is being studied in COVID-19 patients with respiratory failure and with hypertension, diabetes, heart disease, or advanced renal disease to prevent organ failure, based on its known renal and cardiac benefit (DARE-19 study).

See for more information.


Interest in famotidine as a COVID-19 treatment stems from observations in China that patients who were taking famotidine who were infected with COVID-19 had better outcomes.55

In a retrospective U.S. study (n = 1,620), famotidine use (10 to 40 mg/day; n = 84) within 24 hours of admission was associated with reduced risk of death or intubation in hospitalized COVID-19 patients.67

The IDSA suggests against use of famotidine for COVID-19 outside of a clinical trial.46 See for more information.



  • Is a more potent inhibitor of SARS-CoV-2 than chloroquine in vitro.2 Also has immunomodulating effects.27
  • The FDA has revoked its EUA for hydroxychloroquine because it is unlikely to be effective, based on data from the EUA and elsewhere.73
  • The hydroxychloroquine arm of the large RECORD study was also stopped due to lack of efficacy.31
  • Early enthusiasm for hydroxychloroquine was based on a widely publicized open-label, randomized study in hospitalized patients testing positive for SARS-CoV-2.2 Six of 26 hydroxychloroquine patients were lost to follow-up: one due to death, three due to intensive care admission, one due to side effects (nausea), and one who left the hospital. Viral clearance at day six was 70% in the 20 remaining hydroxychloroquine patients vs 12.5% of the control patients (n = 16).2 Six treated patients also received azithromycin 500 mg on day one, then 250 mg on days two through five to prevent bacterial infection.2 In the combination group, viral clearance was 100% at day six vs 57.1% in the hydroxychloroquine-alone group.2 Also see subsequent observational data under “Azithromycin,” above.
  • In a pilot study in China, 30 patients were randomized to hydroxychloroquine 400 mg/day (it is unclear if this was divided) for five days, or usual care. There was no difference between groups in viral clearance at day seven, length of stay, or time to defervescence.29 In a study of 62 hospitalized patients with mild disease, 31 patients were randomized to hydroxychloroquine 200 mg twice daily. Time to recovery (defervescence and cough remission) was shortened by about one day in the treatment group. On day six, pneumonia was improved per CT in more patients in the treatment group. Four patients progressed to severe disease, all in the control group.39 A subsequent open-label Chinese study (n=150) randomized patients to usual care or hydroxychloroquine 1,200 mg/day for three days, then 800 mg/day for two (mild to moderate disease) or three weeks (severe disease).42 Viral clearance was similar on days 4, 7, 10, 14, 21, and 28 for the two groups. Hydroxychloroquine did not seem to hasten symptom improvement. Thirty percent of hydroxychloroquine patients had adverse effects.
  • A retrospective French cohort study found no benefit of early hydroxychloroquine administration to 84 hospitalized patients in regard to need for intensive care, or mortality.43
  • Similarly, in a retrospective U.S. Veterans Affairs study (n=368), hydroxychloroquine, alone or with azithromycin, was not associated with reduced need for mechanical ventilation in hospitalized patients. Mortality was higher in patients who received hydroxychloroquine alone vs no hydroxychloroquine.49
  • Other retrospective U.S. studies suggest no benefit. In one (n = 1,376), patients received hydroxychloroquine 600 mg twice daily on day 1, then 400 mg daily for a median of five days. Some patients also received azithromycin or sarilumab. About half of patients began treatment within 24 hours of presentation. Hydroxychloroquine use was not associated with a reduced risk of a composite outcome of death or intubation.60 In another study (n=1,438), neither hydroxychloroquine alone, azithromycin alone, nor the combination was associated with improved in-hospital mortality, but the combination was associated with cardiac arrest.66
  • One large (n = 2,541) retrospective U.S. cohort study found reduced mortality with hydroxychloroquine +/- azithromycin vs usual care.75 Patients received 400 mg twice daily for two doses on day one, then 200 mg twice daily on days two to five. Some patients with high cardiac risk were excluded. Select patients with severe COVID-19 and minimal cardiac risk also received azithromycin 500 mg x 1, then 250 mg daily on days two through five. Hydroxychloroquine was started within 48 hours of hospital admission in almost all patients. This study had several limitations. For example, the outcomes of almost 300 patients were not included in the analysis, and there were differences between treatment groups that could not be adequately adjusted for (e.g., baseline disease severity, other treatments received).
  • The FDA suggested, as part of their now-revoked Emergency Use Authorization for hydroxychloroquine, for hospitalized patients weighing ≥50 kg, a dose of 800 mg on day one, followed by 400 mg once daily for four to seven days.31 This suggested dosing regimen is unlikely to produce an antiviral effect.73
  • The WHO has discontinued the hydroxychloroquine arm of the Solidarity Trial because interim results suggest there is little mortality benefit for hospitalized patients.74
  • Outpatients (n=491) with confirmed or probable COVID-19 were randomized to hydroxychloroquine (800 mg x 1, then 600 mg six to eight hours later, then 600 mg once daily for four days) or placebo, starting within four days of symptom onset.11 Mean age was 40 years, and 68% had no chronic medical conditions. Hydroxychloroquine was not better than placebo at improving symptom severity. At day 14, 24% of hydroxychloroquine patients were still symptomatic, vs 30% of placebo patients (p=0.21). Forty-three percent of hydroxychloroquine patients had side effects, vs 22% of placebo patients. Four hydroxychloroquine patients were hospitalized, and there was one outpatient death in this group. In the placebo group, ten placebo patients were hospitalized, one of which died (p=0.29).
  • Clinical trials are ongoing on the use of hydroxychloroquine to prevent COVID-19 in healthcare workers.
  • See for regimens being studied.


