COVID-19 early treatment: real-time analysis of 2,617 studies

All studies Early treatment Mortality Early mortality Prophylaxis Prophylaxis mortality Physicians Recent

Analysis of 49 COVID early treatments, approvals in 101 countries, database of 2,603 treatments

Recently added (more..) Zinc Bromhexine Vitamin A Peginterferon Lambda Vitamin D

Asoudeh	250 patients zinc prophylaxis: 57% lower severe cases [p=0.03]
Vila Méndez	191 patient bromhexine early treatment RCT: 67% lower hospitalization [p=0.49] and 7% worse viral clearance [p=0.82]
Lahaye	Vitamin A sufficiency: 23% lower mortality [p=0.02] and 2% lower severe cases [p=0.4]
Kim	14 patient peginterferon lambda late treatment RCT: 200% higher ICU admission [p=1], 25% longer hospitalization [p=0.59], and 12% improved viral clearance [p=1]
Bucurica	11,182 patients vitamin D sufficiency: 28% fewer cases [p<0.0001]

Cost per life saved from NNT in
studies to date c19early.org Mar 2023

Melatonin

9
48%

Vitamin D

60
36%

$10

Vitamin C

34
27%

$12

Alkalinization

4
42%

$18

Ivermectin

48
51%

$22

Zinc

19
29%

$23

HCQ

232
22%

$29

Vitamin A

6
42%

$30

Colchicine

36
35%

$31

Aspirin

55
12%

$33

Curcumin

7
63%

$40

Fluvoxamine

6
47%

$69

Probiotics

8
61%

$99

Famotidine

18
17%

$105

Metformin

46
32%

$172

Antiandrogens

32
38%

$179

Quercetin

4
59%

$188

Nigella Sativa

4
73%

$279

Nitazoxanide

6
42%

$680

Budesonide

9
28%

$887

Favipiravir

32
15%

$1,015

Paxlovid

13
59%

$46,111

Molnupiravir

15
23%

$137,653

Casirivimab/i..

8
40%

$181,694

Remdesivir

44
14%

$208,615

Bamlaniv../e..

10
56%

$301,549

Sotrovimab

9
57%

$442,638

Tixagev../c..

5
38%

$740,002

Conv. Plasma

39
-6%

N/A

Acetaminophen

13
-27%

N/A

Treatment cost times median NNT - details and limitations

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Timeline for when studies showed efficacy - details and limitations. 1.4% of treatments show efficacy.

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Random effects meta-analysis of all studies (pooled effects, all stages). Treatments with ≤3 studies with distinct authors or with <50 control events are shown in grey. Pooled results across all stages and outcomes depend on the distribution of stages and outcomes tested - for example late stage treatment may be less effective and if the majority of studies are late stage this may obscure the efficacy of early treatment. Please see the specific stage and outcome analyses. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments.

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Random effects meta-analysis of early treatment studies (pooled effects). Treatments with ≤3 studies with distinct authors or with <50 control events are shown in grey. Pooled results across all outcomes are affected by the distribution of outcomes tested, please see detail pages for specific outcome analysis. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments.

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Random effects meta-analysis of all mortality results (all stages). Treatments with ≤3 studies with distinct authors or with <25 control events are shown in grey. Pooled results across all stages depend on the distribution of stages tested - for example late stage treatment may be less effective and if the majority of studies are late stage this may obscure the efficacy of early treatment. Please see the specific stage analyses. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments.

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Random effects meta-analysis of early treatment mortality results. Treatments with ≤3 studies with distinct authors or with <25 control events are shown in grey. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments.

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Random effects meta-analysis of prophylaxis studies (pooled effects). Treatments with ≤3 studies with distinct authors or with <50 control events are shown in grey. Pooled results across all outcomes are affected by the distribution of outcomes tested, please see detail pages for specific outcome analysis. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments.

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Random effects meta-analysis of prophylaxis mortality results. Treatments with ≤3 studies with distinct authors or with <25 control events are shown in grey. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments.

