COVID-19 early treatment: real-time analysis of

1,162 studies
Analysis of 30 COVID-19 early treatments, and database of
231 other potential treatments.
67
countries have approved early treatments.
Treatments do not replace vaccines and other
measures. All practical,
effective, and safe means should be used. Elimination is a race against
viral
evolution. No treatment, vaccine, or intervention is 100% available and
effective for all
variants. Denying efficacy increases the risk of COVID-19
becoming endemic; and increases
mortality, morbidity, and collateral
damage.
All studies combined (pooled effects, all stages) c19early.com Dec 1, 2021

Improvement, RR [CI] Studies Patients Cost

Paxlovid 95% 0.05 [0.00-0.81] 1 1,219 $700 very few trials/events
Proxalutamide 84% 0.16 [0.12-0.22] 3 1,090 n/a few trials/events
Iota-carragee.. 80% 0.20 [0.04-0.89] 1 394 $1 very few trials/events
Casirivimab/i.. 74% 0.26 [0.12-0.57] 9 35,238 $2,100 intravenous/subcutaneous
Nigella Sativa 67% 0.33 [0.21-0.52] 4 1,291 $5 few trials/events
Ivermectin 67% 0.33 [0.27-0.42] 67 49,516 $1
Sotrovimab 67% 0.33 [0.01-8.16] 1 583 $2,100 intravenous
Bamlanivimab 65% 0.35 [0.19-0.64] 9 19,400 $1,250 high variant dependence
Melatonin 64% 0.36 [0.22-0.58] 11 13,517 $1
Povidone-Iod.. 60% 0.40 [0.25-0.65] 9 2,256 $1
Curcumin 59% 0.41 [0.24-0.70] 9 867 $5 few trials/events
Antiandrogens 59% 0.41 [0.17-0.99] 6 523 $5
Quercetin 56% 0.44 [0.17-1.13] 5 936 $5 few trials/events
Vitamin A 55% 0.45 [0.20-1.02] 5 15,863 $2 few trials/events
Molnupiravir 55% 0.45 [0.24-0.85] 5 2,724 $700
Nitazoxanide 55% 0.45 [0.15-1.35] 6 1,464 $4
Zinc 48% 0.52 [0.41-0.66] 20 50,281 $1
Vitamin D 45% 0.55 [0.47-0.63] 53 66,371 $1
Budesonide 45% 0.55 [0.31-0.98] 3 8,751 $4 few trials/events
Bromhexine 45% 0.55 [0.40-0.77] 5 291 $5 few trials/events
Fluvoxamine 38% 0.62 [0.42-0.93] 5 2,052 $4
Favipiravir 34% 0.66 [0.52-0.85] 18 4,288 $20
Colchicine 31% 0.69 [0.54-0.88] 12 17,762 $1
Hydroxychloro.. 25% 0.75 [0.70-0.79] 298 413,756 $1
Probiotics 21% 0.79 [0.69-0.91] 13 16,948 $5
Aspirin 20% 0.80 [0.70-0.92] 23 80,752 $1
Remdesivir 19% 0.81 [0.73-0.89] 24 97,505 $3,120
Metformin 14% 0.86 [0.78-0.96] 11 25,758 $10
Vitamin C 13% 0.87 [0.77-0.99] 26 30,635 $1
Conv. Plasma -1% 1.01 [0.90-1.13] 13 14,426 $5,000 intravenous
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+

Favors treatment Favors control

Random effects meta-analysis of

all studies combined (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.

