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Levels |
Ramirez-Sandoval et al., Archives of Medical Research, doi:10.1016/j.arcmed.2021.09.006 (Peer Reviewed) |
death, ↓31.5%, p<0.0001 |
Very Low Vitamin D Levels are a Strong Independent Predictor of Mortality in Hospitalized Patients with Severe COVID-19 |
| Details Retrospective 2,908 hospitalized patients in Mexico with vitamin D levels measured on admission, showing significantly lower mortality for patients without vitamin D deficiency. |
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Details Source PDF |
| Ramirez-Sandoval et al., Archives of Medical Research, doi:10.1016/j.arcmed.2021.09.006 (Peer Reviewed) |
| Very Low Vitamin D Levels are a Strong Independent Predictor of Mortality in Hospitalized Patients with Severe COVID-19 |
Retrospective 2,908 hospitalized patients in Mexico with vitamin D levels measured on admission, showing significantly lower mortality for patients without vitamin D deficiency. ![]()
risk of death, 31.5% lower, RR 0.68, p < 0.001, high D levels 2337, low D levels 571, adjusted, >12.5ng/mL, 30 day in-hospital mortality.
hospitalization time, 22.2% lower, relative time 0.78, p < 0.001, high D levels 2337, low D levels 571.
Ramirez-Sandoval et al., 10/15/2021, retrospective, Mexico, North America, peer-reviewed, 7 authors. |
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In Vitro |
Jitaboam et al., Research Square, doi:10.21203/rs.3.rs-941811/v1 (Peer Reviewed) (In Vitro) |
in vitro |
Favipiravir and Ivermectin Showed in Vitro Synergistic Antiviral Activity against SARS-CoV-2 |
| Details In Vitro study showing a strong synergistic effect of ivermectin and favipiravir. Combining multiple antiviral drugs with different mechanisms of action helps to minimize drug resistance and toxicity. |
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Details Source PDF |
| Jitaboam et al., Research Square, doi:10.21203/rs.3.rs-941811/v1 (Peer Reviewed) (In Vitro) |
| Favipiravir and Ivermectin Showed in Vitro Synergistic Antiviral Activity against SARS-CoV-2 |
In Vitro study showing a strong synergistic effect of ivermectin and favipiravir. Combining multiple antiviral drugs with different mechanisms of action helps to minimize drug resistance and toxicity. ![]() Jitaboam et al., 10/14/2021, peer-reviewed, 8 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo. |
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Late |
Maghbooli et al., Endocrine Practice, doi:10.1016/j.eprac.2021.09.016 (Peer Reviewed) |
death, ↓40.0%, p=0.72 |
Treatment with 25-hydroxyvitamin D3 (calcifediol) is associated with a reduction in the blood neutrophil-to-lymphocyte ratio marker of disease severity in patients hospitalized with COVID-19: a pilot, multicenter, randomized, placebo-controlled double blind clinical trial |
| Details RCT 106 hospitalized patients with vitamin D levels <30ng/ml in Iran, 53 treated with calcifediol, showing that treatment was able to correct vitamin D deficiency/insufficiency, resulting in improved immune system function. Hospitalizatio.. |
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Details Source PDF |
| Maghbooli et al., Endocrine Practice, doi:10.1016/j.eprac.2021.09.016 (Peer Reviewed) |
| Treatment with 25-hydroxyvitamin D3 (calcifediol) is associated with a reduction in the blood neutrophil-to-lymphocyte ratio marker of disease severity in patients hospitalized with COVID-19: a pilot, multicenter, randomized, placebo-controlled double blind clinical trial |
RCT 106 hospitalized patients with vitamin D levels <30ng/ml in Iran, 53 treated with calcifediol, showing that treatment was able to correct vitamin D deficiency/insufficiency, resulting in improved immune system function. Hospitalization, ICU duration, ventilation, and mortality was lower with treatment, without reaching statistical significance with the small sample size. The dosage used in this trial was much lower than other trials. ![]()
risk of death, 40.0% lower, RR 0.60, p = 0.72, treatment 3 of 53 (5.7%), control 5 of 53 (9.4%).
risk of mechanical ventilation, 60.0% lower, RR 0.40, p = 0.44, treatment 2 of 53 (3.8%), control 5 of 53 (9.4%).
risk of ICU admission, 40.0% lower, RR 0.60, p = 0.42, treatment 6 of 53 (11.3%), control 10 of 53 (18.9%).
ICU time, 36.4% lower, relative time 0.64, p = 0.20, treatment 53, control 53.
hospitalization time, 16.7% lower, relative time 0.83, p = 0.10, treatment 53, control 53.
Maghbooli et al., 10/13/2021, Double Blind Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 12 authors, dosage calcifediol 25.0μg daily, mean daily dose. |
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Late |
Ivashkin et al., Probiotics Antimicrob Proteins, doi:10.1007/s12602-021-09858-5 (Peer Reviewed) |
death, ↑2.0%, p=1.00 |
Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial |
| Details RCT 200 patients, 99 treated with a probiotic (Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301). There was no sign.. |
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Details Source PDF |
| Ivashkin et al., Probiotics Antimicrob Proteins, doi:10.1007/s12602-021-09858-5 (Peer Reviewed) |
| Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial |
RCT 200 patients, 99 treated with a probiotic (Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301). There was no significant difference in mortality or recovery time, however benefits were seen for diarrhea. NCT04854941. ![]()
risk of death, 2.0% higher, RR 1.02, p = 1.00, treatment 4 of 99 (4.0%), control 4 of 101 (4.0%).
risk of mechanical ventilation, 18.4% lower, RR 0.82, p = 1.00, treatment 4 of 99 (4.0%), control 5 of 101 (5.0%).
risk of ICU admission, 27.1% lower, RR 0.73, p = 0.77, treatment 5 of 99 (5.1%), control 7 of 101 (6.9%).
recovery time, 4.8% lower, relative time 0.95, p = 0.47, treatment 99, control 101.