LATE TREATMENT
Physician / Team	Location	Patients	HospitalizationHosp.		MortalityDeath
Dr. David Uip ^(*)	Brazil	2,200	38.6% (850)	Ref.	2.5% (54)	Ref.
EARLY TREATMENT - 37 physicians/teams
Physician / Team	Location	Patients	HospitalizationHosp.	ImprovementImp.	MortalityDeath	ImprovementImp.
Dr. Roberto Alfonso Accinelli 0/360 deaths for treatment within 3 days	Peru	1,265			0.6% (7)	77.5%
Dr. Mohammed Tarek Alam patients up to 84 years old	Bangladesh	100			0.0% (0)	100.0%
Dr. Oluwagbenga Alonge	Nigeria	310			0.0% (0)	100.0%
Dr. Raja Bhattacharya up to 88yo, 81% comorbidities	India	148			1.4% (2)	44.9%
Dr. Flavio Cadegiani	Brazil	3,450	0.1% (4)	99.7%	0.0% (0)	100.0%
Dr. Alessandro Capucci	Italy	350	4.6% (16)	88.2%
Dr. Shankara Chetty	South Africa	8,000			0.0% (0)	100.0%
Dr. Deborah Chisholm	USA	100			0.0% (0)	100.0%
Dr. Ryan Cole	USA	400	0.0% (0)	100.0%	0.0% (0)	100.0%
Dr. Marco Cosentino vs. 3-3.8% mortality during period; earlier treatment better	Italy	392	6.4% (25)	83.5%	0.3% (1)	89.6%
Dr. Jeff Davis	USA	6,000			0.0% (0)	100.0%
Dr. Dhanajay	India	500			0.0% (0)	100.0%
Dr. Bryan Tyson & Dr. George Fareed	USA	20,000	0.0% (6)	99.9%	0.0% (4)	99.2%
Dr. Raphael Furtado	Brazil	170	0.6% (1)	98.5%	0.0% (0)	100.0%
Dr. Heather Gessling	USA	1,500			0.1% (1)	97.3%
Dr. Ellen Guimarães	Brazil	500	1.6% (8)	95.9%	0.4% (2)	83.7%
Dr. Syed Haider	USA	4,000	0.1% (5)	99.7%	0.0% (0)	100.0%
Dr. Mark Hancock	USA	24			0.0% (0)	100.0%
Dr. Mollie James	USA	3,500	1.1% (40)	97.0%	0.0% (1)	98.8%
Dr. Roberta Lacerda	Brazil	550	1.5% (8)	96.2%	0.4% (2)	85.2%
Dr. Katarina Lindley	USA	100	5.0% (5)	87.1%	0.0% (0)	100.0%
Dr. Ben Marble	USA	150,000			0.0% (4)	99.9%
Dr. Edimilson Migowski	Brazil	2,000	0.3% (7)	99.1%	0.1% (2)	95.9%
Dr. Abdulrahman Mohana	Saudi Arabia	2,733			0.0% (0)	100.0%
Dr. Carlos Nigro	Brazil	5,000	0.9% (45)	97.7%	0.5% (23)	81.3%
Dr. Benoit Ochs	Luxembourg	800			0.0% (0)	100.0%
Dr. Ortore	Italy	240	1.2% (3)	96.8%	0.0% (0)	100.0%
Dr. Valerio Pascua one death for a patient presenting on the 5th day in need of supplemental oxygen	Honduras	415	6.3% (26)	83.8%	0.2% (1)	90.2%
Dr. Sebastian Pop	Romania	300			0.0% (0)	100.0%
Dr. Brian Proctor	USA	869	2.3% (20)	94.0%	0.2% (2)	90.6%
Dr. Anastacio Queiroz	Brazil	700			0.0% (0)	100.0%
Dr. Didier Raoult	France	8,315	2.6% (214)	93.3%	0.1% (5)	97.6%
Dr. Karin Ried up to 99yo, 73% comorbidities, av. age 63	Turkey	237			0.4% (1)	82.8%
Dr. Roman Rozencwaig patients up to 86 years old	Canada	80			0.0% (0)	100.0%
Dr. Vipul Shah	India	8,000			0.1% (5)	97.5%
Dr. Silvestre Sobrinho	Brazil	116	8.6% (10)	77.7%	0.0% (0)	100.0%
Dr. Vladimir Zelenko	USA	2,200	0.5% (12)	98.6%	0.1% (2)	96.3%
Mean improvement with early treatment protocols		235,564	HospitalizationHosp.	94.0%	MortalityDeath	94.7%

