10 Best Outpatient Treatments for COVID-19 (Updated March 2021)
Even with successful vaccines and other preventable measures in place, the availability of outpatient treatments with solid evidence has a critical role to play in ending this pandemic.
The aim of this article is to compile related information and evidence in an electronic format that can be updated in step with the rapid pace and growing volume of related evidence related to outpatient treatments of COVID-19.
Outpatient treatment administered outside of the hospitalized setting should be under the supervision of a physician or licensed medical professional who is knowledgeable in the use of the medications and the monitoring approach for ambulatory, home-based COVID-19. Patients who worsen in any way should seek emergency room evaluation immediately.
This article will focus on early, ambulatory, home-based medical treatment overseen by your physician, using a combination of available medicines, already FDA-approved for other medical conditions, and widely used in clinical medicine every day.
Most doctors know the need to focus now on early treatment as the most immediate and practical way to reduce hospitalisations and death. This is your guide to help you know your options, and to use with your personal physician.
Below, we look at the top 10 best outpatient treatment categories for COVID-19 and summaries of the rationale and evidence for each category.
“It is true that these rapidly emerging studies demonstrate the power of Ivermectin, are purposed, 40-year-old drug first approved by the World Health Organization (WHO) for treating parasitic infections,” said Dr. Paul Marik, the founder of the FLCCC Alliance, Professor of Medicine and the most highly published Critical Care physician in America.
- A multi-centre randomised controlled study in Egypt (Elgazzar, Research Square) reported that the death rate was significantly lower in Ivermectin treated patients group (severe patients) vs non-Ivermectin group (2% vs 20%). 1,300 patients were included in this randomized controlled trial.
- This randomized controlled trial out of Iran (Hashim, pre-print) used Ivermectin and Doxycycline in mild, moderate, and severe hospitalized COVID-19 patients. No patients in the mild and moderate COVID-19 category died and 18% of the severe patients perished taking this medication combo. In the control group, no mild-moderate patients died, but 27% of the severe COVID patients died. The patients who also got Ivermectin had a shorter recovery.
- A randomized, double-blind, placebo-controlled, multicenter, phase 2 clinical trial at five hospitals (Iran) and 180 patients with mild to severe disease (Niaee, ResearchSquare, Nov 2020). Ivermectin as an adjunct reduced the rate of mortality, the duration of low oxygen saturation, and the duration of hospitalization.
- The ICON study in US, published in Chest, Oct 2020 reported that Ivermectin treatment was associated with lower death rate vs Control (13.3% vs 24.5%) during treatment of COVID-19, especially in patients with severe pulmonary involvement.
- A double-blinded randomised controlled study in Bangladesh (Mahmud et al) reported that the death rate was 0% (0/183) in the Ivermectin arm vs 1.67% (3/180) in the control arm in mild to moderate COVID-19 patients.
- The IDEA (Ivermectin, Dexamethasone, Enoxaparin and Aspirin) study from Argentina reported 1 death out of 167 patients studied. The patient that died was a severe COVID-19 patient that required ventilator support.
- The pre-AndroCoV trial from Brazil reported that early detection of COVID-19 followed by a pharmaceutical approach with different drug combinations (Azithromycin, Hydroxychloroquine, Nitazonide, Ivermectin) yielded irrefutable differences compared to non-treated controls in terms of clinical outcomes, ethically disallowing placebo-control randomized clinical trials in the early stage of COVID-19 due to the marked improvements.
- A retrospective study out of Bangladesh (Khan, Archivos de Bronconeumologia 2020). This retrospective study enrolled a total of 325 from April to June 2020. 248 adult COVID-19 patients were looked at in two groups, 115 received ivermectin plus standard care (SC), while 133 received only standard care (SC). This study showed that Ivermectin was efficient at rapidly clearing SARS-CoV-2 from nasal swabs (median 4 days). This was much shorter than in the COVID-19 patients receiving only SC (15 days) or receiving a combination of three antiviral drugs (7–12 days). In addition, fewer Ivermectin patients developed respiratory distress leading to ICU admission. In fact, with Ivermectin, there was a quick hospital discharge (median 9 days) in 114 out of 115 patients; the one remaining patient had been admitted with advanced disease.