Ivashkin et al., 10/13/2021, Randomized Controlled Trial, Russia, Europe, peer-reviewed, 11 authors. |
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Levels |
Afaghi et al., The Tohoku Journal of Experimental Medicine, doi:10.1620/tjem.255.127 (Peer Reviewed) |
death, ↓55.0%, p=0.002 |
Prevalence and Clinical Outcomes of Vitamin D Deficiency in COVID-19 Hospitalized Patients: A Retrospective Single-Center Analysis |
| Details Retrospective 646 COVID-19+ hospitalized patients in Iran, showing higher mortality with vitamin D deficiency. |
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Details Source PDF |
| Afaghi et al., The Tohoku Journal of Experimental Medicine, doi:10.1620/tjem.255.127 (Peer Reviewed) |
| Prevalence and Clinical Outcomes of Vitamin D Deficiency in COVID-19 Hospitalized Patients: A Retrospective Single-Center Analysis |
Retrospective 646 COVID-19+ hospitalized patients in Iran, showing higher mortality with vitamin D deficiency. ![]()
risk of death, 55.0% lower, RR 0.45, p = 0.002, high D levels 97 of 537 (18.1%), low D levels 51 of 109 (46.8%), adjusted, OR converted to RR, >20ng/mL, multivariate.
risk of mechanical ventilation, 55.9% lower, RR 0.44, p < 0.001, high D levels 89 of 537 (16.6%), low D levels 41 of 109 (37.6%), >20ng/mL, unadjusted.
risk of ICU admission, 34.1% lower, RR 0.66, p < 0.001, high D levels 211 of 537 (39.3%), low D levels 65 of 109 (59.6%), >20ng/mL, unadjusted.
Afaghi et al., 10/12/2021, retrospective, Iran, Middle East, peer-reviewed, 7 authors. |
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Late |
Hasan et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.10.012 (Peer Reviewed) |
death, ↓92.9%, p=0.0004 |
The Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients |
| Details RCT 158 severe condition patients in Iraq, 82 treated with melatonin, showing lower mortality, thrombosis, and sepsis with treatment. |
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Details Source PDF |
| Hasan et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.10.012 (Peer Reviewed) |
| The Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients |
RCT 158 severe condition patients in Iraq, 82 treated with melatonin, showing lower mortality, thrombosis, and sepsis with treatment. ![]()
risk of death, 92.9% lower, RR 0.07, p < 0.001, treatment 1 of 82 (1.2%), control 13 of 76 (17.1%).
Hasan et al., 10/12/2021, Randomized Controlled Trial, Iraq, Middle East, peer-reviewed, 3 authors. |
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Early |
Majeed et al., Evidence-Based Complementary and Alternative Medicine, doi:10.1155/2021/8447545 (Peer Reviewed) |
ventilation, ↓66.2%, p=1.00 |
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of a Nutritional Supplement (ImmuActive) for COVID-19 Patients |
| Details RCT 100 patients in India, 50 treated with ImmuActive (curcumin, andrographolides, resveratrol, zinc, selenium, and piperine), showing improved recovery with treatment. |
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Details Source PDF |
| Majeed et al., Evidence-Based Complementary and Alternative Medicine, doi:10.1155/2021/8447545 (Peer Reviewed) |
| A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of a Nutritional Supplement (ImmuActive) for COVID-19 Patients |
RCT 100 patients in India, 50 treated with ImmuActive (curcumin, andrographolides, resveratrol, zinc, selenium, and piperine), showing improved recovery with treatment. ![]()
risk of mechanical ventilation, 66.2% lower, RR 0.34, p = 1.00, treatment 0 of 45 (0.0%), control 1 of 47 (2.1%), continuity correction due to zero event.
risk of hospitalization, 79.7% lower, RR 0.20, p = 0.49, treatment 0 of 45 (0.0%), control 2 of 47 (4.3%), continuity correction due to zero event.
relative ordinal scale, 43.0% lower, RR 0.57, p = 0.004, treatment 45, control 47, day 28.
relative time to improve one unit on ordinal scale, 30.1% lower, relative time 0.70, treatment 45, control 47.
risk of no recovery, 24.6% lower, RR 0.75, p = 0.08, treatment 26 of 45 (57.8%), control 36 of 47 (76.6%), day 28.
time to viral-, 5.8% lower, relative time 0.94, p = 0.47, treatment 45, control 47.
Majeed et al., 10/11/2021, Double Blind Randomized Controlled Trial, India, South Asia, peer-reviewed, 4 authors, this trial uses multiple treatments in the treatment arm (combined with curcumin, andrographolides, resveratrol, selenium, and piperine) – results of individual treatments may vary. |
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Review |
Fordham et al., OSF Preprints, doi:10.31219/osf.io/mp4f2 (Review) (Preprint) |
review |
The uses and abuses of systematic reviews |
| Details Analysis of defects in the Popp et al. meta analysis. |
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Details Source PDF |
| Fordham et al., OSF Preprints, doi:10.31219/osf.io/mp4f2 (Review) (Preprint) |
| The uses and abuses of systematic reviews |
Analysis of defects in the Popp et al. meta analysis. ![]() Fordham et al., 10/7/2021, preprint, 4 authors. |
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PrEP |
Wander et al., Diabetes Care, doi:10.2337/dc21-1351 (Peer Reviewed) |
death, ↓15.0%, p<0.0001 |
Prior Glucose-Lowering Medication Use and 30-Day Outcomes Among 64,892 Veterans With Diabetes and COVID-19 |
| Details Retrospective 64,892 veterans with diabetes in the USA, showing lower mortality with existing metformin use. |
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Details Source PDF |
| Wander et al., Diabetes Care, doi:10.2337/dc21-1351 (Peer Reviewed) |
| Prior Glucose-Lowering Medication Use and 30-Day Outcomes Among 64,892 Veterans With Diabetes and COVID-19 |
Retrospective 64,892 veterans with diabetes in the USA, showing lower mortality with existing metformin use. ![]()
risk of death, 15.0% lower, RR 0.85, p < 0.001, treatment 29685, control 35207, OR converted to RR, logistic regression, within 30 days of diagnosis, control prevalance approximated with overall prevalence.