Physician results with early treatment protocols compared to no early treatment. These results are subject to selection and ascertainment bias and more accurate analysis requires details of the patient populations and followup, however results are consistently better across many teams, and consistent with the extensive controlled trial evidence that shows a significant reduction in risk with many early treatments, and improved results with the use of multiple treatments in combination.

Treatment

Improvement
(early)

Studies
(early)

82%

71%

69%

62%

62%

61%

60%

56%

47%

41%

41%

34%

26%

24%

18%

-17%

-29%

-52%

Early treatments approved by >2 countries. 101 countries have officially approved treatments. Details.

Zinc

Asoudeh	250 patients prophylaxis: 57% lower severe cases [p=0.03]
Lahaye	Sufficiency: 28% lower mortality [p=0.26] and 53% lower severe cases [p=0.02]
Schloss	Review of 22 nutritional factors that have been linked to COVID-19 outcomes, the role of nutrients in COVID-19 infection, and the prevalence of..

Bromhexine

Vila Méndez

191 patient early treatment RCT: 67% lower hospitalization [p=0.49] and 7% worse viral clearance [p=0.82]

Vitamin C

Asoudeh	250 patients prophylaxis: 69% lower severe cases [p=0.003]
Schloss	Review of 22 nutritional factors that have been linked to COVID-19 outcomes, the role of nutrients in COVID-19 infection, and the prevalence of..

Vitamin A

Lahaye

Sufficiency: 23% lower mortality [p=0.02] and 2% lower severe cases [p=0.4]

Peginterferon Lambda

Kim	14 patient late treatment RCT: 200% higher ICU admission [p=1], 25% longer hospitalization [p=0.59], and 12% improved viral clearance [p=1]

Vitamin D

Bucurica	11,182 patients sufficiency: 28% fewer cases [p<0.0001]
Montini	Case control analysis with 149 multiple sclerosis patients and 292 matched controls in Italy, showing lower risk of COVID-19 cases with higher..
Bhat	580 patients prophylaxis: 34% fewer symptomatic cases [p=0.01]
Schloss	Review of 22 nutritional factors that have been linked to COVID-19 outcomes, the role of nutrients in COVID-19 infection, and the prevalence of..
Topan	2,342 patients sufficiency: 31% lower mortality [p=0.02] and 11% lower severe cases [p=0.02]
Domazet Bugarin	152 patient ICU RCT: 21% lower mortality [p=0.2], no change in recovery [p=0.71], and 6% longer hospitalization [p=0.76]
Liu	Prospective study of 250 healthcare workers in the USA. The results are unclear - Figure 3 shows ~40% lower incidence with vitamin D supplementation..
Şengül	318 patients prophylaxis: 69% fewer cases [p=0.004]

Paxlovid

Kim	In Silico analysis of drug–drug interactions for paxlovid. From 2,248 prescription drugs, 1,628 were predicted to have 2,445 interactions with..

Molnupiravir

Goodwin

416 patients early treatment: 110% higher mortality [p=0.47] and 58% lower hospitalization [p=0.7]

Sotrovimab

Goodwin

505 patients early treatment: 75% lower mortality [p=0.55] and 60% lower hospitalization [p=0.35]

N-acetylcysteine

Schloss

Review of 22 nutritional factors that have been linked to COVID-19 outcomes, the role of nutrients in COVID-19 infection, and the prevalence of..