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They recommend the addition of azithromycin or doxycycline with either of the drugs. However, the guideline also stresses the necessity of using zinc and supplemental vitamins D and C:
“Either combination above must also include zinc sulfate or gluconate, plus supplemental vitamin D, and vitamin C. Some doctors also recommend adding a B complex vitamin. Zinc is critical. It helps block the virus from multiplying. Hydroxychloroquine is the carrier taking zinc INTO the cells to do its job.”
- Latest on hydroxychloroquine - did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient.
- In this retrospective observational study of SARS-CoV-2 infected non-hospitalized patients (BMC Infect Dis. 2021 Jan), hydroxychloroquine exposure was associated with a decreased rate of subsequent hospitalization.
- The BCI comprises seven hospitals and eight medical centres, with around 1200 HCW (healthcare workers), covering more than two-thirds of Bulgarian territory. The BCI shared their experience at BCI and suggested that HCQ (hydroxychloroquine) and Zinc could possibly provide protection against infection with SARS-CoV-2 (prophylaxis), and could, if used early, help to control the COVID-19 infection (treatment).
- WHO trial (Solidarity): The interim trial results (NEJM. Dec 2020) reported that remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon regimens appeared to have little or no effect on 28-day mortality or the in-hospital course of COVID-19 among hospitalized patients.
- UK's Recovery Trial (University of Oxford): It concluded that "there is no beneficial effect of hydroxychloroquine in patients hospitalised with COVID-19" and the drug has now been pulled from the trial.
- HCQ (Hydroxychloroquine) is not effective when used very late with high dosages over a long period (RECOVERY/SOLIDARITY), effectiveness improves with earlier usage and improved dosing.
- Early treatment shows positive effects.
- Negative evaluations typically ignore treatment time, often focusing on a subset of late stage studies and did not include zinc.
Based on the AAPS algorithm or flowchart above, nutraceuticals are the first line treatment for mild COVID-19 patients.
- Vitamin D3: 1000–3000 IU/day. Note RDA (Recommended Daily Allowance) is 800–1000 IU/day. The safe upper-dose daily limit is likely < 4000 IU/day. Vitamin D deficiency has been associated with an increased risk of acquiring COVID-19 and from dying from the disease. Vitamin D supplementation may therefore prove to be an effective and cheap intervention to lessen the impact of this disease, particularly in vulnerable populations, i.e. the elderly, those of color and obese. (Amazon)
- Vitamin C: 500 - 1,000 mg BID (twice daily)
- Quercetin: 250 mg daily. It is likely that vitamin C and quercetin have synergistic prophylactic benefit. Quercetin should be used with caution in patients with hypothyroidism and TSH levels should be monitored. (Amazon)
- Melatonin: 6 mg before bedtime (causes drowsiness). (Amazon)
- Zinc: 30 - 40 mg/day (elemental zinc). Zinc lozenges are preferred. (Amazon)
- Ivermectin for prophylaxis in high-risk individuals (> 60 years with co-morbidities, morbid obesity, long term care facilities, etc). 0.2 mg/kg Day 1, Day 3 and then followed by biweekly dosing (one dose every two weeks). (also see ClinTrials.gov NCT04425850). NB. Ivermectin has a number of potentially serious drug-drug interactions. Please check for potential drug interaction at Ivermectin Drug Interactions - Drugs.com. The most important drug interactions occur with cyclosporin, tacrolimus, anti-retroviral drugs, and certain anti-fungal drugs.
- Vitamin D3 — 4000 IU/day. (Amazon)
- Vitamin C: 500 - 1,000 mg BID (twice daily) (Amazon)
- Quercetin: 250 mg twice a day. (Amazon)
- Melatonin: 10 mg before bedtime (causes drowsiness). (Amazon)
- Zinc: 100 mg/day. Zinc lozenges are preferred. (Amazon)
- Ivermectin: 0.2 mg/kg per dose. One dose daily - minimum 2 days, maximum 5 days.
- Aspirin: 325 m/day unless contraindicated.
- Pulse oximeter: FLCCC also recommend monitoring your oxygen saturation with a pulse oximeter and to go to the hospital if you get below 94%.