risk of ICU admission, 1.9% lower, RR 0.98, p = 0.59, treatment 29685, control 35207, OR converted to RR, logistic regression, within 30 days of diagnosis, control prevalance approximated with overall prevalence.
risk of hospitalization, 3.2% lower, RR 0.97, p = 0.03, treatment 29685, control 35207, OR converted to RR, logistic regression, within 30 days of diagnosis, control prevalance approximated with overall prevalence.
Wander et al., 10/6/2021, retrospective, database analysis, USA, North America, peer-reviewed, 8 authors. |
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In Silico |
Francés-Monerris et al., Physical Chemistry Chemical Physics, doi:10.1039/D1CP02967C (Peer Reviewed) |
Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection |
| Details In Silico molecular dynamics study showing that ACE2 and ACE2/RBD aggregates form persistent interactions with ivermectin. |
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Details Source PDF |
| Francés-Monerris et al., Physical Chemistry Chemical Physics, doi:10.1039/D1CP02967C (Peer Reviewed) |
| Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection |
| In Silico molecular dynamics study showing that ACE2 and ACE2/RBD aggregates form persistent interactions with ivermectin.Francés-Monerris et al., 10/5/2021, peer-reviewed, 8 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo. |
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Levels |
Mukherjee et al., FEBS Open Bio, doi:10.1002/2211-5463.13309 (Peer Reviewed) |
Seasonal UV exposure and vitamin D: Association with the dynamics of COVID-19 transmission in Europe |
| Details Analysis of UV and temperature levels in 26 European countries, showing that low temperature, UV index, and cloud-free vitamin D UV dose levels are negatively correlated with COVID-19 prevalence. Authors suggest that low UV exposure can a.. |
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Details Source PDF |
| Mukherjee et al., FEBS Open Bio, doi:10.1002/2211-5463.13309 (Peer Reviewed) |
| Seasonal UV exposure and vitamin D: Association with the dynamics of COVID-19 transmission in Europe |
Analysis of UV and temperature levels in 26 European countries, showing that low temperature, UV index, and cloud-free vitamin D UV dose levels are negatively correlated with COVID-19 prevalence. Authors suggest that low UV exposure can affect the required production of vitamin D in the body, which substantially influences the dynamics of COVID-19 transmission and severity. ![]() Mukherjee et al., 10/5/2021, peer-reviewed, 6 authors. |
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PrEP |
Pérez-Segura et al., Medicina Clínica, doi:10.1016/j.medcle.2021.02.010 (Peer Reviewed) |
death, ↑49.1%, p<0.0001 |
Prognostic factors at admission on patients with cancer and COVID-19: Analysis of HOPE registry data |
| Details Retrospective 770 COVID-19 patients with cancer, showing increased mortality with aspirin use in unadjusted results. |
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Details Source PDF |
| Pérez-Segura et al., Medicina Clínica, doi:10.1016/j.medcle.2021.02.010 (Peer Reviewed) |
| Prognostic factors at admission on patients with cancer and COVID-19: Analysis of HOPE registry data |
Retrospective 770 COVID-19 patients with cancer, showing increased mortality with aspirin use in unadjusted results. ![]()
risk of death, 49.1% higher, RR 1.49, p < 0.001, treatment 66 of 155 (42.6%), control 183 of 608 (30.1%), OR converted to RR.
Pérez-Segura et al., 10/4/2021, retrospective, multiple countries, multiple regions, peer-reviewed, 23 authors. |
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PrEP |
Sisinni et al., International Journal of Cardiology, doi:10.1016/j.ijcard.2021.09.058 (Peer Reviewed) |
death, ↑7.1%, p=0.65 |
Pre-admission acetylsalicylic acid therapy and impact on in-hospital outcome in COVID-19 patients: The ASA-CARE study |
| Details Retrospective 984 COVID-19 patients, 253 taking aspirin prior to admission, showing lower risk of respiratory support upgrade with treatment. |
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Details Source PDF |
| Sisinni et al., International Journal of Cardiology, doi:10.1016/j.ijcard.2021.09.058 (Peer Reviewed) |
| Pre-admission acetylsalicylic acid therapy and impact on in-hospital outcome in COVID-19 patients: The ASA-CARE study |
Retrospective 984 COVID-19 patients, 253 taking aspirin prior to admission, showing lower risk of respiratory support upgrade with treatment. ![]()
risk of death, 7.1% higher, RR 1.07, p = 0.65, treatment 93 of 253 (36.8%), control 251 of 731 (34.3%).
risk of death or respiratory support upgrade, 30.3% lower, RR 0.70, p = 0.01, treatment 253, control 731, multivariate.