Early treatment studies (pooled effects) c19early.com Dec 1, 2021

Improvement, RR [CI] Studies Patients Cost
Paxlovid 95% 0.05 [0.00-0.81] 1 1,219 $700 very few trials/events
Fluvoxamine 89% 0.11 [0.01-0.85] 2 277 $4 very few trials/events
Nigella Sativa 84% 0.16 [0.05-0.48] 3 915 $5 few trials/events
Budesonide 82% 0.18 [0.04-0.79] 1 146 $4 very few trials/events
Vitamin D 81% 0.19 [0.10-0.35] 6 912 $1 few trials/events
Bromhexine 79% 0.21 [0.06-0.72] 2 96 $5 very few trials/events
Vitamin A 79% 0.21 [0.07-0.61] 2 240 $2 very few trials/events
Quercetin 79% 0.21 [0.02-1.82] 2 194 $5 very few trials/events
Bamlanivimab 79% 0.21 [0.11-0.41] 6 17,653 $1,250 high variant dependence
Melatonin 78% 0.22 [0.06-0.75] 2 91 $1 very few trials/events
Zinc 74% 0.26 [0.03-2.33] 3 982 $1 very few trials/events
Proxalutamide 73% 0.27 [0.03-2.39] 2 445 n/a very few trials/events
Curcumin 71% 0.29 [0.11-0.74] 6 707 $5 few trials/events
Povidone-Iod.. 71% 0.29 [0.16-0.54] 7 878 $1 few trials/events
Antiandrogens 68% 0.32 [0.17-0.59] 2 357 $5 very few trials/events
Casirivimab/i.. 68% 0.32 [0.16-0.67] 5 22,392 $2,100 intravenous/subcutaneous
Ivermectin 67% 0.33 [0.24-0.47] 29 27,658 $1
Sotrovimab 67% 0.33 [0.01-8.16] 1 583 $2,100 intravenous
Hydroxychloro.. 64% 0.36 [0.28-0.46] 33 54,693 $1
Molnupiravir 55% 0.45 [0.24-0.85] 5 2,724 $700
Favipiravir 51% 0.49 [0.31-0.78] 4 467 $20 very few trials/events
Nitazoxanide 49% 0.51 [0.13-1.95] 5 1,414 $4 few trials/events
Vitamin C 43% 0.57 [0.27-1.23] 3 445 $1 few trials/events
Probiotics 34% 0.66 [0.55-0.80] 2 323 $5 few trials/events
Metformin -15%1.15 [0.73-1.83] 1 423 $10 very few trials/events
Conv. Plasma -93%1.93 [0.47-7.87] 3 716 $5,000 intravenous
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+

Favors treatment Favors control

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.

All mortality results (all stages) c19early.com Dec 1, 2021

Improvement, RR [CI] Studies Patients Cost
Paxlovid 95% 0.05 [0.00-0.81] 1 1,219 $700 very few trials/events
Antiandrogens 95% 0.05 [0.00-2062] 1 118 $5 very few trials/events
Povidone-Iod.. 88% 0.12 [0.03-0.50] 1 606 $1 very few trials/events
Nigella Sativa 87% 0.13 [0.04-0.49] 2 732 $5 few trials/events
Bromhexine 87% 0.13 [0.01-1.23] 2 178 $5 very few trials/events
Molnupiravir 86% 0.14 [0.02-0.78] 2 1,610 $700 very few trials/events
Proxalutamide 84% 0.16 [0.12-0.22] 3 1,090 n/a few trials/events
Melatonin 79% 0.21 [0.08-0.56] 4 1,650 $1
Bamlanivimab 71% 0.29 [0.08-1.01] 6 17,830 $1,250 high variant dependence
Curcumin 70% 0.30 [0.14-0.64] 4 434 $5
Casirivimab/i.. 68% 0.32 [0.08-1.30] 4 29,298 $2,100 intravenous/subcutaneous
Sotrovimab 67% 0.33 [0.01-8.16] 1 583 $2,100 intravenous
Nitazoxanide 60% 0.40 [0.10-1.58] 3 923 $4 very few trials/events
Probiotics 59% 0.41 [0.23-0.72] 4 539 $5 few trials/events
Ivermectin 58% 0.42 [0.31-0.57] 28 36,773 $1
Vitamin D 50% 0.50 [0.38-0.66] 31 12,599 $1
Quercetin 46% 0.54 [0.12-2.40] 3 623 $5 very few trials/events
Vitamin A 42% 0.58 [0.07-4.59] 2 207 $2 few trials/events
Colchicine 40% 0.60 [0.42-0.86] 10 17,373 $1
Budesonide 39% 0.61 [0.22-1.67] 1 1,586 $4 very few trials/events
Zinc 39% 0.61 [0.49-0.78] 10 10,416 $1
Fluvoxamine 36% 0.64 [0.47-0.86] 3 1,775 $4 few trials/events
Hydroxychloro.. 22% 0.78 [0.73-0.83] 184 291,871 $1
Vitamin C 20% 0.80 [0.66-0.98] 17 14,205 $1
Remdesivir 19% 0.81 [0.73-0.89] 23 97,363 $3,120
Metformin 19% 0.81 [0.73-0.90] 8 7,303 $10
Aspirin 17% 0.83 [0.71-0.96] 20 70,208 $1
Conv. Plasma -1% 1.01 [0.90-1.13] 13 14,426 $5,000 intravenous
Favipiravir -8% 1.08 [0.73-1.59] 7 2,998 $20
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+