Alkalinization

Wang	55 patient late treatment RCT: 39% shorter hospitalization [p=0.0009]

Budesonide

Samajdar

102 patients late treatment: 69% lower hospitalization [p=0.07] and 29% improved recovery [p=0.008]

Melatonin

Langen

Extensive review of melatonin and the evidence of beneficial effects for many health issues including COVID-19.

Lactoferrin

Matino

218 patient late treatment RCT: 12% higher mortality [p=0.85], 45% higher ventilation [p=0.39], 6% higher combined mortality/ICU admission [p=0.87], and 34% worse recovery [p=0.12]

Recent studies (see the individual treatment pages for all studies):


Mar 21	Lahaye et al., Nutrients, doi:10.3390/nu15061516	Minerals and Antioxidant Micronutrients Levels and Clinical Outcome in Older Patients Hospitalized for COVID-19 during the First Wave of the Pandemic
	28% lower mortality [p=0.26] and 53% lower severe cases [p=0.02]. Retrospective 235 hospitalized COVID-19 patients in France, showing lower zinc levels associated with severe cases. Results are provided for zinc levels as a continuous value.
Mar 15	Wang et al., Frontiers in Public Health, doi:10.3389/fpubh.2023.1145669	Efficacy of nasal irrigation and oral rinse with sodium bicarbonate solution on virus clearance for COVID-19 patients
	39% shorter hospitalization [p=0.0009]. RCT 55 mild/moderate patients in China, showing shorter hospitalization with sodium bicarbonate nasal irrigation and oral rinsing. Oral rinse with 5% sodium bicarbonate solution three times daily. Nasal irrigation two times with the solut..
Mar 15	Goodwin et al., PLOS ONE, doi:10.1371/journal.pone.0281915	Evaluation of outpatient treatment for non-hospitalised patients with COVID-19: The experience of a regional centre in the UK
	110% higher mortality [p=0.47] and 58% lower hospitalization [p=0.7]. Retrospective 604 outpatients in the UK, showing lower risk of hospitalization with molnupiravir treatment, without statistical significance due to the small number of hospitalizations.
Mar 15	Schloss et al., Inflammopharmacology, doi:10.1007/s10787-023-01183-3 (Review)	Nutritional deficiencies that may predispose to long COVID
	Review of 22 nutritional factors that have been linked to COVID-19 outcomes, the role of nutrients in COVID-19 infection, and the prevalence of multiple nutritional deficiencies in the population.
Mar 13	Kim et al., Proceedings of the National Academy of Sciences, doi:10.1073/pnas.2221857120	Computational prediction of interactions between Paxlovid and prescription drugs
	In Silico analysis of drug–drug interactions for paxlovid. From 2,248 prescription drugs, 1,628 were predicted to have 2,445 interactions with nirmatrelvir and/or ritonavir (673 for nirmatrelvir and 1,403 ritonavir). For 873 drugs, author..
Mar 9	Siuka et al., F1000Research, doi:10.12688/f1000research.131730.1	The effect of Vitamin D levels on the course of COVID-19 in hospitalized patients – a 1-year prospective cohort study
	56% lower mortality [p=0.24], 59% higher ICU admission [p=0.59], and 61% higher severe cases [p=0.009]. Prospective study of 301 hospitalized patients in Slovenia, showing higher mortality with vitamin D deficiency, without statistical significance. Fewer patients with severe cases were deficient, which authors hypothesize was due to their..
Mar 6	Bucurica et al., Diagnostics, doi:10.3390/diagnostics13050998	Association of Vitamin D Deficiency and Insufficiency with Pathology in Hospitalized Patients
	28% fewer cases [p<0.0001]. Retrospective 11,182 hospitalized patients in Romania, showing vitamin D deficiency associated with COVID-19 cases.
Mar 6	Bhat et al., Journal of Infection, doi:10.1016/j.jinf.2023.03.004	Effect of calcifediol supplementation as add-on therapy on the immune repertoire in recipients of the ChAdOx1 nCoV-19 vaccine: A prospective open-label, placebo-controlled, clinical trial