Sisinni et al., 10/4/2021, retrospective, Italy, Europe, peer-reviewed, 18 authors. |
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Levels |
Abdollahzadeh et al., Infection, Genetics and Evolution, doi:10.1016/j.meegid.2021.105098 (Peer Reviewed) |
Association of Vitamin D receptor gene polymorphisms and clinical/severe outcomes of COVID-19 patients |
| Details Analysis of 500 hospitalized patients in Iran, showing associations between specific vitamin D receceptor gene polymorphisms and COVID-19 outcomes. |
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Details Source PDF |
| Abdollahzadeh et al., Infection, Genetics and Evolution, doi:10.1016/j.meegid.2021.105098 (Peer Reviewed) |
| Association of Vitamin D receptor gene polymorphisms and clinical/severe outcomes of COVID-19 patients |
Analysis of 500 hospitalized patients in Iran, showing associations between specific vitamin D receceptor gene polymorphisms and COVID-19 outcomes. ![]() Abdollahzadeh et al., 10/2/2021, peer-reviewed, 9 authors. |
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Submit Corrections or Comments |
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PrEP |
Basheer et al., Metabolites, doi:10.3390/metabo11100679 (Peer Reviewed) |
death, ↑13.0%, p=0.0003 |
Clinical Predictors of Mortality and Critical Illness in Patients with COVID-19 Pneumonia |
| Details Retrospective 390 hospitalized patients in Israel, showing higher risk of mortality with prior aspirin use. Details of the analysis are not provided. |
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Details Source PDF |
| Basheer et al., Metabolites, doi:10.3390/metabo11100679 (Peer Reviewed) |
| Clinical Predictors of Mortality and Critical Illness in Patients with COVID-19 Pneumonia |
Retrospective 390 hospitalized patients in Israel, showing higher risk of mortality with prior aspirin use. Details of the analysis are not provided. ![]()
risk of death, 13.0% higher, RR 1.13, p < 0.001, treatment 45 of 140 (32.1%), control 29 of 250 (11.6%), adjusted, OR converted to RR, group sizes approximated (only percentages provided).
Basheer et al., 10/2/2021, retrospective, Israel, Middle East, peer-reviewed, 4 authors. |
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N/A |
TrialSite News (News) |
news |
Committed to Medical Evidence, a Prominent Ivermectin Group is Eradicated from the Memories of Cyberspace |
| Details Report on Twitter’s censorship of the British Ivermectin Recommendation Development group. |
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Details Source PDF |
| TrialSite News (News) |
| Committed to Medical Evidence, a Prominent Ivermectin Group is Eradicated from the Memories of Cyberspace |
Report on Twitter’s censorship of the British Ivermectin Recommendation Development group. ![]() TrialSite News et al., 10/2/2021, preprint, 1 author. |
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Late |
Mozaffari et al., Clinical Infectious Diseases, doi:10.1093/cid/ciab875 (Peer Reviewed) |
death, ↓12.0%, p=0.003 |
Remdesivir treatment in hospitalized patients with COVID-19: a comparative analysis of in-hospital all-cause mortality in a large multi-center observational cohort |
| Details Retrospective 28,855 remdesivir patients with PSM matched controls, showing lower mortality with treatment. |
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Details Source PDF |
| Mozaffari et al., Clinical Infectious Diseases, doi:10.1093/cid/ciab875 (Peer Reviewed) |
| Remdesivir treatment in hospitalized patients with COVID-19: a comparative analysis of in-hospital all-cause mortality in a large multi-center observational cohort |
Retrospective 28,855 remdesivir patients with PSM matched controls, showing lower mortality with treatment. ![]()
risk of death, 12.0% lower, RR 0.88, p = 0.003, treatment 4,441 of 28,855 (15.4%), control 5,499 of 28,855 (19.1%), adjusted, 28 days, PSM, Cox proportional hazards.
risk of death, 24.0% lower, RR 0.76, p < 0.001, treatment 3,057 of 28,855 (10.6%), control 4,437 of 28,855 (15.4%), adjusted, 14 days, PSM, Cox proportional hazards.
Mozaffari et al., 10/1/2021, retrospective, USA, North America, peer-reviewed, 12 authors. |
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Late |
Zhao et al., Anesthesiology, doi:10.1097/ALN.0000000000003999 (Peer Reviewed) |
death, ↓43.0%, p=0.0006 |
Treatments Associated with Lower Mortality among Critically Ill COVID-19 Patients: A Retrospective Cohort Study |
| Details Retrospective 2,070 hospitalized patients in the USA, showing lower mortality with aspirin treatment. |
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Details Source PDF |
| Zhao et al., Anesthesiology, doi:10.1097/ALN.0000000000003999 (Peer Reviewed) |
| Treatments Associated with Lower Mortality among Critically Ill COVID-19 Patients: A Retrospective Cohort Study |
Retrospective 2,070 hospitalized patients in the USA, showing lower mortality with aspirin treatment. ![]()
risk of death, 43.0% lower, RR 0.57, p < 0.001, treatment 121 of 473 (25.6%), control 140 of 473 (29.6%), adjusted, PSM.
risk of death, 28.0% lower, RR 0.72, p = 0.03, treatment 473, control 1597, adjusted, multivariable.
Zhao et al., 10/1/2021, retrospective, USA, North America, peer-reviewed, 6 authors. |
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Early |
Merck News Release (News) |
death, ↓94.2%, p=0.003 |
Merck and Ridgeback’s Investigational Oral Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19 in Positive Interim Analysis of Phase 3 Study |
| Details News release reporting interim analysis of the MOVe-OUT trial, showing significantly lower risk of hospitalization or death. NCT04575597. |
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Details Source PDF |
| Merck News Release (News) |
| Merck and Ridgeback’s Investigational Oral Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19 in Positive Interim Analysis of Phase 3 Study |
News release reporting interim analysis of the MOVe-OUT trial, showing significantly lower risk of hospitalization or death. NCT04575597.
risk of death, 94.2% lower, RR 0.06, p = 0.003, treatment 0 of 385 (0.0%), control 8 of 377 (2.1%), continuity correction due to zero event.
risk of combined hospitalization/death, 48.3% lower, RR 0.52, p = 0.001, treatment 28 of 385 (7.3%), control 53 of 377 (14.1%).
