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 COVID-19 Outpatient treatment guidelines below are based on the AAPS (American Association of Physicians and Surgeons). 

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.

Credit: c19early.com

Below, we look at the top 10 best outpatient treatment categories for COVID-19 and summaries of the rationale and evidence for each category.

1. Ivermectin and COVID-19

As of March 2021, there are more than 50 on-going trials on Ivermectin registered on ClinicalTrials.gov.

A pilot study published in the Lancet on January 19, 2021 showed some promising results but the authors concluded that the study warrants further exploration under larger trials with clinical outcomes in patients with risk factors or more severe disease. 

In the absence of definitive large scale trial evidence for outpatient treatment, even a small evidence is worthy of consideration.

The Critical Care physicians of the FLCCC Alliance conducted a comprehensive review of the rapidly emerging scientific evidence on Ivermectin from studies conducted around the world. (The link to their review is HERE.) This review led the team to develop the I-Mask+ Protocol and to call for its urgent adoption by health authorities — who could subsequently issue immediate guidance for the nation’s prescribing physicians.

“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.

Related Publications:
  • 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.
Outpatient Treatment - AAPS protocol:
outpatient treatment COVID-19
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According to the Association of American Physicians and Surgeons’ home-based guide to treating COVID-19, hydroxychloroquine and ivermectin are antiviral agents that “must be started quickly at STAGE I (Days 1 to 5)” and “These medicines stop the virus from (1) entering the cells and (2) from multiplying once inside the cells, and they reduce bacterial invasion in the sinuses and lung.”

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.”


2. Hydroxychloroquine and COVID-19

We have combined hydroxychloroquine and chloroquine under 1 category. Hydroxychloroquine, a less toxic derivative of Chloroquine is a widely used medication by people with lupus or arthritis. It was first approved in the 1950s. Chloroquine is used to treat and prevent malaria and amebiasis.

In general, hydroxychloroquine has not been associated with improved survival among hospitalized COVID-19 patients in the majority of observational studies. Do take note that for some of these studies, hydroxychloroquine was given late or was not combined with zinc. However, 'EARLY' treatment with hydroxychloroquine AND 'zinc' shows promising results instead.

Although results have been mixed, some of the significant ones have been published as covered below.
  • Latest on hydroxychloroquine - 
  • The Spanish BCN-PEP-CoV2 post-exposure therapy with hydroxychloroquine (NEJM. Feb 2021) reported that 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.
Update on hydroxychloroquine - According to a real time meta-analysis of 219 hydroxychloroquine studies:
  • 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.

3. Dietary Supplements (Vitamin D, C, Zinc, Quercetin) and COVID-19 - AAPS Nutraceutical Bundle

Based on the AAPS algorithm or flowchart above, nutraceuticals are the first line treatment for mild COVID-19 patients.

There are more than 70 types of supplements that are being tested for COVID-19. You can review the details of these trials on clinicaltrials.gov. There are more than 120 trials testing the various nutrients and dietary supplements including vitamin D, vitamin C, zinc and melatonin. Vitamin D remains the most tested vitamin followed by vitamin C, for COVID-19.

Quercetin, Hydroxychloroquine, EGCG and Zinc are among the handful of COVID-19 treatments that are being studied as potential candidates that might influence the outcome in the prevention and management of COVID-19. Hydroxychloroquine, Quercetin and EGCG (EpiGalloCatechin Gallate) are all zinc ionophores. Meaning they all transport zinc into the cells.

For prevention, the Front Line COVID-19 Critical Care Working Group, FLCCC recommends (updated Feb 25, 2021):
  • 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. 
For early outpatient protocol (COVID-19 positive), the Front Line COVID-19 Critical Care Working Group, FLCCC recommends (updated Feb 25, 2021):
  • 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%.
The medical evidence to support each drug and nutrient can be found under “Medical Evidence” on the FLCCC’s website.

A word about quercetin: Some physicians are recommending this supplement to reduce viral illnesses because quercetin acts as a zinc ionophore to improve zinc uptake into cells. It is much less potent than HCQ (hydroxychloroquine) as a zinc transporter, and it does not reach high concentrations in lung cells that HCQ does. Quercetin may help reduce risk of viral illness if you are basically healthy. But it is not potent enough to replace HCQ for treatment of COVID once you have symptoms, and it does not adequately get into lung tissue unless you take massive doses (3-5 grams a day), which cause significant GI (gastrointestinal) side effects such as diarrhea.

Prevention Protocol for Moderate / High Risk Patients:

Hydroxychloroquine (HCQ) 200mg once a day for 5 days, then HCQ 200-400mg one time a week (ScienceDirect)

Vitamin D3 5000 IU/day or 50000 IU once a week (Amazon)
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
Quercetin 500mg/day
Zinc 25-50mg/day

Treatment Protocol for Low risk patients - over the counter options:

1. Elemental Zinc 50mg 1 time a day for 7 days (PubMed) (Amazon)

2.1. Quercetin 500mg 2 times a day for 7 days (PubMed) (AmazonOR

2.2. Epigallocatechin-gallate (EGCG) 400mg 1 time a day for 7 days (J. Agric. Food Chem. 2014)

3. Vitamin C 1000mg 1 time a day for 7 days (Amazon)
4. Vitamin D3 5000iu 1 time a day for 7 days (Amazon)

Dr Zelenko Protocol When to Start: Treat patients based on clinical suspicion as soon as possible, preferably within the first 5 days of symptoms. Perform PCR testing, but do not withhold treatment pending results.