  • In addition to efficacy concerns, the FDA's revocation of its EUA for hydroxychloroquine was based on adverse effects; its known and potential benefits no longer outweigh the known and potential side effects (e.g., serious cardiac events and other serious side effects).33
  • Due to the risk of arrhythmias, the FDA recommends against hydroxychloroquine use for COVID-19 outside of a clinical trial.33
  • Adverse effects are not well-characterized at the doses studied for COVID-19. In general, potential adverse effects include: gastrointestinal side effects (take with food or milk), headache, hypoglycemia, QT prolongation and other conduction disturbances (especially with hypokalemia, hypomagnesemia, or heart disease), cardiomyopathy, myopathy, movement disorders, neurotoxicity, ocular toxicity, ototoxicity, anemia, thrombocytopenia, neutropenia, bone marrow suppression, serious dermatologic reactions, and psoriasis flare.27,31 Monitor electrolytes, glucose, complete blood count, electrocardiogram, baseline renal and hepatic function, knee and ankle reflexes, vision, and mental status.6,27,31
  • When used with azithromycin (and other QT-prolonging medications), QT prolongation is of increased concern.2,6 Information on managing QT prolongation risk in these patients is available at

IL-6 antagonist

Tocilizumab (Actemra) sarilumab (Kevzara); siltuximab (Sylvant).

Anti-IL-6 monoclonal antibody.

Some, but not all, data from China suggests an association between elevated IL-6 and severe COVID-19 disease.18

Some anecdotal reports, case series, and cohort studies suggest benefit for tocilizumab (Actemra). One or two doses of 400 to 800 mg (4 to 8 mg/kg) has been used.18,68

May cause increased infections, neutropenia, thrombocytopenia, and elevated liver enzymes.1,34-38 There are several cases of tocilizumab-associated worsening of COVID-19, perhaps due to immunosuppression, despite an associated reduction in inflammatory markers.80

Not for routine use. Clinical trials are planned or underway for treatment of pneumonia or cytokine storm. See for more information.