Merck et al., 10/1/2021, Randomized Controlled Trial, multiple countries, multiple regions, preprint, 1 author. |
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Late |
Babalola et al., Research Square, doi:10.21203/rs.3.rs-950352/v1 (Preprint) |
no disch., ↑54.5%, p=0.20 |
A Randomized Controlled Trial of Ivermectin Monotherapy Versus Hydroxychloroquine, Ivermectin, and Azithromycin Combination Therapy in Covid-19 Patients in Nigeria |
| Details Small RCT with 61 patients in Nigeria, all patients treated with ivermectin, zinc, and vitamin C, showing no significant improvements in recovery with the addition of HCQ+AZ. PACTR202108891693522. |
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Details Source PDF |
| Babalola et al., Research Square, doi:10.21203/rs.3.rs-950352/v1 (Preprint) |
| A Randomized Controlled Trial of Ivermectin Monotherapy Versus Hydroxychloroquine, Ivermectin, and Azithromycin Combination Therapy in Covid-19 Patients in Nigeria |
Small RCT with 61 patients in Nigeria, all patients treated with ivermectin, zinc, and vitamin C, showing no significant improvements in recovery with the addition of HCQ+AZ. PACTR202108891693522.
risk of no hospital discharge, 54.5% higher, RR 1.55, p = 0.20, treatment 17 of 30 (56.7%), control 11 of 30 (36.7%), day 7.
risk of no virological cure, 9.5% lower, RR 0.90, p = 0.78, treatment 19 of 30 (63.3%), control 21 of 30 (70.0%), day 5 mid-recovery.
Babalola et al., 10/1/2021, Single Blind Randomized Controlled Trial, Nigeria, Africa, preprint, 6 authors, this trial uses multiple treatments in the treatment arm (combined with AZ) – results of individual treatments may vary. |
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PrEP |
Fung et al., medRxiv, doi:10.1101/2021.09.28.21264186 (Preprint) |
death, ↓15.0%, p=0.10 |
Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients |
| Details Retrospective database analysis of 374,229 patients in the USA, showing no significant difference with HCQ use, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research sh.. |
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Details Source PDF |
| Fung et al., medRxiv, doi:10.1101/2021.09.28.21264186 (Preprint) |
| Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients |
Retrospective database analysis of 374,229 patients in the USA, showing no significant difference with HCQ use, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [1]. Authors compare with patients that never used HCQ and with patients that previously used HCQ. The comparison with patients previously using HCQ is more relevant because the matching of patients with systemic autoimmune disease is likely to be better. ![]()
risk of death, 15.0% lower, RR 0.85, p = 0.10, vs. past use (better match for systemic autoimmune diseases).
risk of hospitalization, 5.0% lower, RR 0.95, p = 0.41, vs. past use (better match for systemic autoimmune diseases).
risk of COVID-19 case, 10.0% lower, RR 0.90, p = 0.004, vs. past use (better match for systemic autoimmune diseases).
risk of death, 6.0% higher, RR 1.06, p = 0.39, vs. never used.
risk of hospitalization, 4.0% higher, RR 1.04, p = 0.32, vs. never used.
risk of COVID-19 case, 5.0% lower, RR 0.95, p = 0.06, vs. never used.
Fung et al., 10/1/2021, retrospective, population-based cohort, USA, North America, preprint, 6 authors. |
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Late |
Menardi et al., PharmAdvances, doi:10.36118/pharmadvances.2021.15 (Peer Reviewed) |
death, ↓35.2%, p=0.12 |
A retrospective analysis on pharmacological approaches to COVID-19 patients in an Italian hub hospital during the early phase of the pandemic |
| Details Retrospective 277 hospitalized patients in Italy, showing lower mortality with HCQ treatment, not reaching statistical significance, and subject to confounding by indication. |
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Details Source PDF |
| Menardi et al., PharmAdvances, doi:10.36118/pharmadvances.2021.15 (Peer Reviewed) |
| A retrospective analysis on pharmacological approaches to COVID-19 patients in an Italian hub hospital during the early phase of the pandemic |
Retrospective 277 hospitalized patients in Italy, showing lower mortality with HCQ treatment, not reaching statistical significance, and subject to confounding by indication. ![]()
risk of death, 35.2% lower, RR 0.65, p = 0.12, treatment 32 of 200 (16.0%), control 19 of 77 (24.7%).
