Can Antiviral Supplements Reduce Covid Severity?

Merck recently announced the results of an encouraging study that showed that their oral antiviral drug molnupiravir could prevent death and reduce hospitalization from COVID-19. This is good news, but there may be even better news you haven’t heard about—there are several vitamins, dietary supplements, and natural compounds with antiviral properties that have shown results on par with this drug. These natural approaches are surprisingly effective, safe, inexpensive, and readily available.

While there have not been a head-to-head studies comparing molnupiravir to these natural approaches, in this article we will highlight results from the existing clinical trials as a comparison.

 

Molnupiravir Study Results

There are three key endpoints to compare: mortality (death), hospitalizations, and outcomes in patients who are already hospitalized with severe COVID. Here’s how they stack up.

Merck’s molnupiravir study included 775 people who had had mild to moderate COVID for less than five days. They all had at least one risk factor for poor disease outcome, like obesity, old age, diabetes or heart disease. Molnupiravir successfully reduced death: 8 people in the placebo group died while no one on molnupiravir did. 7.3% of people on molnupiravir had to be hospitalized versus 14.1% of people on the placebo, meaning that the antiviral drug reduces hospitalization by about 48%. Earlier research revealed the more disappointing result that molnupiravir did not benefit people who were already hospitalized with severe disease.

So, the points of comparison are:

1. Molnupiravir reduced death by 100%.
2. Molnupiravir reduced hospitalization by 48%.
3. Molnupiravir was ineffective in patients already in the hospital with severe disease.

How do the natural supplements stack up?

Research on Vitamins C & D for Covid

Perhaps the most studied and promising supplement for COVID is vitamin D3. How does it fare on the key points of comparison?

In a study of hospitalized COVID patients with severe respiratory infection and various comorbidities, while 8% of the group receiving “best available therapy” died, no one receiving active 25-OH-vitamin D3 died. The dose of 25-OH-vitamin D3 was 0.532mg on the first day, 0.266mg on day 3 and 7, and then weekly). While 50% of the control group had to be admitted to ICU, only 2% of the vitamin D treated group did. Like molnupiravir, 25-OH-vitamin D3 completely prevented death. It reduced admission to ICU by 25 times. And it was effective in patients already admitted to hospital with severe disease. These results seem superior to molnupiravir even though the control group in the molnupiravir study only received a placebo while 25-OH-vitamin D3 was being compared to the best therapy the hospital had to offer (J Steroid Biochem Mol Biol 2020 Oct;203:105751).

Several other studies have also demonstrated the ability of vitamin D3 to reduce the chances of COVID. In people with COVID who were asymptomatic or mildly symptomatic, 62.5% became COVID negative on vitamin D3 versus only 20.8% on placebo (Postgraduate Medical Journal Nov 2020;doi:10.1136/postgradmedj-2020-139065).

To be effective, your blood levels of vitamin D3 don’t even need to be optimal: just near normal. The optimal level of 25-OH-vitamin D3 is 50-80 ng/ml. When people who are hospitalized with COVID and severe acute respiratory syndrome had levels of 25-OH-D3 below 25 ng/ml, which indicates a vitamin D deficiency, 85% of them died. When blood levels reached just 34ng/ml, nobody died (Am J Clin Pathol 2021;15(3):381-8).

These studies suggest that oral vitamin D3 seems to produce results as good as or better than molnupiravir on each point of comparison.

What about vitamin C?

In a study of people who had severe acute respiratory syndrome from COVID-19, 36% of the placebo died versus 19% of the vitamin C group. Remember that, unlike the people in the molnupiravir study, this difficult challenge gave vitamin C to people who were severely ill. Among the most critically ill, vitamin C cut deaths from 50% to 18% (Pulmonology 2020;doi:10.21203/ rs.3.rs-52778/v2).

In a second study of 76 people hospitalized with COVID, 5 of 30 in the control group died within 28 days compared to 1 of 46 in the vitamin C group (Aging 2021 Feb 26;13(5):7020-34). Molnupiravir is ineffective in patients like the ones in these two studies who are already hospitalized. The dose of vitamin C in this study was 12g intravenously a day for a week. In the first study it was a lesser 12g on the first day and then 6g for the next 4. We will still have to see if these remarkable results can be achieved by orally attainable doses.

