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| Meta | Shah et al., QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcac040 (Peer Reviewed) (meta analysis) | death, ↓52.1%, p<0.0001 | Does vitamin D supplementation reduce COVID-19 severity? - a systematic review |
| Details Meta-analysis of seven systematic reviews showing that vitamin D supplementation reduces the risk of COVID-19 mortality, ventilation, and ICU admission. Authors note that oral and IV supplements were well tolerated, safe, and effective. |
| Late | Al Mutair et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2022.01.013 (Peer Reviewed) | death, ↓7.0%, p=0.49 | Overview of Clinical Outcome and Therapeutic Effectiveness of Favipiravir in Patients with COVID-19 Admitted to Intensive Care Unit, Riyadh, Saudi Arabia |
| Details Retrospective 269 favipiravir ICU patients in Saudi Arabia and 269 matched controls receiving different treatments, showing no significant difference. |
| Early | Lowe et al., medRxiv, doi:10.1101/2022.02.11.22270775 (Preprint) | ICU, ↑196.3%, p=1.00 | Favipiravir, lopinavir-ritonavir or combination therapy (FLARE): a randomised, double blind, 2x2 factorial placebo-controlled trial of early antiviral therapy in COVID-19 |
| Details 240 patient RCT comparing favipiravir, favipiravir + LPV/r, LPV/r, and placebo, showing improved viral clearance with favipiravir. Efficacy was lower in the combined favipiravir + LPV/r arm, where plasma levels of favipiravir were lower. .. |
| Late | Beaumont et al., Infectious Diseases Now, doi:10.1016/j.idnow.2022.02.001 (Peer Reviewed) | death/int., ↓14.1%, p=0.55 | Factors associated with hospital admission and adverse outcome for COVID-19: role of social factors and medical care |
| Details Retrospective 296 hospitalized patients in France, showing no significant difference with HCQ treatment. |
| Early | Lilly (Preprint) | death, ↑150.8%, p=1.00 | A Study of Immune System Proteins in Participants With Mild to Moderate COVID-19 Illness |
| Details RCT with 127 bamlanivimab, etesevimab, and bebtelovimab patients, 125 bebtelovimab patients, and 128 control patients, showing no significant differences in hospitalization and mortality. Viral clearance was improved although not statisti.. |
| Early | Brennan et al., Gut, doi:10.1136/gutjnl-2022-326952 (Peer Reviewed) | no recov., ↓48.1%, p=0.23 | Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial |
| Details Small RCT with 27 famotidine and 28 placebo patients, showing improved recovery with treatment. Recovery was faster with treatment for 14 of 16 symptoms. There was no mortality or hospitalization. NCT04724720. |
| Early | Friedland et al., Australian Journal of Otolaryngology, doi:10.21037/ajo-21-40 (Peer Reviewed) | In vivo (human) and in vitro inactivation of SARS-CoV-2 with 0.5% povidone-iodine nasal spray |
| Details Small study of povidone-iodine nasal spray with 14 patients, showing rapid reduction in viral load for the 6 patients that had culturable virus at baseline. All patients remained PCR+ despite no culturable virus detected for 3 of 6 patien.. |
| Early | Dale et al., Journal of the American Geriatrics Society, doi:10.1111/jgs.17705 (Peer Reviewed) | death, ↓89.2%, p=0.010 | Clinical Outcomes of Monoclonal Antibody Therapy During a COVID ‐19 Outbreak in a Skilled Nursing Facility‐Arizona, 2021 |
| Details Retrospective 75 COVID+ patients in a skilled nursing facility in the USA, 56 treated within a median of 2 days from symptom onset with bamlanivimab, showing significantly lower mortality with treatment. |
| Animal | Miorin et al., bioRxiv, doi:10.1101/2022.02.08.479634 (Preprint) | animal study | The oral drug nitazoxanide restricts SARS-CoV-2 infection and attenuates disease pathogenesis in Syrian hamsters |