Menardi et al., 9/30/2021, retrospective, Italy, Europe, peer-reviewed, 10 authors. |
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Animal |
Cecon et al., Journal of Pineal Research, doi:10.1111/jpi.12772 (Peer Reviewed) |
animal study |
Therapeutic potential of melatonin and melatonergic drugs on K18-hACE2 mice infected with SARS-CoV-2 |
| Details Study of melatonin and melatonergic compounds with mice expressing the human ACE2 receptor (K18-hACE2). Daily administration of melatonin, agomelatine or ramelteon delayed the occurrence of severe clinical outcome with improvement of surv.. |
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Details Source PDF |
| Cecon et al., Journal of Pineal Research, doi:10.1111/jpi.12772 (Peer Reviewed) |
| Therapeutic potential of melatonin and melatonergic drugs on K18-hACE2 mice infected with SARS-CoV-2 |
Study of melatonin and melatonergic compounds with mice expressing the human ACE2 receptor (K18-hACE2). Daily administration of melatonin, agomelatine or ramelteon delayed the occurrence of severe clinical outcome with improvement of survival, especially with high melatonin dose. ![]() Cecon et al., 9/29/2021, peer-reviewed, 11 authors. |
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In Silico |
Şimşek et al., Journal of Molecular Graphics and Modelling, doi:10.1016/j.jmgm.2021.108038 (Peer Reviewed) |
In silico identification of SARS-CoV-2 cell entry inhibitors from selected natural antivirals |
| Details In SIlico study identifying quercetin derivatives as SARS-CoV-2 spike protein, ACE2, and neuropilin inhibitors. |
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Details Source PDF |
| Şimşek et al., Journal of Molecular Graphics and Modelling, doi:10.1016/j.jmgm.2021.108038 (Peer Reviewed) |
| In silico identification of SARS-CoV-2 cell entry inhibitors from selected natural antivirals |
In SIlico study identifying quercetin derivatives as SARS-CoV-2 spike protein, ACE2, and neuropilin inhibitors. ![]() Şimşek et al., 9/29/2021, peer-reviewed, 3 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo. |
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Late |
Simsek et al., Annals of Medical Research, doi:10.5455/annalsmedres.2020.10.1043 (Peer Reviewed) |
death, ↓44.1%, p=0.18 |
Effects of high dose vitamin C administration in Covid-19 patients |
| Details Retrospective 139 hospitalized patients in Turkey, 58 treated with high dose vitamin C, showing improved kidney functioning with treatment. Mortality was lower with treatment, but not reaching statistical significance with the small sampl.. |
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Details Source PDF |
| Simsek et al., Annals of Medical Research, doi:10.5455/annalsmedres.2020.10.1043 (Peer Reviewed) |
| Effects of high dose vitamin C administration in Covid-19 patients |
Retrospective 139 hospitalized patients in Turkey, 58 treated with high dose vitamin C, showing improved kidney functioning with treatment. Mortality was lower with treatment, but not reaching statistical significance with the small sample size. ![]()
risk of death, 44.1% lower, RR 0.56, p = 0.18, treatment 6 of 58 (10.3%), control 15 of 81 (18.5%).
risk of ICU admission, 10.2% lower, RR 0.90, p = 0.66, treatment 18 of 58 (31.0%), control 28 of 81 (34.6%).
Simsek et al., 9/27/2021, retrospective, Turkey, Europe, peer-reviewed, 16 authors. |
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Late |
Yildiz et al., Bratislava Medical Journal, doi:10.4149/BLL_2021_119 (Peer Reviewed) |
death, ↓80.9%, p=0.04 |
The prognostic significance of vitamin D deficiency in patients with COVID-19 pneumonia |
| Details Retrospective 207 hospitalized patients in Turkey, 37 with vitamin D levels <30ng/ml treated with a 300,000IU vitamin D, showing lower mortality with treatment. |
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Details Source PDF |
| Yildiz et al., Bratislava Medical Journal, doi:10.4149/BLL_2021_119 (Peer Reviewed) |
| The prognostic significance of vitamin D deficiency in patients with COVID-19 pneumonia |
Retrospective 207 hospitalized patients in Turkey, 37 with vitamin D levels <30ng/ml treated with a 300,000IU vitamin D, showing lower mortality with treatment. ![]()
risk of death, 80.9% lower, RR 0.19, p = 0.04, treatment 1 of 37 (2.7%), control 24 of 170 (14.1%).
risk of ICU admission, 94.5% lower, RR 0.06, p = 0.13, treatment 0 of 37 (0.0%), control 14 of 170 (8.2%), continuity correction due to zero event.
hospitalization time, 9.6% lower, relative time 0.90, p = 0.32, treatment 37, control 170.
Yildiz et al., 9/27/2021, retrospective, Turkey, Europe, peer-reviewed, 5 authors, dosage 300,000IU single dose. |
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Meta |
Borsche et al., medRxiv, doi:10.1101/2021.09.22.21263977 (Preprint) (meta analysis) |
meta-analysis |
COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3: Results of a systematic review and meta-analysis |
| Details Meta analysis of 8 studies with vitamin D levels measured pre-infection or on the day of hospital admission, showing a correlation between the levels and mortality. Authors recommend combining vaccination with vitamin D supplementation to.. |
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Details Source PDF |
| Borsche et al., medRxiv, doi:10.1101/2021.09.22.21263977 (Preprint) (meta analysis) |
| COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3: Results of a systematic review and meta-analysis |
Meta analysis of 8 studies with vitamin D levels measured pre-infection or on the day of hospital admission, showing a correlation between the levels and mortality. Authors recommend combining vaccination with vitamin D supplementation to maintain levels above 50 ng/ml. Authors extrapolate to predict a point of zero mortality, however there is no reason to predict a linear relationship where zero mortality would be reached. ![]() Borsche et al., 9/25/2021, preprint, 3 authors. |
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PrEP |
Arroyo-Díaz et al., Frontiers in Public Health, doi:10.3389/fpubh.2021.758347 (Peer Reviewed) |
death, ↑12.4%, p=0.51 |
Previous Vitamin D Supplementation and Morbidity and Mortality Outcomes in People Hospitalised for COVID19: A Cross-Sectional Study |
| Details Retrospective 1,267 hospitalized patients in Spain, 189 on vitamin D supplementation before admission, showing lower ICU admission with supplementation, and no statistically significant difference for mortality or ventilation. |
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Details Source PDF |
| Arroyo-Díaz et al., Frontiers in Public Health, doi:10.3389/fpubh.2021.758347 (Peer Reviewed) |
| Previous Vitamin D Supplementation and Morbidity and Mortality Outcomes in People Hospitalised for COVID19: A Cross-Sectional Study |
Retrospective 1,267 hospitalized patients in Spain, 189 on vitamin D supplementation before admission, showing lower ICU admission with supplementation, and no statistically significant difference for mortality or ventilation. ![]()
risk of death, 12.4% higher, RR 1.12, p = 0.51, treatment 50 of 189 (26.5%), control 167 of 1,078 (15.5%), adjusted, OR converted to RR.