	34% fewer symptomatic cases [p=0.01]. Prospective study of 580 ChAdOx1 recipients, 262 treated with calcifediol (patient choice), showing lower cases with treatment. Supplementation did not significantly affect antibody levels following ChAdOx1 receipt. Calcifediol patients w..
Mar 5	Langen, M., Rounding The Earth (Review) (Preprint)	Melatonin - the Hormone of Both Sun and Darkness - Protects Your Health and Can Save Your Life
	Extensive review of melatonin and the evidence of beneficial effects for many health issues including COVID-19.
Mar 5	Durstenfeld et al., medRxiv, doi:10.1101/2023.03.02.23286730	Association of Nirmatrelvir/Ritonavir Treatment with Long COVID Symptoms in an Online Cohort of Non-Hospitalized Individuals Experiencing Breakthrough SARS-CoV-2 Infection in the Omicron Era
	14% higher PASC [p=0.4]. Retrospective 4,684 COVID+ patients mostly in the USA, 988 treated with paxlovid, showing higher odds of long COVID with treatment, without statistical significance.
Mar 5	Liu et al., The Journal of Nutrition, doi:10.1016/j.tjnut.2023.03.001	Vitamin D and SARS-CoV-2 Infection: SERVE Study (SARS-CoV-2 Exposure and the Role of Vitamin D among Hospital Employees)
	Prospective study of 250 healthcare workers in the USA. The results are unclear - Figure 3 shows ~40% lower incidence with vitamin D supplementation, while the text indicates OR 1.18. Authors collected symptom information, stating that &q..
Mar 4	Matino et al., Nutrients, doi:10.3390/nu15051285	Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial
	12% higher mortality [p=0.85], 45% higher ventilation [p=0.39], 6% higher combined mortality/ICU admission [p=0.87], and 34% worse recovery [p=0.12]. RCT 218 hospitalized patients in Italy, showing no significant differences with lactoferrin treatment. Authors note that in several previous studies showing clinical improvement, lactoferrin was given at an earlier stage of disease. Autho..
Mar 4	Ibrahim Alhajjaji et al., Saudi Pharmaceutical Journal, doi:10.1016/j.jsps.2023.02.011	Effect of zinc supplementation on symptom reduction and length of hospital stay among pediatric patients with Coronavirus Disease 2019 (COVID-19)
	88% lower mortality [p=0.13], 26% lower ventilation [p=0.75], 3% lower ICU admission [p=1], and 73% lower progression [p=0.004]. Retrospective 101 hospitalized pediatric patients in Saudi Arabia, showing zinc treatment associated with lower respiratory failure and shorter hospitalization in unadjusted results. Patients receiving zinc were older. Authors note elevat..
Mar 3	Al-Gharrawi et al., Scientific Reports, doi:10.1038/s41598-023-30859-7	Association of ApaI rs7975232 and BsmI rs1544410 in clinical outcomes of COVID-19 patients according to different SARS-CoV-2 variants
	Retrospective 3,184 patients in Iran, showing COVID-19 outcomes for specific variants were associated with genotypes of the ApaI rs7975232 and BsmI rs1544410 vitamin D receptor polymorphisms.
Mar 3	Samajdar et al., Lung India, doi:10.4103/lungindia.lungindia_268_22	Effectiveness of budesonide formoterol fixed-dose combination MDI in reducing cough symptoms in COVID-19 patients: A real-world evidence study
	69% lower hospitalization [p=0.07] and 29% improved recovery [p=0.008]. Prospective study of 102 patients in India, showing improved recovery of cough with budesonide+formoterol. Authors note better results with earlier treatment. Budesonide 800mcg + formoterol 12mcg bid for 7 days.
Mar 3	Kirenga et al., Molecular Psychiatry, doi:10.1038/s41380-023-02004-3	Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study
	68% lower mortality [p<0.0001] and 53% improved recovery [p=0.04]. Prospective study of 316 hospitalized patients in Uganda, 94 receiving fluvoxamine, showing significantly lower mortality and improved recovery with treatment.