| Details In Vitro study showing that nitazoxanide inhibits SARS-CoV-2 in H9, iAT2, Vero E6, Vero TMPRSS2, and Ace2-A549 cells. Syrian hamster study showing improvements in SARS-CoV-2 related weight loss, inflammation, viral load, and lung synctia.. |
| Levels | Ivanova et al., Journal of Trace Elements in Medicine and Biology, doi:10.1016/j.jtemb.2022.126944 (Peer Reviewed) | Evaluation of zinc, copper, and Cu:Zn ratio in serum, and their implications in the course of COVID-19 |
| Details Retrospective 75 COVID-19 hospitalized patients and 68 healthy controls in Bulgaria, showing mortality associated with lower zinc levels. |
| Late | Bishop et al., medRxiv, doi:10.1101/2022.01.31.22270036 (Preprint) | no recov., ↓33.7%, p=0.56 | Results From the REsCue Trial: A Randomized Controlled Trial with Extended-Release Calcifediol in Symptomatic Outpatients with COVID-19 |
| Details Small RCT with low-risk patients in Florida, USA, showing no significant differences in overall recovery. Minimal details on outcomes are provided in the preprint. Authors note significantly faster resolution of respiratory symptoms when .. |
| Late | Sánchez-Rico et al., Journal of Travel Medicine, doi:10.1093/jtm/taab195 (Peer Reviewed) | death, ↓19.0%, p=0.15 | Melatonin does not reduce mortality in adult hospitalized patients with COVID-19: a multicenter retrospective observational study |
| Details Retrospective database analysis in France with 272 patients treated with melatonin, showing 19% lower mortality after adjustments, without statistical significance. Risk was lower for higher dosage (not statistically significant). Age was.. |
| Late | Fowotade et al., medRxiv, doi:10.1101/2022.02.03.22270152 (Preprint) | no recov., ↑11.4%, p=0.72 | Efficacy and safety of nitazoxanide combined with ritonavir-boosted atazanavir for the treatment of mild to moderate COVID-19 |
| Details Small RCT in Nigeria with 31 nitazoxanide and atazanavir/ritonavir patients, and 26 control patients, showing no significant differences with treatment. 4 treatment group patients discontinued treatment due to the size of the tablets. Tim.. |
| Review | Swanstrom et al., Science, doi:10.1126/science.abn0048 (Review) (Peer Reviewed) | review | Lethal mutagenesis as an antiviral strategy |
| Details Review of the unknown long-term cancer, reproductive, and escape variant creation risks of molnupiravir. For more discussion see [1, 2, 3]. |
| Late | Albanghali et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2022.02.001 (Peer Reviewed) | death, ↑34.6%, p=0.46 | Clinical Characteristics and Treatment Outcomes of Mild to Moderate Covid-19 Patients in Saudi Arabia: A Single Centre Study |
| Details Retrospective 811 hospitalized COVID+ patients in Saudi Arabia, showing higher mortality with HCQ treatment in unadjusted results subject to confounding by indication. |
| Late | Pourdowlat et al., Phytotherapy Research, doi:10.1002/ptr.7319 (Peer Reviewed) | hosp., ↓72.8%, p=0.004 | Efficacy and safety of colchicine treatment in patients with COVID-19: A prospective, multicenter, randomized clinical trial |
| Details RCT 202 patients in Iran, 102 treated with colchicine, showing lower hospitalization and improved clinical outcomes with treatment. |
| Early | Manomaipiboon et al., Research Square, doi:10.21203/rs.3.rs-1290999/v1 (Preprint) | no recov., ↓43.5%, p=0.26 | Efficacy and safety of ivermectin in the treatment of mild-to-moderate COVID-19 infection: A randomized, double blind, placebo, controlled trial |
| Details Small RCT with 72 low-risk patients in Thailand, showing improved recovery with ivermectin, without statistical significance. All patients recovered and there was no escalation of care in either group. There were no adverse events. |
| Late | Turan et al., The Brazilian Journal of Infectious Diseases, doi:10.1016/j.bjid.2022.102328 (Peer Reviewed) | hosp., ↓79.4%, p=0.001 | The effect of favipiravir versus hydroxychloroquine on clinical and laboratory findings in COVID-19 in healthcare workers |