risk of mechanical ventilation, 43.3% lower, RR 0.57, p = 0.18, treatment 11 of 189 (5.8%), control 113 of 1,078 (10.5%), adjusted, OR converted to RR.
risk of ICU admission, 44.2% lower, RR 0.56, p = 0.03, treatment 13 of 189 (6.9%), control 133 of 1,078 (12.3%), unadjusted.
hospitalization time, 11.8% lower, relative time 0.88, p = 0.20, treatment 189, control 1078, unadjusted.
Arroyo-Díaz et al., 9/24/2021, retrospective, Spain, Europe, peer-reviewed, 11 authors, dosage not specified. |
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Early |
Mayer et al., Zenodo, doi:10.5281/zenodo.5525362 (Preprint) |
death, ↓55.1%, p<0.0001 |
Safety and efficacy of a MEURI Program for the use of high dose ivermectin in COVID-19 patients |
| Details Retrospective 21,232 patients in Argentina, 3,266 assigned to ivermectin treatment, showing lower mortality with treatment. Greater benefits were seen for patients >40, and a dose dependent response was found. |
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Details Source PDF |
| Mayer et al., Zenodo, doi:10.5281/zenodo.5525362 (Preprint) |
| Safety and efficacy of a MEURI Program for the use of high dose ivermectin in COVID-19 patients |
Retrospective 21,232 patients in Argentina, 3,266 assigned to ivermectin treatment, showing lower mortality with treatment. Greater benefits were seen for patients >40, and a dose dependent response was found. ![]()
risk of death, 55.1% lower, RR 0.45, p < 0.001, treatment 3266, control 17966, adjusted, OR converted to RR, multiple logistic regression, Figure 3.
risk of ICU admission, 65.9% lower, RR 0.34, p < 0.001, treatment 3266, control 17966, adjusted, OR converted to RR, multiple logistic regression, Figure 3.
risk of death, 27.6% lower, RR 0.72, p = 0.03, treatment 3266, control 17966, OR converted to RR, unadjusted.
risk of ICU admission, 26.0% lower, RR 0.74, p = 0.13, treatment 3266, control 17966, OR converted to RR, unadjusted.
Mayer et al., 9/23/2021, retrospective, Argentina, South America, preprint, 14 authors, dosage 540μg/kg days 1-5, mean prescribed dose. |
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Late |
Dorward et al., medRxiv, doi:2021.09.20.21263828 (Preprint) |
hosp./death, ↑29.8%, p=0.65 |
Colchicine for COVID-19 in adults in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial |
| Details Late treatment RCT with 156 colchicine patients in the UK, showing no significant differences. ISRCTN86534580. |
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Details Source PDF |
| Dorward et al., medRxiv, doi:2021.09.20.21263828 (Preprint) |
| Colchicine for COVID-19 in adults in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial |
Late treatment RCT with 156 colchicine patients in the UK, showing no significant differences. ISRCTN86534580. ![]()
risk of combined hospitalization/death, 29.8% higher, RR 1.30, p = 0.65, treatment 6 of 156 (3.8%), control 4 of 133 (3.0%), OR converted to RR, concurrent randomisation.
risk of combined hospitalization/death, 22.1% lower, RR 0.78, p = 0.55, treatment 6 of 156 (3.8%), control 119 of 1,145 (10.4%), OR converted to RR, including control patients before the colchicine arm started.
risk of disease progression, 6.0% lower, RR 0.94, p = 0.45, treatment 102 of 156 (65.4%), control 83 of 120 (69.2%).
risk of no recovery, 6.0% lower, RR 0.94, p = 0.67, treatment 156, control 133, time to alleviation of symptoms.
Dorward et al., 9/23/2021, Randomized Controlled Trial, United Kingdom, Europe, preprint, 21 authors. |
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Review |
Castle et al., Journal of Inflammation Research, doi:10.2147/JIR.S323356 (Review) (Peer Reviewed) |
review |
Implications for Systemic Approaches to COVID-19: Effect Sizes of Remdesivir, Tocilizumab, Melatonin, Vitamin D3, and Meditation |
| Details Review of the effects of COVID-19 on inflammatory markers, and the effects on those markers of standard treatments vs. vitamin D, melatonin, and meditation, showing comparable or superior effects with the non-standard treatments. The stan.. |
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Details Source PDF |
| Castle et al., Journal of Inflammation Research, doi:10.2147/JIR.S323356 (Review) (Peer Reviewed) |
| Implications for Systemic Approaches to COVID-19: Effect Sizes of Remdesivir, Tocilizumab, Melatonin, Vitamin D3, and Meditation |
Review of the effects of COVID-19 on inflammatory markers, and the effects on those markers of standard treatments vs. vitamin D, melatonin, and meditation, showing comparable or superior effects with the non-standard treatments. The standard treatments in this study were remdesivir and tocilizumab. We note that standard treatments vary widely around the world, for example vitamin D is a standard treatment in many locations. ![]() Castle et al., 9/22/2021, peer-reviewed, 8 authors. |
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Levels |
Laing et al., Nutrients, doi:10.3390/nu13103304 (Peer Reviewed) |
death, ↓79.0%, p=0.01 |
Course and Survival of COVID-19 Patients with Comorbidities in Relation to the Trace Element Status at Hospital Admission |
| Details Retrospective 79 hospitalized patients in Belgium, showing mortality associated with zinc and selenium deficiency. |
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Details Source PDF |
| Laing et al., Nutrients, doi:10.3390/nu13103304 (Peer Reviewed) |
| Course and Survival of COVID-19 Patients with Comorbidities in Relation to the Trace Element Status at Hospital Admission |
Retrospective 79 hospitalized patients in Belgium, showing mortality associated with zinc and selenium deficiency. ![]()
risk of death, 79.0% lower, RR 0.21, p = 0.01, high zinc levels 3 of 49 (6.1%), low zinc levels 7 of 24 (29.2%).