Outside of a clinical trial, limit to patients with evidence of cytokine storm (e.g., elevated IL-6, etc), with specialist consultation.44

The manufacturer of Kevzara (sarilumab) has discontinued its U.S. clinical trial in COVID-19 patients requiring mechanical ventilation (n = 194) because it did not meet its primary endpoint (improvement on a disease severity scale) or key secondary endpoints.The results of this study are not yet published.77


Ivermectin has several mechanisms that make it an attractive option for study for prevention and treatment of COVID-19. However, it has not demonstrated clinically significant antiviral efficacy for any virus in humans. Clinical trials are underway.32 See

Janus Kinase Inhibitors (Ruxolitinib [Jakafi], etc)

No data.

Interest based on potential to block IL-6 effects, reduce cytotoxic T cells, and increase regulatory T cells.

NIH guidelines recommend against use, except in a clinical trial.50 See for more information.

Lopinavir/ritonavir (Kaletra)

Lopinavir/ritonavir has not demonstrated anti-SARS-CoV-2 activity in humans.15 Small study suggested benefit (reduced composite endpoint of ARDS or death) for 2003 SARS vs historical control.17

Results from a randomized, open-label study (n=199) suggest it might reduce complications such as acute kidney injury, secondary infections, or need for mechanical ventilation in patients with COVID-19 pneumonia.15 However, time to clinical improvement was not reduced (main outcome measure).15 Gastrointestinal adverse effects may limit use.15,30

There is interest in studying lopinavir/ritonavir earlier in the disease course, or in combination with other medications.15 Use with ribavirin and interferon beta-1b early in the disease course (mean five days from symptom onset) was compared to lopinavir/ritonavir alone in hospitalized patients (n=127).58 In this open-label study, median time to viral clearance was seven days with combination therapy vs 12 days for lopinavir/ritonavir alone.58 Alleviation of symptoms occurred in four days vs eight days, respectively (p<0.0001).58

The WHO has discontinued the lopinavir/ritonavir arm of the Solidarity Trial because interim results suggest no mortality benefit for hospitalized patients.74

Additional clinical trials are planned or underway. See for more information.

Losartan, Telmisartan

Studies in mice suggest that ARBs can reduce lung damage caused by SARS-CoV.13

Clinical trials are underway for treatment of COVID-19. See for more information.


Not expected to be effective against SARS-CoV-2 because SARS-CoV-2 does not use neuraminidase.26

Has been used for COVID-19 pneumonia, but there is no efficacy data.12


Remdesivir has in vitro activity against SARS-CoV-2.40

In a cohort of 53 evaluable patients treated with remdesivir for severe COVID-19 disease, use was associated with clinical improvement in regard to oxygen support requirements in 68% of patients.40 Mortality was 13%, which is less than in other case series and cohorts.40 The most common adverse events were liver enzyme elevation (23%), diarrhea (9%), rash, renal impairment, hypotension (8%), acute kidney injury, atrial fibrillation, multiorgan dysfunction, hypernatremia, and venous thrombosis (6%).40 Causality could not be assessed due to the effects of COVID-19 itself.40 Based on previous data, mild to moderate transaminase elevations are expected with remdesivir.40 Viral load was not evaluated,40 but in a previous case report, virologic improvement was seen.8

Preliminary analysis of a double-blind, placebo-controlled trial (n = 1,063), remdesivir seemed to shorten time to recovery (11 days vs 15 days; p <0.001), but mortality was not statistically different (8% vs 11.6%; p = 0.059).54,72 Similarly, a Chinese study found a nonsignificant trend toward faster recovery.61

Unpublished data from the open-label SIMPLE-Severe study compared remdesivir-treated patients (n=312) to a matched cohort of patients receiving standard care (n=818). About 74% of remdesivir patients recovered by day 14 vs 59% of the standard-care patients. Mortality rate at day 14 was 7.6% in the remdesivir patients vs 12.5% in the standard-treatment group (OR 0.38, 95% CI 0.22 to 0.68, p = 0.001).79

U.S.: Remdesivir (Veklury) is being distributed to select hospitals by the government through Emergency Use Authorization.57 This is a rapidly changing situation. For other potential opportunities for availability, see,, or contact Gilead at 833-445-3230 (GILEAD-0) or

Canada: Remdesivir (Veklury) has received marketing authorization with conditions pending the results of additional clinical trials. Its approved indication is treatment of COVID-19 pneumonia requiring supplemental oxygen in patients ≥12 years of age who weigh ≥40 kg.59 Supplies are limited, but availability should improve in October.