Treatment Protocol for Moderate / High risk patients

Hydroxychloroquine (HCQ) 200mg 2 times a day for 5-7 days (ScienceDirect)

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)

Note: The dosages for prevention and treatment protocols are different as the risks and benefits are different for the respective situations. Prevention protocol is for those who are not COVID-19 positive and the treatment protocol is for those who are COVID-19 positive. Do take note that 'early' treatment is important for the best possible outcome.

4. Bamlanivimab and Casirivimab plus Imdevimab (Monoclonal Antibodies)

In the earliest stages of infection, before the host has mounted an effective immune response, anti-SARS-CoV-2 antibody-based therapies may have their greatest likelihood of having an effect. In this regard, although there are insufficient data from clinical trials to recommend either for or against the use of any specific therapy in this setting, preliminary data suggests that outpatients may benefit from receiving anti-SARS-CoV-2 monoclonal antibodies early in the course of infection. 

Two monoclonal antibody therapies were approved for emergency use authorization for outpatients to treat mild to moderate new coronavirus disease in certain high-risk patients by the U.S. Food and Drug Administration in November 2020 — bamlanivimab from Eli Lilly and Co. and Regeneron, which combines the two monoclonal antibodies casirivimab and imdevimab.

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. 

There is some confusion among members of the public, thinking that they are similar to vaccine. Monoclonal antibody is a 'treatment' for COVID-19, not preventive. Monoclonal antibodies are not the same as the COVID-19 vaccine rolling out right now.

Credit: US NIH

March 10, 2021 Update: Eli Lilly and Company (NYSE: LLY) today announced new data from the randomized, double-blind, placebo-controlled BLAZE-1 Phase 3 study, demonstrating bamlanivimab (LY-CoV555) 700 mg and etesevimab (LY-CoV016) 1400 mg together significantly reduced COVID-19 related hospitalizations and deaths ("events") in high-risk patients recently diagnosed with COVID-19. These results provide additional efficacy and safety data that support the use of the dose recently granted both Emergency Use Authorization by the U.S. Food and Drug Administration (FDA) and a positive scientific opinion by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP).

Do take note that bamlanivimab and etesevimab are relatively expensive and are authorised under emergency use for outpatient setting and NOT for those who are hospitalised. 

About BLAZE-1

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

This is one of the most important nutraceutical component of most prevention and treatment protocols. Zinc ionophores like hydroxychloroquine, quercetin, green tea extract (EGCG) given alone are unlikely to be effective without zinc.

Zinc has already been shown in a lab study to inhibit regular coronavirus (not the current SARS-CoV-2) in a 2010 publication.

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.

At the Cleveland Clinic, researchers are enrolling people into a study to see if zinc or vitamin C — or a combination of the two — can reduce the duration of COVID-19 symptoms. Patients will be given the supplements after they have tested positive for COVID-19.

study in Spain (Gonzalez, The Lancet preprint, Oct 2020) among people hospitalised with COVID-19 found that having very low blood levels of zinc was associated with more severe disease and higher mortality rates. This research has not been peer-reviewed, so it should be viewed with some caution.

Taking zinc long term is typically safe for healthy adults, as long as the daily dose is under the set upper limit of 40 mg of elemental zinc (PubMed).

Be aware that typical daily doses of zinc provided by zinc lozenges generally exceed tolerable upper limits for zinc, and for this reason, they should not be used for longer than about a week. 

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.

The ideal dose for prevention while the COVID-19 risk is high is 40-100 mg/d, a portion of which comes from zinc lozenges to spread the zinc through the tissues of the nose, mouth and throat. It should be accompanied by at least 1 mg copper from food and supplements for every 15 mg zinc. 

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.

Do take note that you should keep the dosage back to within 40 mg/d once the exposure risk is back to normal.

6. Inhaled Budesonide and COVID-19

In 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 (hpercoagulability).

cytokine storm and COVID-19
Image credit: ClevelandClinic

A commonly used asthma drug cuts the need to send COVID patients to hospital by 90 per cent and shortens recovery times, Oxford University said today. 

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.

Editor's Note: Inhaled budesonide is part of the AAPS protocol (above) and is recommended when you have breathing or respiratory problems.

7. Azithromycin

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.

In a retrospective cohort study published in the Lancet, it is found that 50% of COVID-19 patients who died had bacterial co-infections in pneumonia. Bacterial coinfections have also been shown to increase the risk of mortality for COVID-19 patients [Chen et al].

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).