Hydroxychloroquine (HCQ) 200mg once a day for 5 days, then HCQ 200-400mg one time a week (ScienceDirect)
Vitamin C 1000mg once a day (Amazon)
Zinc 25-50mg/day (Amazon)
Ivermectin 0.2 mg/kg — one dose on day 1 and day 3, then take one dose weekly (ivmmeta.com).
Vitamin D3 5000 IU/day or 50000 IU once a week
Vitamin C 1000mg once a day
Treatment Protocol for Low risk patients - over the counter options:
2.2. Epigallocatechin-gallate (EGCG) 400mg 1 time a day for 7 days (J. Agric. Food Chem. 2014)
Treatment Protocol for Moderate / High risk patients
Hydroxychloroquine (HCQ) 200mg 2 times a day for 5-7 days (ScienceDirect)and/or
Ivermectin 0.4-0.5mg/kg/day for 5-7 days (ivmmeta.com).
Either or both HCQ and IVM can be used, and if one only, the second agent may be added after about 2 days of treatment if obvious recovery has not yet been observed etc.
If HCQ is not available, Quercetin 500mg 3 times a day for 7 days OR
EGCG 400mg 2 times a day for 7 days
In combination with the above (AND):
1. Elemental Zinc 50 - 100 mg 1 time a day for 7 days (Amazon)
2. Hydroxychloroquine (HCQ) 200mg 2 times a day for 7 days
3.1. Azithromycin 500mg 1 time a day for 5 days or
3.2. Doxycycline 100mg 2 times a day for 7 days
4. Vitamin C 1000 mg 1 time a day for 7 days (Amazon)
5. Vitamin D3 10,000 IU 1 time a day for 7 days (Amazon)
4. Bamlanivimab and Casirivimab plus Imdevimab (Monoclonal Antibodies)
Regeneron became more widely known when it was used to treat former President Donald Trump after he tested positive for COVID-19.
Both monoclonal antibody therapies have shown promise for clearing the SARS-CoV-2 virus that causes COVID-19 and reducing illness when patients receive the medication within days of their first symptoms.
|Credit: US NIH|
BLAZE-1 (NCT04427501) is a randomized, double-blind, placebo-controlled Phase 2/3 study designed to assess the efficacy and safety of bamlanivimab alone or bamlanivimab and etesevimab together for the treatment of symptomatic COVID-19 in the outpatient setting. To be eligible, patients were required to have mild or moderate symptoms of COVID-19 as well as a positive SARS-CoV-2 test based on a sample collected no more than three days prior to drug infusion.
In the Phase 2 portion of BLAZE-1, cohorts of mild to moderate recently diagnosed COVID-19 patients, were randomized to one of three doses of bamlanivimab (700 mg, 2800 mg, and 7000 mg), bamlanivimab 2800 mg plus etesevimab 2800 mg, or placebo. Results from the Phase 2 cohorts of BLAZE-1 were published in the New England Journal of Medicine and The Journal of the American Medical Association.
In the Phase 3 portion of BLAZE-1, the combination therapy arms enrolled mild to moderate, recently diagnosed COVID-19 patients who are at high risk for progressing to severe COVID-19 and/or hospitalization, studying bamlanivimab 2800 mg plus etesevimab 2800 mg versus placebo, and bamlanivimab 700 mg plus etesevimab 1400 mg versus placebo. The primary outcome measure for the Phase 3 portion of the BLAZE-1 trial was the percentage of participants who experience COVID-related hospitalizations or death from any cause by day 29. The key secondary endpoints were change from baseline to day 7 in SARS-CoV-2 viral load, persistently high SARS-CoV-2 viral load on day 7, time to sustained symptom resolution, and COVID-related hospitalization, ER visit or death from any cause from baseline by day 29. Additional endpoints include change from baseline in viral load at other time points, symptom improvement, symptom resolution, as well as safety.
The study is ongoing with additional treatment arms.
5. Zinc and COVID-19
As of March 2021, there are more than 50 studies that have been launched to investigate the benefits of Zinc against COVID-19. You can review the status of these trials on clinicaltrials.gov.
Excessive doses may interfere with copper absorption, which could negatively affect your immune system as it can cause copper deficiencies, blood disorders, impair the absorption of antibiotics and potentially permanent nerve damage or loss of smell.