If remdesivir availability is limited at your hospital, the NIH recommends prioritizing use for patients requiring oxygen, but not high-flow oxygen, noninvasive ventilation, mechanical ventilation, or ECMO.50

Coadministration of remdesivir and chloroquine or hydroxychloroquine is not recommended based on in vitro data showing that these drugs might interfere with the metabolic activation and antiviral activity of remdesivir.53 In Simple-Severe, recovery rate at day 14 for patients who received hydroxychloroquine plus remdesivir was lower than in patients who received remdesivir alone (57% percent vs 69%, HR 0.61, 95% CI 0.45 to 0.83, p=0.002). Concomitant hydroxychloroquine use was not associated with increased mortality, but was associated with a higher risk of adverse events.79

Another potential drug interaction involves inhibition of remdesivir elimination from hepatocytes by P-glycoprotein inhibitors. This interaction could result in hepatotoxicity.76


Not potent enough to be effective at safe doses; hematologic toxicity precludes use.26 See lopinavir/ritonavir section for information on combination use.


No data.

Interest based on cardiovascular damage noted in COVID-19 patients and anti-inflammatory effects. Simvastatin might also block viral cell entry.

NIH guidelines recommend against use specifically for COVID-19 treatment outside of a clinical trial.50

See for more information on planned or ongoing studies.

tPA (alteplase)

No data.

Interest based on reports of hypercoagulability in COVID-19 patients.19

Studies underway to treat ARDS in COVID-19 patients.19


Due to evidence of a non-specific protective effect against respiratory infections, BCG vaccine is being studied to prevent COVID-19 disease in healthcare workers. See for more information.

Oral polio vaccine has been mentioned on the internet, but no trials are planned at this time.

Vitamin C

Intravenous vitamin C is being studied for treatment of severe COVID-19 disease based on previous data in sepsis and ARDS. However, there is no clear evidence of benefit even for these conditions.48

Oral vitamin C is being studied for treatment of COVID-19 disease in the outpatient setting, and as prophylaxis.

See for more information on these planned or ongoing studies.

Vitamin D

There is false information circulating that vitamin D is recommended by health officials. Interest in vitamin D stems from its effects on the immune system and pulmonary ACE2 expression. Studies are planned or underway using vitamin D for prevention or as a treatment adjunct. See for more information.


Zinc has in vitro activity against SARS-CoV.47

Studies of oral zinc, alone or in combination (e.g., with vitamin C, vitamin D, hydroxychloroquine [purported to help zinc get inside the cells47], azithromycin) to prevent COVID-19 disease are planned or ongoing.

See for more information.


There is a lot of misinformation regarding COVID-19 on the internet. Use this table to help answer patient questions and correct misconceptions.

Clinical question

Pertinent information or resource

Do ACE inhibitors or ARBs make COVID-19 worse?

The SARS-CoV-2 virus uses ACE2 to enter cells.13 ACE inhibitors and ARBs may upregulate ACE2.13 In theory, these drugs could thereby facilitate virus entry into cells.13 But on the other hand, blocking angiotensin could reduce lung injury.13

No evidence suggests that patients taking an ACEI or ARB are more susceptible to COVID-19 infection, or that these medications worsen outcomes.14,51,52,69 One cohort study even suggests reduced mortality in COVID-19 patients taking them for other indications.51 Furthermore, we know that these drugs benefit patients with diabetic nephropathy and cardiovascular disease, populations at risk of severe COVID-19 disease.13,22

Patients should continue these medications. See statements from:

Can NSAIDs be used in COVID-19-infected patients?