Favors treatment Favors control

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.

Early treatment mortality results c19early.com Dec 1, 2021

Improvement, RR [CI] Studies Patients Cost
Paxlovid 95% 0.05 [0.00-0.81] 1 1,219 $700 very few trials/events
Bromhexine 91% 0.09 [0.01-1.59] 1 78 $5 very few trials/events
Povidone-Iod.. 88% 0.12 [0.03-0.50] 1 606 $1 very few trials/events
Nigella Sativa 87% 0.13 [0.04-0.49] 2 732 $5 few trials/events
Molnupiravir 86% 0.14 [0.02-0.78] 2 1,610 $700 very few trials/events
Bamlanivimab 86% 0.14 [0.04-0.50] 4 17,048 $1,250 high variant dependence
Vitamin A 86% 0.14 [0.03-0.61] 1 140 $2 very few trials/events
Casirivimab/i.. 84% 0.16 [0.03-0.95] 3 19,513 $2,100 intravenous/subcutaneous
Curcumin 84% 0.16 [0.04-0.61] 2 314 $5 few trials/events
Zinc 79% 0.21 [0.03-1.47] 1 518 $1 very few trials/events
Quercetin 79% 0.21 [0.02-1.82] 2 194 $5 very few trials/events
Vitamin D 79% 0.21 [0.12-0.39] 4 514 $1 few trials/events
Hydroxychloro.. 75% 0.25 [0.16-0.40] 13 50,628 $1
Proxalutamide 73% 0.27 [0.03-2.39] 2 445 n/a very few trials/events
Sotrovimab 67% 0.33 [0.01-8.16] 1 583 $2,100 intravenous
Ivermectin 52% 0.48 [0.32-0.72] 10 25,482 $1
Nitazoxanide 41% 0.59 [0.02-13.8] 2 873 $4 very few trials/events
Conv. Plasma -93%1.93 [0.47-7.87] 3 716 $5,000 intravenous
Vitamin C -204%
3.04 [0.13-72.9] 1 98 $1 very few trials/events
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+

Favors treatment Favors control

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.
m
United Kingdo
Improvement

Bangladesh

Philippines
Treatment

DR Congo
Indonesia

Germany
Pakistan

Thailand
Vietnam
Ethiopia
Mexico
Nigeria

France
Russia

Turkey
Studies

Japan
China

Egypt
Brazil
  (early)

  (early)

India
USA

Iran
 Budesonide 82% 1                                            

Casirivimab/im.. 68% 5                                            

Ivermectin 67% 29                                            

Sotrovimab 67% 1                                            

Hydroxychloro.. 64% 33                                            

Favipiravir 51% 4                                            

Remdesivir - 0                                            

Early treatments approved by >2 countries. 67 countries have officially approved treatments.
Details.