In a study on the relationship of faecal bacteria and COVID-19 virus by Petrillo et al, preliminary results suggest that SARS-CoV-2 replicates in bacterial growth medium inoculated with a stool sample from an infected patient and that the replication follows bacterial growth. Although based on a single observation, their results suggest that the COVID-19 virus or parts thereof, is capable of replicating also outside the human body.

8. Povidone Iodine and COVID-19

Povidone 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.

Sep 2020 - Frank et al., JAMA Otolaryngol Head Neck Surg, doi:10.1001/jamaoto.2020.3053 (Peer Reviewed) (In Vitro)
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.

Sep 2020 - Mohamed et al., medRxiv, doi:10.1101/2020.09.07.20180448 (Preprint)
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.

Related: Xlear Nasal Spray with Xylitol, All-Natural Saline Nasal Spray for Sinus Rinse & Sinus Relief > Amazon

9. Vitamin D and COVID-19

Based 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. 

Two studies in France (C Annweiler, Nov 2020G Annweiler, Nov 2020), one in India (A Rastogi, Nov 2020) and one in Spain (M Castillo, Oct 2020) showed that Vitamin D supplementation seems to decrease the mortality rate, the severity of the disease, and the inflammatory markers' levels among the COVID-19 infected patients, leading to a better prognosis and increased survival.

The largest observational study to date, looked at data for 191,779 American patients who were tested for SARS-CoV-2 between March and June 2020 and had had their vitamin D tested sometime in the preceding 12 months.

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.

Data from 14 observational studies — suggest that vitamin D blood levels are negatively correlated with the incidence and/or severity of COVID-19; meaning if your vitamin D level is high, your risk for COVID-19 is low and vice versa.

A study published in November 2020 from Singapore (CW Tan, Nutrition 2020), found that those who were started on a daily oral dose of vitamin D3 (1,000 IU), magnesium (150 mg) and vitamin B12 (500 mcg) within the first day of hospitalisation and continued up to 14 days were significantly less likely to require oxygen therapy and further intensive care.

According to the statement released on 2 October by the U.S. president’s physician said that in addition to the antibodies, Trump “has been taking zinc, vitamin D, famotidine, melatonin and a daily aspirin.”

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.

study early this year of 20 European countries found a link between low levels of vitamin D and higher percentages of COVID-19 cases and mortality. Separately, more than 80% of 200 people hospitalized for COVID-19 in Spain were found to be deficient in vitamin D, according to a study published in October in the Journal of Clinical Endocrinology & Metabolism.

Association of American Physicians and Surgeons' Home-based Guide

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.

Co-Nutrients Reduce Your Vitamin D Requirement

You can minimize your vitamin D requirement by making sure you’re also getting enough magnesium. Magnesium is required for the conversion of vitamin D into its active form and research has confirmed higher magnesium intake helps reduce your risk of vitamin D deficiency by activating more of it. 

Vitamin K2 is another important cofactor, and taking both magnesium and vitamin K2 can lower your vitamin D requirement.

Eggs (44 IU per egg), along with fortified foods including milk and some cereals are excellent sources. 
Do take note that you can also get good amounts of vitamins C and D, zinc and other essential vitamins and minerals from a basic multivitamin. If you are taking a multivitamin, your D-vitamin needs may be covered, but be careful not to let the total exceed 4,000 IU or 100 mcg.

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.

A group of researchers from the US, UK, Netherlands and New Zealand, said that the RDA of vitamin D should be increased to 2,000 IU and vitamin C to 200 mg in their review published in Nutrients 2020.

Vitamin D3 supplements appear to be more effective at raising vitamin D levels than D2 supplements. One should also take vitamin K2 together with D3 as vitamin K2 works synergistically with vitamin D3. 

10. Aspirin, Antiplatelet agents and antithrombotics

In 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).

COVID-19 patients have described chest heaviness associated with the possibility of pulmonary thrombosis (Bhandari et al., 2020). Autopsy studies have described pulmonary micro thrombosis and overt embolism with deep venous thrombus found in over half of fatal COVID-19 cases (Ackermann et al., 2020; Burlacu et al., 2020). These observations support the hypothesis that a unique endothelial injury and thrombosis are playing a role in oxygen desaturation, a cardinal reason for hospitalization and supportive care (Zhang et al., 2020b). 

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-Saalm├╝ller 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).

What's New

Feb 22, 2021 - Japanese study showing that common mouthwashes might help against Covid-19.
Komine et al., Virucidal activity of oral care products against SARS-CoV-2 in vitro

Feb 2, 2021 - Indian prospective controlled study (n=251) of saline nasal spray and gargle shows positive impact on PCR negativity and lung involvement. Many studies with different products now point to the very beneficial impact of that cheap, simple procedure.
Uday Chatterjee, Ajay Chakraborty, Sishir Naskar, Bibhuti Saha, Bhaswati Bandyapadhyay, Subhasis Shee.
Efficacy of normal saline nasal spray and gargle on SARS-CoV-2 for prevention of COVID-19 pneumonia.

Check out this review on a highly navigable website that has continuously updated the evidence-based research on early COVID-19 treatments since June 2020: C19Study.com Review: Early Treatment of COVID-19.


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