| Details Retrospective 237 low-risk healthcare workers in Turkey, 123 treated with favipiravir and 114 treated with HCQ, showing lower hospitalization and faster viral clearance with favipiravir, and similar improvement. This study is subject to s.. |
| Early | Shopen et al., medRxiv, doi:10.1101/2022.01.29.22270090 (Preprint) | severe case, ↑45.6%, p=0.26 | Doubtful Clinical Benefit of Casirivimab-Imdevimab Treatment for Disease Severity Outcome of High-Risk Patients with SARS-CoV-2 Delta Variant Infection |
| Details Retrospective 359 COVID+ patients in Israel, 116 treated with casirivimab/imdevimab, showing no significant difference with treatment in multivariable analysis. |
| Review | Tan et al., Life Sciences, doi:10.1016/j.lfs.2022.120368 (Review) (Peer Reviewed) | review | Mechanisms and clinical evidence to support melatonin's use in severe COVID-19 patients to lower mortality |
| Details Review of the mechanisms of action and clinical evidence supporting the use of melatonin for severe COVID-19. |
| In Vitro | Kowa News Release (News) (In Vitro) | news | Antiviral effect of ivermectin confirmed for omicron |
| Details Kowa reports that ivermectin is effective for omicron in In Vitro research. |
| PrEP | Subramanian et al., The American Journal of Clinical Nutrition, doi:10.1093/ajcn/nqac027 (Peer Reviewed) | death, ↓27.3%, p=0.12 | Vitamin D, D-binding protein, free vitamin D and COVID-19 mortality in hospitalized patients |
| Details Retrospective 427 hospitalized COVID-19 patients in the United Kingdom, showing lower mortality with vitamin D supplementation (p=0.12), and higher mortality with both low and high vitamin D levels compared to a reference range of 50-74 n.. |
| PrEP | Mohajeri et al., Mediterranean Journal of Nutrition and Metabolism, doi:10.3233/MNM-211521 (Peer Reviewed) | The difference in the dietary inflammatory index, functional food, and antioxidants intake between COVID -19 patients and healthy persons |
| Details Retrospective dietary survey analysis of 500 COVID-19 patients and 500 healthy matched controls in Iran, showing that COVID-19 patients had lower daily consumption of vitamin C, vitamin D, vitamin E, zinc, and selenium. IR.ARUMS.REC.1400... |
| Late | Kartika et al., ICE on IMERI, 2021 (Preprint) | hosp. time, ↓41.0%, p=0.048 | Curcumin as adjuvant Therapy in Mild - Moderate Covid 19 |
| Details Retrospective 246 hospitalized patients in Indonesia, 136 treated with curcumin, showing shorter hospitalization time with treatment. All patients received vitamin C, D, and zinc. |
| Early | Delasobera et al., Infectious Diseases in Clinical Practice, doi:10.1097/IPC.0000000000001109 (Peer Reviewed) | death, ↑119.4%, p=0.64 | Impact of Rapidly Deployed COVID-19 Monoclonal Antibody Infusion Clinics on Rate of Hospitalization |
| Details Retrospective 438 patients in the USA, 253 treated with bamlanivimab, showing significantly lower hospitalization with treatment. |
| Late | Priest et al., Infectious Diseases in Clinical Practice, doi:10.1097/IPC.0000000000001130 (Peer Reviewed) | death, 0.0%, p=1.00 | Bamlanivimab for the Prevention of Hospitalizations and Emergency Department Visits in SARS-CoV-2–Positive Patients in a Regional Health Care System |
| Details Retrospective 379 bamlanivimab patients and 379 matched controls in the USA, showing no significant differences with treatment. |
| Levels | Schmitt et al., Journal of Medical Virology, doi:10.1002/jmv.27606 (Peer Reviewed) | Oxidative stress status and vitamin D levels of asymptomatic to mild symptomatic COVID-19 infections during the third trimester of pregnancy: A retrospective study in Metz, France |