Quercetin

One of the most promising natural products for COVID is quercetin. Detailed molecular docking and in-vitro studies show that quercetin blocks ACE-2 receptors so the COVID virus cannot enter your cells, rendering it impotent. Now two published human studies with Quercetin Phytosome, an enhanced form of quercetin for improved absorption, show results superior to molnupiravir.

In an unblinded study, 152 people with COVID, but not severe symptoms, were given either standard at home care or standard care plus 500 mg of Quercetin Phytosome twice a day for 30. While 28.9% of people in the standard care group had to be hospitalized, only 9.2% of the quercetin group did. Quercetin cut hospitalization by 68%. And when they did have to be hospitalized, the average stay was 6.77 days in the standard care group but only 1.57 days in the quercetin group. 10.5% of the standard care group progressed to a very severe condition that required admission to ICU and 3 of them died, no one on quercetin had to go to ICU, and none of them died (Int J Gen Med 2021;14:2359–2366).

In a seconded unblinded study, 42 people with COVID were treated with either standard care or standard care plus 500 mg of Quercetin Phytosome 3 times a day for the first week and 2 times a day for the second. After one week, 2 people in the standard care group tested negative and 4 had their symptoms partially improved; in the quercetin group, 16 tested negative, and 12 had all their symptoms partially improved. After two weeks, 17 of the remaining 19 on standard care tested negative and one died on day 20; all of the remaining 5 people in the quercetin group tested negative, and no one died (Int J Gen Med 2021;14:2807-2816).

Collective analysis of the two quercetin studies revealed significant risk reduction in need of hospitalization, length of hospitalization, admission to ICU and death (Nature  doi.org/10.1038/s41586-021-03995-1(2021).

As with molnupiravir, quercetin reduced hospitalization and cut deaths to zero.

Black Seed Oil

Black seed (Nigella sativa) oil has also been shown to reduce hospitalization and death. When 173 people with mild COVID symptoms were given either usual care or the same care plus 500mg of black seed oil twice a day for 10 days, a significantly greater 62% of the black seed oil group recovered within 14 days compared to only 36% of the control group. 4 people in the control group (4.6%) had to be hospitalized due to disease complications while only one (1.1%) in the black seed oil group had to be hospitalized (Complement Ther Med 2021 Aug 15;61:102769).

A study of 313 people whose moderate to severe COVID may have been more challenging than the mild to moderate COVID of the molnupiravir study compared a black seeds and honey combination to placebo. People given black seeds recovered faster, and, while 18.87% of the placebo group had died by day 30, only 4% of the black seeds and honey group had (medRxiv November 6, 2020;doi.org/10.1101/2020.10.30.20217364).

Melatonin

A just-published study of melatonin is more difficult to compare because it had different endpoints, but it shows significant beneficial results with melatonin supplementation in hospitalized patients with COVID. In this study, standard care was compared to the same care plus 3mg of melatonin 3 times a day for 14 days. The ones given melatonin had significantly greater improvement in cough, difficulty breathing, fatigue, and pulmonary involvement. They also had lower levels of the inflammatory marker C-reactive protein. The melatonin group were discharged from hospital significantly faster and returned to normal health significantly faster. No one died in either group (Arch Med Res 2021 Jun 23;S0188-4409(21)00141-7). In a subgroup of patients in the same study, melatonin was also shown to reduce inflammatory cytokines and modulate the immune system (Eur J Pharmacol 2021 Aug 5;904:174193).

	Reduction in Death	Reduction in Hospitalization	Effect on Hospitalized Patients with Severe Disease
Molnupiravir	100% in mild-moderate	48% reduction in hospitalization	Ineffective
Vitamin D	100% in severe/hospitalized	96% reduction in admission to ICU	Effective
Vitamin C	48%-88% in severe/hospitalized	Unavailable (already hospitalized)	Effective
Quercetin	100% in mild-moderate	68% reduction in hospitalization 100% reduction in admission to ICU	Not Available
Black Seed	79% in moderate-severe	76% reduction in hospitalization	Not Available. Effective on moderate-severe.

 

Ted Snider contributed to this article.