Zinc competes with copper for intestinal absorption. Therefore, do not take zinc supplements and copper supplements at the same time. It is best to space doses of these products 2 hours apart, to get the full benefit from each dietary supplement.
|Image credit: ClevelandClinic|
Budesonide is a steroid sold under the trade name Pulmicort by AstraZeneca Plc and is also used for treating smoker's lung. The 28-day study of 146 patients suggested that those who inhaled budesonide reduced the risk of urgent care or hospitalization by 90 per cent when compared with usual care.
The steroid budesonide is sold under the trade name Pulmicort by AstraZeneca Plc and is also used for treating smoker's lung
Researchers said the trial was inspired by the fact that patients with chronic respiratory disease, who are often prescribed inhaled steroids, were significantly under-represented among hospitalized COVID-19 patients during early days of the pandemic.
Initial data from the study also found volunteers treated with budesonide had a quicker resolution of fever and fewer persistent symptoms.
Professor Mona Bafadhel, who led the trial, said: 'There have been important breakthroughs in hospitalised COVID-19 patients, but equally important is treating early disease to prevent clinical deterioration and the need for urgent care and hospitalisation, especially to the billions of people worldwide who have limited access to hospital care.
'The vaccine programmes are really exciting, but we know that these will take some time to reach everyone across the world.
'I am heartened that a relatively safe, widely available and well studied medicine such as an inhaled steroid could have an impact on the pressures we are experiencing during the pandemic.'
Results from the Oxford University study are yet to be published in a peer-reviewed journal.
Azithromycin is a widely prescribed generic antibiotic. While it's mainly used to fight bacteria, not viruses, there is some research suggesting the drug has antiviral properties.
As of March 2021, there are more than 120 studies that have been launched to investigate the benefits of Azithromycin against COVID-19. You can review the status of these trials on clinicaltrials.gov. Several trials are testing azithromycin in combination with hydroxychloroquine.
One potential concern is serious heart side effects. Both drugs can cause abnormal changes in the rhythm of the heart. These can be fatal, particularly for susceptible patients who already have heart problems. Many studies are using EKG tests to closely monitors patients receiving this treatment combination.
While QT-prolonging medication use has been associated with increased risk of death, this risk may be smaller than the potential benefit from treatment of COVID-19 for some patients (American College of Cardiology).
8. Povidone Iodine and COVID-19Povidone iodine (PVP-I) is an antiseptic that has been used for over 150 years. It's already proven that different concentration of PVP-I can deactivate COVID-19 virus.
Povidone Iodine COVID-19 Studies
We have compiled a list of povidone iodine COVID-19 studies below:
Feb 2021 - Guenezan et al., JAMA Otolaryngol Head Neck Surg., doi:10.1001/jamaoto.2020.5490 (Peer Reviewed)
Povidone Iodine Mouthwash, Gargle, and Nasal Spray to Reduce Nasopharyngeal Viral Load in Patients With COVID-19: A Randomized Clinical Trial
RCT of PCR+ patients with Ct<=20 with 12 treatment and 12 control patients, concluding that nasopharyngeal decolonization may reduce the carriage of infectious SARS-CoV-2 in adults with mild to moderate COVID-19. All patients but 1 had negative viral titer by day 3 (group not specified). There was no significant difference in viral RNA quantification over time. The mean relative difference in viral titers between baseline and day 1 was 75% [43%-95%] in the intervention group and 32% [10%-65%] in the control group. Thyroid dysfunction occurred in 42% of treated patients, with spontaneous resolution after the end of treatment. Patients in the treatment group were younger.
Dec 2020 - Choudhury et al., Bioresearch Communications, Volume 7, Issue 1, January 2021 (Peer Reviewed)
Effect of 1% Povidone Iodine Mouthwash/Gargle, Nasal and Eye Drop in COVID-19 patient
RCT 606 patients in Bangladesh for povidone iodine mouthwash/gargle, nasal drops and eye drops showing significantly lower death, hospitalization, and PCR+ at day 7.
In Vitro Efficacy of a Povidone-Iodine Nasal Antiseptic for Rapid Inactivation of SARS-CoV-2
In Vitro study showing povidone-iodine nasal antiseptics at concentrations (0.5%, 1.25%, and 2.5%) completely inactivated SARS-CoV-2 within 15 seconds of contact. No cytotoxic effects on cells were observed after contact with each of the nasal antiseptics tested.