Laing et al., 9/22/2021, retrospective, Belgium, Europe, peer-reviewed, 11 authors. |
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Levels |
Marino-Ramirez et al., medRxiv, doi:10.1101/2021.09.20.21263865 (Preprint) |
Vitamin D and socioeconomic deprivation mediate COVID-19 ethnic health disparities |
| Details UK Biobank retrospective showing that vitamin supplements, including vitamin D, mediate the Asian disparity in COVID-19 susceptibility, and vitamin D levels mediate Asian and Black COVID-19 severity disparities. Authors conclude that the .. |
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Details Source PDF |
| Marino-Ramirez et al., medRxiv, doi:10.1101/2021.09.20.21263865 (Preprint) |
| Vitamin D and socioeconomic deprivation mediate COVID-19 ethnic health disparities |
UK Biobank retrospective showing that vitamin supplements, including vitamin D, mediate the Asian disparity in COVID-19 susceptibility, and vitamin D levels mediate Asian and Black COVID-19 severity disparities. Authors conclude that the results support the use of vitamin D as both a prophylactic and a supplemental therapeutic for COVID-19 in those individuals. ![]() Marino-Ramirez et al., 9/22/2021, preprint, 7 authors. |
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Levels |
Derakhshanian et al., Food Science & Nutrition, doi:10.1002/fsn3.2591 (Peer Reviewed) |
death, ↓44.8%, p=0.02 |
The predictive power of serum vitamin D for poor outcomes in COVID-19 patients |
| Details Retrospective 290 hospitalized patients in Iran, showing higher mortality with vitamin D deficiency. |
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Details Source PDF |
| Derakhshanian et al., Food Science & Nutrition, doi:10.1002/fsn3.2591 (Peer Reviewed) |
| The predictive power of serum vitamin D for poor outcomes in COVID-19 patients |
Retrospective 290 hospitalized patients in Iran, showing higher mortality with vitamin D deficiency. ![]()
risk of death, 44.8% lower, RR 0.55, p = 0.02, high D levels 148, low D levels 142, OR converted to RR, control prevalance approximated with overall prevalence.
risk of mechanical ventilation, 41.7% lower, RR 0.58, p = 0.05, high D levels 148, low D levels 142, OR converted to RR, control prevalance approximated with overall prevalence.
risk of ICU admission, 37.3% lower, RR 0.63, p = 0.007, high D levels 148, low D levels 142, OR converted to RR, control prevalance approximated with overall prevalence.
Derakhshanian et al., 9/19/2021, retrospective, Iran, Middle East, peer-reviewed, 11 authors. |
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Late |
Hassaniazad et al., Phytotherapy Research, doi:10.1002/ptr.7294 (Peer Reviewed) |
no recov., ↑45.7%, p=0.90 |
A triple-blind, placebo-controlled, randomized clinical trial to evaluate the effect of curcumin-containing nanomicelles on cellular immune responses subtypes and clinical outcome in COVID-19 patients |
| Details Small RCT with 40 low risk patients in Iran, 20 treated with nano-curcumin, showing no significant difference in outcomes with treatment. Authors note that treatment can improve peripheral blood inflammatory indices and modulate immune re.. |
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Details Source PDF |
| Hassaniazad et al., Phytotherapy Research, doi:10.1002/ptr.7294 (Peer Reviewed) |
| A triple-blind, placebo-controlled, randomized clinical trial to evaluate the effect of curcumin-containing nanomicelles on cellular immune responses subtypes and clinical outcome in COVID-19 patients |
Small RCT with 40 low risk patients in Iran, 20 treated with nano-curcumin, showing no significant difference in outcomes with treatment. Authors note that treatment can improve peripheral blood inflammatory indices and modulate immune response by decreasing Th1 and Th17 responses, increasing T regulatory responses, further reducing IL-17 and IFN-γ, and increasing suppressive cytokines TGF-β and IL-4. ![]()
relative improvement in SpO2, 45.7% higher, RR 1.46, p = 0.90, treatment 20, control 20.
Hassaniazad et al., 9/19/2021, Double Blind Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 12 authors. |
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Jitaboam et al., 10/14/2021, peer-reviewed, 8 authors.
Fordham et al., 10/7/2021, preprint, 4 authors.
Mukherjee et al., 10/5/2021, peer-reviewed, 6 authors.
Abdollahzadeh et al., 10/2/2021, peer-reviewed, 9 authors.
TrialSite News et al., 10/2/2021, preprint, 1 author.
Cecon et al., 9/29/2021, peer-reviewed, 11 authors.
Şimşek et al., 9/29/2021, peer-reviewed, 3 authors.
Borsche et al., 9/25/2021, preprint, 3 authors.
Castle et al., 9/22/2021, peer-reviewed, 8 authors.
Marino-Ramirez et al., 9/22/2021, preprint, 7 authors.
