Coronavirus Treatment Tracker: 10 Best Treatment Categories for COVID-19 (updated June 2021)

Information related to the COVID-19 ('CO' stands for corona, 'VI' for virus, and 'D' for disease) pandemic has been overwhelming and confusing as well. The information is all over the place and various groups are giving conflicting statements. How do you make sense from all these fragmented information?

As of June 2021, there are more than 5,500 studies that have been launched to investigate various treatments for COVID-19. You can review the details of these trials on ClinicalTrials.gov. New ones are being added every day. The aim of this article is to organise and summarise relevant information in one place. Below, we look at the top 10 most tested and most watched categories.

       
McCullough et al. Reviews in Cardiovascular Medicine, 2020

Update: COVID-19 is a highly dynamic topic. Please refer to the latest FLCCC protocol (April 26, 2021 version).

A summary table analyzing more than 600 studies for COVID-19 treatments (credit: c19early.com)

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

1. Ivermectin and COVID-19

Some doctors and media channels argue that there is very little evidence to support the use of ivermectin to treat COVID-19. However, you can find a summary of the 59 studies on ivermectin done by more than 500 authors from c19ivermectin.com (constantly updated).

As of June 2021, there are more than 80 on-going trials globally on Ivermectin for treatment and prevention of COVID-19 on covid-nma.com.

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 that has been published in a peer-reviewed journal 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.

Appearing as a witness on Dec. 8, 2020, before the Senate Committee on Homeland Security and Governmental Affairs—which held a hearing on “Early Outpatient Treatment: An Essential Part of a COVID-19 Solution”— Dr. Pierre Kory, President of the Frontline COVID-19 Critical Care Alliance (FLCCC), called for the government to swiftly review the already expansive and still rapidly emerging medical evidence on Ivermectin.


2. Dietary Supplements (Vitamin D, C, Zinc, Quercetin) and COVID-19 

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 zinc and vitamin C for COVID-19.

Quercetin, EGCG and Zinc are among the handful of COVID-19 supplements 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 April 26, 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 and obese. (Amazon)
  • Vitamin C: 500 - 1,000 mg BID (twice daily) (Amazon)
  • 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 
    • prevention in high-risk individuals (> 60 years with co-morbidities, morbid obesity, long term care facilities, etc): 0.2 mg/kg per dose (take with or after meals) — one dose today, repeat after 48 hours, then one dose weekly. 
    • Post COVID-19 exposure prevention: 0.2 mg/kg per dose (take with or after meals)  — one dose today, repeat after 48 hours.
For early outpatient protocol (COVID-19 positive), the Front Line COVID-19 Critical Care Working Group, FLCCC recommends (updated Apr 26, 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: 0.2–0.4 mg/kg per dose (take with or after meals) — one dose daily, take for 5 days or until recovered. (Find a Doctor)
  • Fluvoxamine: 50 mg twice daily for 10–14 days. Add to ivermectin if: 1) minimal response after 2 days of ivermectin; 2) in regions with more aggressive variants; 3) treatment started on or after day 5 of symptoms or in pulmonary phase; or 4) numerous co-morbidities/risk factors. Avoid if patient is already on an SSRI (selective serotonin reuptake inhibitor).
  • Nasopharyngeal Sanitation: Steamed essential oil inhalation 3 times a day (i.e. vapo-rub) and/or chlorhexidine/benzydamine mouthwash gargles and Betadine nasal spray 2–3 times a day.
  • 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%. (Amazon)
The medical evidence to support each drug and nutrient can be found under “Medical Evidence” on the FLCCC’s website.

Note: The dosages for prevention and treatment protocols are different as the risks and benefits are different for the respective situation. 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.


3. Bamlanivimab plus Etesevimab, Casirivimab plus Imdevimab and Sotrovimab (Monoclonal Antibodies)

The NIH COVID-19 Treatment Guidelines Panel recommends using one of the following anti-SARS-CoV-2 monoclonal antibodies, listed in alphabetical order, to treat nonhospitalized patients with mild to moderate COVID-19 who are at high risk of clinical progression, as defined by the Emergency Use Authorization (EUA) criteria:
  • Bamlanivimab plus etesevimab; or
  • Casirivimab plus imdevimab; or
  • Sotrovimab.
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 (refer below).