Mar 2	Cousins et al., medRxiv, doi:10.1101/2023.02.28.23286515	Association between spironolactone use and COVID-19 outcomes in population-scale claims data: a retrospective cohort study
	18% lower mortality [p=0.004] and 17% lower ventilation [p<0.0001]. PSM retrospective 898,303 hospitalized COVID-19 patients in the USA, 16,324 on spironolactone, showing lower mortality and ventilation with spironolactone use.
Mar 2	Spivak et al., Microbiology Spectrum, doi:10.1128/spectrum.04674-22	A Randomized Clinical Trial Testing Hydroxychloroquine for Reduction of SARS-CoV-2 Viral Shedding and Hospitalization in Early Outpatient COVID-19 Infection
	73% higher hospitalization [p=0.54], 20% improved recovery [p=0.19], and 17% improved viral clearance [p=0.19]. Delayed publication of an early terminated late treatment RCT with low-risk (no mortality) outpatients in the USA, showing no significant differences with HCQ. Authors do not provide symptom onset data, but the subgroup analysis suggests ..
Mar 1	Irie, K., Yakugaku Zasshi, doi:10.1248/yakushi.22-00169-1 (Dosing)	Pharmacokinetic Study of Antiviral Drugs in Patients with COVID-19
	Pharmacokinetics study measuring the blood concentration of favipiravir in 7 critical patients in Japan, showing concentrations below the EC₅₀ in 33 of 36 samples when using the standard dosing regimen. Authors note that patient character..
Feb 28	Punzalan et al., Frontiers in Immunology, doi:10.3389/fimmu.2023.1123497	Utility of laboratory and immune biomarkers in predicting disease progression and mortality among patients with moderate to severe COVID-19 disease at a Philippine tertiary hospital
	42% higher mortality [p=0.12] and 59% higher progression [p=0.001]. Prospective study of 400 hospitalized patients in the Philippines, showing higher progression with remdesivir in unadjusted results, without statistical significance.
Feb 28	Topan et al., Nutrients, doi:10.3390/nu15051227	25 Hydroxyvitamin D Serum Concentration and COVID-19 Severity and Outcome—A Retrospective Survey in a Romanian Hospital
	31% lower mortality [p=0.02] and 11% lower severe cases [p=0.02]. Retrospective 2,342 hospitalized COVID-19 patients in Romania with vitamin D levels measured on admission day, showing lower risk of mortality and severe/critical cases with vitamin D levels ≥ 20ng/mL.
Feb 28	Domazet Bugarin et al., Nutrients, doi:10.3390/nu15051234	Vitamin D Supplementation and Clinical Outcomes in Severe COVID-19 Patients—Randomized Controlled Trial
	21% lower mortality [p=0.2], no change in recovery [p=0.71], and 6% longer hospitalization [p=0.76]. Very late stage RCT 155 ICU patients in Croatia with low vitamin D levels, showing no significant differences with 10,000IU cholecalciferol daily. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more succe..
Feb 28	Mathew et al., Rheumatology Advances in Practice, doi:10.1093/rap/rkad025	Predictors of COVID-19 severity and outcomes in Indian patients with rheumatic diseases: a prospective cohort study
	20% lower mortality [p=0.8], no change in hospitalization [p=0.94], and 40% lower severe cases [p=0.37]. Prospective study of 64 rheumatic disease patients with COVID-19, showing no significant difference in outcomes with HCQ use.
Feb 28	Llanos-Cuentas et al., BMC Research Notes, doi:10.1186/s13104-023-06281-7	Hydroxychloroquine to prevent SARS-CoV-2 infection among healthcare workers: early termination of a phase 3, randomised, open-label, controlled clinical trial
	69% more cases [p=0.46]. Early terminated healthcare worker PrEP RCT with only 68 patients and 8 cases, showing no significant difference with HCQ. No information on symptoms per group, case severity, or the timing of cases is provided.