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

Early Merck News R… death, ↓89.0%, p=0.0 Merck and Ridgeback Biotherapeutics Provide…
26
Nov

Details  
News release reporting results of the MOVe-OUT trial, showing significantly lower risk of hos…

Early Ried et al., Cure… no recov., ↓30.6%, p= Therapies to Prevent Progression of COVID-1…
25
Nov

Details  
RCT 237 patients in Turkey, 162 treated with IV vitamin C in addition to HCQ/AZ/zinc/vitami…

Levels Jenei et al., Clinical Nutrition ESPEN, d… COVID-19 mortality is associated with low Vit…
24
Nov

Details  
Retrospective 257 hospitalized patients in Hungary, showing mortality associated with lowe…

Early Holubar et al., … hosp., ↓89.0%, p=0.0 Favipiravir for treatment of outpatients with a…
24
Nov

Details  
Small RCT 116 mITT patients in the USA, 59 treated with favipiravir, showing no significant d…

Late Ozer et al., Jou… death, ↓75.0%, p=0.0 Effectiveness and Safety of Ivermectin in COV…
23
Nov

Details  
Small prospective PSM study in the USA, showing 75% lower mortality with ivermectin treat…

In Vit… Tandel et al., bi… in vitro Metformin Suppresses SARS-CoV-2 in Cell Cu…
19
Nov

Details  
In Vitro study showing metformin inhibits SARS-CoV-2 in Caco2 cells. Metformin reduced vir…

Late Chuah et al., Cli… death, ↑1154.0%, p=0 Efficacy of Early Treatment with Favipiravir on…
19
Nov

Details  
RCT 500 hospitalized patients in Malaysia, showing no significant differences with favipiravi…

Late RECOVERY Col… death, ↓4.0%, p=0.35 Aspirin in patients admitted to hospital with C…
18
Nov

Details  
RCT 14,892 late stage patients, 7,351 treated with aspirin, showing slightly improved dischar…

PrEP Samajdar et al.,… cases, ↓74.5%, p<0.0 Ivermectin and Hydroxychloroquine for Chem…
16 ov 17

Details  
Physician survey in India with 164 ivermectin prophylaxis, 129 HCQ prophylaxis, and 81 cont…
Nov N

In Vit… Marín-Palma et… in vitro Curcumin Inhibits In Vitro SARS-CoV-2 Infecti…

Details  
In Vitro study showing antiviral and anti-inflammatory effects of curcumin during SARS-CoV-…
 PrEP Isa et al., medR… symp. case, ↓92.6%, Repeat Subcutaneous Administration of REG…
16
Nov

Details  
RCT 969 patients, 729 treated with monthly subcutaneous casirivimab/imdevimab, showing…

PrEP Oskotsky et al.,… death, ↑57.9%, p=0.6 Mortality Risk Among Patients With COVID-19…
15
Nov

Details  
Retrospective database analysis of 83,584 patients in the USA, showing lower mortality with…

In Vit… Bahun et al., Fo… in vitro Inhibition of the SARS-CoV-2 3CLpro main pro…
14
Nov

Details  
In Silico and In Vitro study of plant polyphenols identifying quercetin, curcumin, ellagic acid, …

Levels Sacristán et al., Transplantation Procee… Risk of severe COVID-19 infection in kidney tr…
12
Nov

Details  
Retrospective 63 COVID+ kidney transplant recipients, showing significantly lower vitamin D …

Levels Gönen et al., N… death, ↓65.8%, p=0.6 Rapid and Effective Vitamin D Supplementatio…
12
Nov

Details  
Retrospective 867 hospitalized COVID-19 patients in Turkey, showing worse outcomes with …

Levels Asghar et al., A… death, ↓53.1%, p=0.0 Evaluation of Vitamin-D Status and Its Associ…
10
Nov

Details  
Retrospective 91 hospitalized patients in Pakistan, showing vitamin D deficiency associated …

Late Shenoy et al., … death, ↑29.5%, p=0.5 Favipiravir In Adults with Moderate to Severe …
9
Nov

Details  
Late stage RCT with 353 hospitalized patients, showing no significant differences with favipi…

Late Stone et al., Research Square, doi:10.2… Rapid increase of SpO2 on room air for 34 sev…
9
Nov