4. 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).

A commonly used asthma drug cuts the need to send COVID-19 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 (Lancet 2021) 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 and is recommended when you have breathing or respiratory problems.

5. 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:

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.

6. Nasal Sprays and COVID-19

Do nasal sprays actually work against COVID-19? 

Below, we've listed the best nasal sprays for COVID-19. Do note that some of them are available as over-the-counter medications but some are still under clinical trial.

1. Nitric Oxide Nasal Spray
2. Iota-Carrageenan Nasal Spray
3. Povidone Iodine Nasal Spray
4. AeroNabs Nasal Spray for COVID
5. Xlear Nasal Spray
6. Taffix Nasal Spray
7. Halberd COVID-19 Preventative Nasal Spray
8. BioBlock®, a Novel Prophylactic Nasal Spray

For more details, check out best nasal sprays for COVID-19.

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

7. Fluvoxamine (Luvox) and Fluoxetine (Prozac) (SSRIs)

Fluvoxamine, developed 40 years ago as an antidepressant —sometimes known as Luvox—has been used mainly to treat obsessive-compulsive disorder (OCD), per the National Alliance on Mental Illness (NAMI). But now, researchers are taking a closer look at how the medication could be an important treatment to prevent patients who test positive for COVID-19 from getting seriously ill with the infection.
Fluvoxamine and COVID-19
In a new interview with 60 Minutes, Angela Reiersen, MD, a child psychiatrist at Washington University in St. Louis—and co-author of a November 2020 study published in the Journal of the American Medical Association (JAMA) regarding the use of fluvoxamine in COVID-19 patients—explained that she first got the idea that the drug could potentially treat COVID-19 after seeing research that fluvoxamine prevented sepsis in mice.

If fluvoxamine isn’t available, fluoxetine is a viable substitute. If you can’t get fluvoxamine, using 30mg once a day of fluoxetine (Prozac) is equally effective (equivalent to 50mg twice a day of fluvoxamine).

8. Proxalutamide (anti-androgen)

Proxalutamide is a non-steroidal anti-androgen — specifically, a selective high-affinity silent antagonist of the androgen receptor — that is under development for the potential treatment of COVID-19, prostate cancer, and breast cancer.

proxalutamide

Kintor Announced on May 18, 2021 (1) FDA Has Greenlighted Proxalutamide’s Phase III Study for Hospitalised Male and Female COVID-19 Patients to Be Conducted; and (2) Inclusion of Female Outpatients in Proxalutamide’s Phase III Study for Mild to Moderate COVID-19.

The phase III trial is a randomized, double-blind, placebo-controlled, multi-regional pivotal trial, designed to evaluate the efficacy and safety of proxalutamide in male outpatients with mild or moderate COVID-19 symptoms. The primary endpoint for the trial is the percentage of hospitalization events (including death) by Day 28. The secondary endpoints of the trial include but not limited to proportion of mortality by Day 28, percentage of patients achieving each clinical status on Days 7, 14 and 28 using National Institute of Allergy and InfectiousDiseases (NIAID) 8-point scoring scale.

9. 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).


10. Vaccine

This is the most watched and anticipated category. Technically, vaccine is not considered a treatment but rather a preventive strategy to boost your immune system and reduce the risk of getting COVID-19.

As of June 2021, researchers are currently testing more than 90 vaccines in clinical trials on humans. The vaccine remains a popular agent for COVID-19 protection, and the published reports of the candidate vaccines showcase some encouraging results.


For COVID-19 vaccine tracker, check out New York Times - Coronavirus Tracker (constantly updated).

Editor's Note: The mRNA and vector-based therapies are not really very new technologies. MRNA and vector-based therapies have been in use since 2012 to treat patients with cancers, inherited immunodeficiencies, metabolic, eye, neuro-muscular diseases, even hypercholesterolemia.

Summary: Treatment Candidates (Alphabetical)

Please send us corrections, updates, or comments. Vaccines and treatments are both extremely valuable and complementary. All practical, effective, and safe means should be used. Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. Denying the efficacy of any method increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateral damage. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. Treatment protocols for physicians are available from the FLCCC.

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