Early viral cleerance among COVID-19 patients when gargling with povidone-iodine and essential oils: a pilot clinical trial
Tiny RCT with 5 PVP-I patients, gargling 30 seconds, 3x per day, and 5 control patients (essential oils and tap water were also tested), showing improved viral clearance with PVP-I.
June 2020 - Hassandarvish et al., Nature's British Dental Journal volume, doi:10.1038/s41415-020-1794-1 (Peer Reviewed) (In Vitro)
Povidone iodine gargle and mouthwash
In Vitro study showing undiluted PVP-I (1% w/v) achieved >5 log10 reduction in SARS-CoV-2 virus titres at 15, 30 and 60 seconds treatment exposure under both clean and dirty conditions. In contrast, when PVP-I was tested at 1:2 dilution a >4 log10 kill at 15 seconds and >5 log10 kill at 30 and 60 seconds in comparison to control was seen in both clean and dirty conditions.
9. Vitamin D and COVID-19Based on several publications and studies, vitamin D seems to be the “most promising” supplement for COVID-19 protection. Many studies have showed the link between vitamin D deficiency and COVID-19. However, the causal relation between the two is still unclear.
Of those with a vitamin D level below 20 ng/ml (deficiency), 12.5% tested positive for SARS-CoV-2, compared to 8.1% of those who had a vitamin D level between 30 and 34 ng/ml (adequacy) and 5.9% of those who had an optimal vitamin D level of 55 ng/ml or higher.
Another study, published in JAMA (JAMA Netw Open - Sep 2020) found that persons who are likely to have deficient vitamin D levels at the time of COVID-19 testing were at substantially higher risk of testing positive for COVID-19 than were persons who were likely to have sufficient levels.
The same team above, has also published a preprint article: A study at the University of Chicago of over 4,000 patients that found that untreated vitamin D deficiency was associated with an increased risk for COVID-19 infection.
According to the Association of American Physicians and Surgeons’ home-based guide to treating COVID-19, vitamin D, C and zinc are necessary.
Some doctors also recommend adding a B complex vitamin. Zinc is critical. It helps block the virus from multiplying. Hydroxychloroquine is the carrier taking zinc INTO the cells to do its job.
To maintain healthy levels, only 400 to 800 IU (15 to 20 mcg) of vitamin D is required daily, but, to boost low levels, higher doses, such as 2,000 IU daily, are used and are generally safe.
10. Aspirin, Antiplatelet agents and antithromboticsIn addition to the obvious symptoms that COVID patients get such as fever and cough during the initial viral phase, they may also get symptoms and signs related to two distinct processes i.e. hyperinflammation (with out without cytokine storm) and a hypercoagulable state. A hypercoagulable state is the medical term for a condition in which there is an abnormally increased tendency toward blood clotting (coagulation).
Because thromboxane A2 is markedly upregulated with SARS-CoV-2 infection, early administration of aspirin 325 mg per day is advised for initial antiplatelet and anti-inflammatory effects (Chow et al., 2020; Glatthaar-Saalmüller et al., 2017; Turshudzhyan, 2020; A. Gupta et al., 2020a).
In a retrospective study of 2773 COVID-19 inpatients, 28% received anticoagulant therapy within 2 days of admission, and despite being used in more severe cases, anticoagulant administration was associated with a reduction in mortality, HR = 0.86 per day of therapy, 95% CI: 0.82-0.89; P<< 0.001. Pre-emptive use of low molecular weight heparin or novel anticoagulants have been associated with >> 50% reduction in COVID-19 mortality (Billett et al., 2020).
Finally, many acutely ill outpatients also have general indications or risk for cardioembolic/venous thromboembolic prophylaxis applicable to COVID-19 (Moores et al., 2020; Ruocco et al., 2020). There are ambulatory randomized trials of aspirin and novel oral anticoagulants underway. However, given reports of catastrophic stroke and systemic thromboembolism and the large reductions in mortality for both prophylactic and therapeutic use, administration of aspirin 325 mg po qd for all COVID-19 high-risk patients and systemic anticoagulation is prudent in patients with a history of heart, lung, kidney, or malignant disease (Yamakawa et al., 2020).