| Details Retrospective 15 COVID+ pregnant women and 20 healthy controls in France, showing that all COVID+ patients were vitamin D deficient, and vitamin D levels were significantly lower in symptomatic patients compared to controls or asymptomati.. |
| Late | Izquierdo et al., Science Progress, doi:10.1177/00368504221074574 (Peer Reviewed) | death, ↓25.6%, p=0.0007 | Use of N-Acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19 |
| Details Retrospective 19,208 COVID+ hospitalized patients in Spain, 2,071 treated with high dose NAC, showing lower mortality with treatment. In multivariable analysis, authors adjust for corticosteroids, but do not adjust for HCQ use which was a.. |
| In Silico | Kumar Yadalam et al., Saudi Journal of Biological Sciences, doi:10.1016/j.sjbs.2022.01.049 (Peer Reviewed) | In Silico | Assessing the therapeutic potential of angomelatine, ramelteon, and melatonin against SARS-Cov-2 |
| Details In Silico study of melatonin, angomelatine, and ramelteon for SARS-CoV-2, predicting significant SARS-CoV-2 RBD and ACE2 binding with all three. |
| PrEP, PEP | Garcia-Albeniz et al., medRxiv, doi:10.1101/2020.09.29.20203869 (Preprint) (meta analysis) | cases, ↓28.0%, p=0.004 | Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19 |
| Details Systematic review and meta-analysis of HCQ prophylaxis RCTs showing a statistically significant reduction in cases for pre-exposure prophylaxis. For PEP trials there were very long treatment delays - in one trial about a third of partici.. |
| PrEP | Karonova et al., Nutrients, doi:10.3390/nu14030505 (Peer Reviewed) | symp. case, ↓94.6%, p=0.002 | Vitamin D Intake May Reduce SARS-CoV-2 Infection Morbidity in Health Care Workers |
| Details Small RCT in Russia with 45 high dose vitamin D patients (50,000IU/wk for 2 wks followed by 5,000IU/day) and 46 low dose patients (2,000IU/day), showing lower cases and lower symptomatic cases with high dose treatment. |
| Levels | Saponaro et al., Frontiers in Immunology, doi:10.3389/fimmu.2021.745713 (Peer Reviewed) | ARDS, ↓36.5%, p=0.43 | Is There a Crucial Link Between Vitamin D Status and Inflammatory Response in Patients With COVID-19? |
| Details Retrospective 93 COVID-19 pneumonia patients in Italy, showing low vitamin D levels associated with severe ARDS, and significantly lower vitamin D levels for non-survivors. |
| Animal | Tatham et al., bioRxiv, doi:10.1101/2022.01.23.477397 (Preprint) | animal study | Lack of Ronapreve (REGN-CoV; casirivimab and imdevimab) virological efficacy against the SARS-CoV 2 Omicron variant (B.1.1.529) in K18-hACE2 mice |
| Details K18-hACE2 mouse study showing that casirivimab/imdevimab was not effective for omicron at doses 2x higher than those effective for previous variants. |
| Early | de Jesús Ascencio-Montiel et al., Archives of Medical Research, doi:10.1016/j.arcmed.2022.01.002 (Peer Reviewed) | death/hosp., ↓59.0%, p<0.0001 | A Multimodal Strategy to Reduce the Risk of Hospitalization/death in Ambulatory Patients with COVID-19 |
| Details Retrospective 28,048 COVID+ patients in Mexico, 7,898 receiving a treatment kit including low dose ivermectin, AZ, aspirin, and acetaminophen, shower lower mortality/hospitalization for those receiving the kit. Delivery of the treatment k.. |
| PrEP | Erden et al., Bratislava Medical Journal, doi:10.4149/BLL_2022_018 (Peer Reviewed) | death, ↑150.0%, p=1.00 | COVID-19 outcomes in patients with antiphospholipid syndrome: a retrospective cohort study |
| Details Retrospective 9 COVID-19 patients with antiphospholipid syndrome in Turkey, showing no significant differences based on existing HCQ treatment. |
| In Vitro | Liu et al., bioRxiv, doi:10.1101/2022.01.20.477147 (Preprint) (In Vitro) | In Vitro | SARS-CoV-2 Viral Genes Compromise Survival and Functions of Human Pluripotent Stem Cell-derived Cardiomyocytes via Reducing Cellular ATP Level |