Feb 28	Chen et al., Infection and Drug Resistance, doi:10.2147/idr.s400561	Plasma 25(OH)D Level is Associated with the Nucleic Acid Negative Conversion Time of COVID-19 Patients: An Exploratory Study
	40% improved viral clearance [p=0.01]. Retrospective 158 COVID+ patients in China, showing low vitamin D levels associated with slower viral clearance.
Feb 27	Bader et al., Nutrients, doi:10.3390/nu15051188	The Effect of Weekly 50,000 IU Vitamin D3 Supplements on the Serum Levels of Selected Cytokines Involved in Cytokine Storm: A Randomized Clinical Trial in Adults with Vitamin D Deficiency
	RCT 100 patients in Jordan, showing that high-dose cholecalciferol (50,000 IU/week) significantly increased IL-6, indicating that high weekly doses could have a negative effect for cytokine storm with COVID-19. Other studies have found no..
Feb 27	Chavda et al., Pharmacological Reports, doi:10.1007/s43440-023-00463-7 (Review)	Nasal sprays for treating COVID-19: a scientific note
	Review of nasal sprays for treatment of COVID-19. Authors note that the nasal epithelium is typically the primary site of SARS-CoV-2 infection, and there may be significant advantages for treatments via the nasal route.
Feb 27	Tan et al., Journal of the ASEAN Federation of Endocrine Societies, doi:10.15605/jafes.038.01.07	Association of Vitamin D levels on the Clinical Outcomes of Patients Hospitalized for COVID-19 in a Tertiary Hospital
	71% lower progression [p=0.04], 91% lower mortality [p=0.002], and 82% lower ICU admission [p=0.01]. Retrospective 135 hospitalized COVID-19 patients in the Philippines, showing higher risk of a poor outcome with vitamin D deficiency.
Feb 27	Wang et al., The Lancet Regional Health - Western Pacific, doi:10.1016/j.lanwpc.2023.100716 (meta analysis)	Relationship between antidepressants and severity of SARS-CoV-2 Omicron infection: a retrospective cohort study using real-world data
	PSM retrospective 60,903 hospitalized COVID-19 patients in Hong Kong, showing antidepressants associated with lower mortality, including for SSRIs, and for FIASMA antidepressants.
Feb 24	Kim et al., Frontiers in Medicine, doi:10.3389/fmed.2023.1095828	Peginterferon lambda for the treatment of hospitalized patients with mild COVID-19: A pilot phase 2 randomized placebo-controlled trial
	200% higher ICU admission [p=1], 25% longer hospitalization [p=0.59], and 12% improved viral clearance [p=1]. Very small RCT with 14 hospitalized patients in the USA showing no significant differences with peginterferon lambda. Viral load was improved, however 86% of treatment versus 14% of control patients received remdesivir, and the median bas..
Feb 24	European Medicines Agency (News)	Refusal of the marketing authorisation for Lagevrio (molnupiravir)
	The European Medicines Agency has recommended the refusal of the marketing authorisation of molnupiravir.
Feb 24	Shah et al., BMJ Open, doi:10.1136/bmjopen-2022-067910	Colchicine and high-intensity rosuvastatin in the treatment of non-critically ill patients hospitalised with COVID-19: a randomised clinical trial
	75% higher mortality [p=0.54], 200% higher ventilation [p=0.28], and 46% higher severe cases [p=0.34]. RCT 250 late stage (80% on oxygen) hospitalized patients in the USA, showing no significant differences with combined colchicine/rosuvastatin treatment. There was a trend towards increased risk, which authors note may be due to chance bec..
Feb 23	Ma et al., PLOS ONE, doi:10.1371/journal.pone.0282210	Is metformin use associated with low mortality in patients with type 2 diabetes mellitus hospitalized for COVID-19? a multivariable and propensity score-adjusted meta-analysis
	Meta analysis of 22 metformin studies, showing significantly lower mortality with metformin use prior to hospitalization.