Details  
Retrospective severe COVID-19 patients in Zimbabwe treated with ivermectin, doxycycline, a…

Late Tehrani et al., U… death, ↓87.1%, p=0.1 An investigation into the Effects of Intravenou…
8
Nov

Details  
RCT 54 late stage patients, 18 treated with IV vitamin C (2g every 6h for 5 days), showing si…

PEP Regeneron Pre… hosp., ↓92.3%, p=0.0 New phase 3 analyses show that a single dos…
8
Nov

Details  
Long-term results for PEP RCT NCT04452318, with 841 baseline seronegative casirivimab/i…

Revie… Goldstein, L., Tr… news Molnupiravir: mutagenic, carcinogenic, authori…

6
Nov

Details  
Discussion of concerns with molnupiravir and the MOVe-OUT trial. Author notes that results …

Early Chechter et al., … hosp., ↓94.7%, p=0.0 Evaluation of patients treated by telemedicine…
5
Nov

Details  
Prospective study of 187 telemedicine patients in Brazil. 74 presenting with moderate sympt…

Animal Abdelnabi et al… animal study The oral protease inhibitor (PF-07321332) pro…
5
Nov

Details  
In Vitro and hamster study showing paxlovid component PF-07321332 effective against fou…
5
Nov

Early Pfizer Press Re… death, ↓95.2%, p=0.0 Pfizer's novel COVID-19 oral antiviral treatmen…
Details  
Interim analysis of EPIC-HR, 607 higher risk patients treated with paxlovid (PF-07321332 + ri…
 Early Rubin et al., Op… death, ↓97.0%, p<0.0 Bamlanivimab efficacy in older and high BMI …
3
Nov

Details  
Retrospective database analysis of 1257 PCR+ outpatients with age ≥65, BMI≥35, 191 recei…

Levels Gallelli et al., Nutrients, doi:10.3390/nu… Vitamin D Serum Levels in Subjects Tested fo…
3
Nov

Details  
Analysis of 117 patients in Italy, showing COVID-19 patients had significantly lower vitamin …

Late Malaysia Minis… death, ↓69.1%, p=0.0 Kenyataan Akhbar KPK 3 November 2021 – H…
3
Nov

Details  
RCT 490 hospitalized patients in Malaysia, showing no significant differences. There was on…

Levels Atanasovska e… death, ↓40.7%, p=0.6 Vitamin D levels and oxidative stress markers …
2
Nov

Details  
Retrospective 33 COVID-19 hospitalized patients in North Macedonia, showing significantly l…

Late Sarhan et al., J… death, ↓25.7%, p=0.3 Efficacy of the early treatment with tocilizuma…
2
Nov

Details  
Small 108 patient RCT comparing HCQ vs. remdesivir in very late stage treatment. All patien…

N/A Kaleta et al., Research Square, doi:10.2… Antibody escape and global spread of SARS-C…
2
Nov

Details  
Anaysis of antibody escape showing variant A.27 completely escaped neutralization with LY…

Late Calusic et al., B… death, ↓42.0%, p=0.0 Safety and efficacy of fluvoxamine in COVID-1…
1
Nov

Details  
Prospective PSM study of 51 COVID-19 ICU patients in Croatia and 51 matched controls, sh…

Late Zarabanda et a… no recov., ↑26.9%, p= The Effect of Povidone-Iodine Nasal Spray on …

1
Nov

Details  
Very late treatment (7 days from onset) RCT comparing 11 & 13 PVP-I (0.5% and 2%), and 1…

Late Damayanti et a… no recov., ↓54.5%, p= The Effectiveness and Safety of Favipiravir in …

1
Nov

Details  
Retrospective 192 hospitalized patients in Indonesia, 96 patients treated with favipiravir, sho…

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
1,162 studies,
773 present results comparing with a control group,
684 are treatment studies,
and
89 analyze outcomes based on serum levels. There are
17 animal studies,
40 in silico
studies,
57 in vitro studies,
and 58 meta analyses.