Anecdotal reports regarding worse COVID-19 outcomes in patients taking NSAIDs have spread in the media and on social media, including via a tweet from a French health official.14,23 In 2019, a French report suggested that NSAIDs could worsen infections, mainly Strep, perhaps by masking symptoms.24,25 However, there is currently no reliable clinical data supporting worse outcomes in patients taking NSAIDs or aspirin.14,20 Preclinical data is mixed on the potential effects of NSAIDs on COVID-19 (increased expression of ACE2, which the virus uses to enter cells, vs potential antiviral activity of NSAIDs).14

Patients taking low-dose aspirin should not stop taking it because of COVID-19 concerns.14

Neither the FDA nor Health Canada is advising changes to NSAID use due to COVID-19.20,21

Are any supplements effective for prevention or treatment of COVID-19?

There is no scientific evidence that any alternative remedies can prevent or treat COVID-19, and some products may not be safe.5 See our Natural Medicines database ( for information on efficacy and safety of specific alternative medicines.

Patients are hearing about an oleander extract for COVID-19. Advise them that ingestion of oleander has led to fatal poisonings. All parts of the plant contain cardiac glycosides. Other components have central nervous system depressant effects or strychnine-like actions.81

Several studies are looking at multivitamin/mineral combos as adjuncts for treatment or prevention. See for more information. For information on zinc, vitamin C, and vitamin D see the “Treatments of Interest” chart, above.

Are heartburn drugs effective for treating or preventing COVID-19?

For information on famotidine, see the “Treatments of Interest” chart, above.

Proton pump inhibitor (PPI) use was associated with a higher risk of COVID-19 based on results of an online survey of ~53,000 English-speaking Americans, after controlling for confounders. Risk was higher for patients taking a PPI twice daily vs once daily. H2 blockers did not appear to increase risk. Any increased absolute risk of COVID-19 in PPI users is probably small. If patients ask about PPI use, consider this an opportunity to reevaluate treatment and reinforce COVID-19 preventive measures.78

Does nicotine protect against COVID-19?

In China, there was an unexpectedly low prevalence of smoking among patients hospitalized with COVID-19. Low smoking prevalence among hospitalized COVID-19 patients has also been seen in the U.S.56

Nicotine, through its cholinergic agonist activity, blocks production of inflammatory cytokines such as IL-6.56

There is interest in using nicotine, either as currently available products, or perhaps via nebulization, as an adjunct for COVID-19 treatment.56

Continue to use nicotine replacement products for nicotine users who are hospitalized for COVID-19, and for anyone who desires to quit smoking.56

Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.



Study Quality


Good-quality patient-oriented evidence.*

  1. High-quality RCT
  2. SR/Meta-analysis of RCTs with consistent findings
  3. All-or-none study


Inconsistent or limited-quality patient-oriented evidence.*

  1. Lower-quality RCT
  2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings
  3. Cohort study
  4. Case control study


Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

RCT = randomized controlled trial; SR = systematic review [Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56.]

Project Leader in preparation of this clinical resource (360423): Melanie Cupp, Pharm.D., BCPS; Last modified September 8, 2020.


  1. Product monograph for Kevzara. Sanofi Genzyme. Mississauga, ON L4W 4V9. August 2019.
  2. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label, non-randomized clinical trial. Int J Antimicrob Agents 2020 Mar 20:105949. doi: 10.1016/j.ijantimicag.2020.105949.
  3. Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. BioSci Trends 2020;14:72-3.
  4. FDA. Fact sheet for health care providers emergency use authorization (EUA) of chloroquine phosphate supplied from the strategic national stockpile for treatment of COVID-19 in certain hospitalized patients. Revoked. June 15, 2020. (Accessed March 31, 2020).
  5. NIH. National Center for Complementary and Integrative Health. In the news: coronavirus and “alternative” treatments. (Accessed March 28, 2020).
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Cite this document as follows: Clinical Resource, COVID-19 and Pharmacotherapy. Pharmacist’s Letter/Prescriber’s Letter. April 2020.

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