Feb 22	Wan et al., Journal of Infection, doi:10.1016/j.jinf.2023.02.029	Molnupiravir and nirmatrelvir-ritonavir reduce mortality risk during post-acute COVID-19 phase
	11% lower mortality [p=0.02], 1% lower hospitalization [p=0.76], and 4% higher progression [p=0.18]. Retrospective 30,040 hospitalized patients in Hong Kong, showing lower mortality with molnupiravir treatment.
Feb 21	Mitsushima et al., International Journal of General Medicine, doi:10.2147/IJGM.S394413	Risk of Underlying Diseases and Effectiveness of Drugs on COVID-19 Inpatients Assessed Using Medical Claims in Japan: Retrospective Observational Study
	44% higher mortality [p=0.01]. Retrospective 18,566 hospitalized patients in Japan, showing higher mortality with remdesivir treatment.
Feb 21	Kim et al., International Journal of Environmental Research and Public Health, doi:10.3390/ijerph20053832	Serious Clinical Outcomes of COVID-19 Related to Acetaminophen or NSAIDs from a Nationwide Population-Based Cohort Study
	71% higher mortality [p=0.34], 14% higher ventilation [p=1], 40% lower ICU admission [p=0.72], and 9% higher need for oxygen therapy [p=0.87]. PSM retrospective in South Korea, showing no significant differences in outcomes with acetaminophen use vs. NSAID use. Adherence and dosage are unknown.
Feb 21	Merck, Press Release (Preprint)	Merck Provides Update on Phase 3 MOVe-AHEAD Trial Evaluating LAGEVRIO™ (molnupiravir) for Post-exposure Prophylaxis for Prevention of COVID-19
	MOVe-AHEAD PEP RCT reporting no significant difference in cases. Limited information is available. There were 23.6% fewer cases with treatment, but the number of cases and confidence interval are not provided.
Feb 20	Miraz et al., International Journal of Clinical Practice, doi:10.1155/2023/9917306	Nigelladine A among Selected Compounds from Nigella sativa Exhibits Propitious Interaction with Omicron Variant of SARS-CoV-2: An In Silico Study
	In Silico study of 96 phytochemical compounds of nigella sativa, identifying Nigelladine A as the most promising compound for SARS-CoV-2 inhibition with the highest docking scores for the spike protein and M^pro. Dithymoquinone, kaempferol..
Feb 20	Naggie et al., JAMA, doi:10.1001/jama.2023.1650	Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial
	600µg/kg arm of ACTIV-6. Results of this trial are unreliable, with multiple critical anomalies, and no response from the authors. For details see [c19early].
Feb 20	Delgado et al., Research Square, doi:10.21203/rs.3.rs-2596201/v1 (Preprint)	Investigational medications in 9,638 hospitalized patients with severe COVID-19: lessons from the “fail-and-learn” strategy during the first two waves of the pandemic in 2020
	26% lower mortality [p=0.002]. PSM retrospective 9,638 patients in the USA, showing significantly lower mortality with HCQ in early 2020 (1,157 HCQ patients), and no significant difference in late 2020 (82 HCQ patients). The few patients treated in the later period may..

We aim to cover the most promising early treatments for COVID-19. We use pre-specified effect extraction criteria that prioritizes more serious outcomes, for details see methods. For specific outcomes and different treatment stages see the individual pages. Not all treatments are covered here, effectiveness has been reported for many other treatments in studies. Of the 2,617 studies, 1,703 present results comparing with a control group, 1,550 are treatment studies, and 153 analyze outcomes based on serum levels. There are 31 animal studies, 63 in silico studies, 133 in vitro studies, and 131 meta analyses.

Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. 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. FLCCC and WCH provide treatment protocols.

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