| Details In Vitro study showing that ivermectin and meclizine may be protective for heart muscle damage due to SARS-CoV-2. |
| Levels | PVSN et al., Biological Trace Element Research, doi:10.1007/s12011-022-03124-7 (Peer Reviewed) | Comparative Analysis of Serum Zinc, Copper and Magnesium Level and Their Relations in Association with Severity and Mortality in SARS-CoV-2 Patients |
| Details Analysis of 150 COVID+ hospitalized patients in India, showing lower zinc levels associated with higher severity. |
| Levels | Ekemen Keleş et al., European Journal of Pediatrics, doi:10.1007/s00431-021-04348-w (Peer Reviewed) | hosp., ↓75.3%, p=0.01 | Serum zinc levels in pediatric patients with COVID-19 |
| Details Prospective study of 100 COVID+ pediatric patients in Turkey, showing significantly increased risk of hospitalization for patients with zinc deficiency. |
| Levels | Juraj et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2022.01.044 (Peer Reviewed) | death, ↓19.0%, p=0.05 | COVID-19 pneumonia patients with 25(OH)D levels lower than 12 ng/ml are at increased risk of death |
| Details Retrospective 357 COVID-19 pneumonia patients in Slovakia, showing higher mortality with vitamin D deficiency (<12ng/mL). All patients received vitamin D supplementation in hospital. In multivariable linear regression, vitamin D levels we.. |
| In Vitro | Goc et al., European Journal of Microbiology and Immunology, doi:10.1556/1886.2021.00022 (Peer Reviewed) (In Vitro) | In Vitro | Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants |
| Details In Vitro study testing combinations of plant extracts and micronutrients with several variants of SARS-CoV-2. A combination of vitamin C, N-acetylcysteine, curcumin, quercetin, resveratrol, theaflavin, naringenin, baicalin, and broccoli e.. |
| In Silico | Parvez et al., arXiv:2201.08176 [q-bio.OT] (Peer Reviewed) | In Silico | Insights from a computational analysis of the SARS-CoV-2 Omicron variant: Host-pathogen interaction, pathogenicity and possible therapeutics |
| Details In Silico analysis of the omicron variant and 10 treatments reported effective for previous variants, predicting that all will be effective for omicron, with ivermectin showing the best results. |
| PrEP | Nguyen et al., Science Advances, doi:10.1126/sciadv.abi6110 (preprint 3/10/2021) (Peer Reviewed) | cases, ↓49.6%, p=0.006 | Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses |
| Details Retrospective 1,212 patients in the USA with a history of seizure-related conditions, showing patients treated with CBD100 had significantly lower incidence of COVID-19 cases compared to a matched control group. In Vitro study showing CB.. |
| PrEP | Usman et al., Journal of Thrombosis and Thrombolysis, doi:10.1007/s11239-022-02631-7 (Peer Reviewed) | death, ↓59.8%, p=0.21 | Metformin use in patients hospitalized with COVID-19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes |
| Details Retrospective 75 diabetes patients, 34 on metformin, showing improved clinical outcomes with treatment, without statistical significance. |
| Late | Zubair et al., Monaldi Archives for Chest Disease, doi:10.4081/monaldi.2022.2062 (Peer Reviewed) | death, ↑8.9%, p=1.00 | The effect of ivermectin on non-severe and severe COVID-19 disease and gender-based difference of its effectiveness |
| Details Retrospective 188 hospitalized patients in Pakistan, 90 treated with ivermectin, showing no significant differences with treatment. The ivermectin group had more severe disease (66% vs 58%, with 6x higher risk for severe disease patients).. |
| Late | Asadirad et al., Phytotherapy Research, doi:10.1002/ptr.7375 (Peer Reviewed) | death, ↓25.9%, p=0.74 | Antiinflammatory potential of nano-curcumin as an alternative therapeutic agent for the treatment of mild-to-moderate hospitalized COVID-19 patients in a placebo-controlled clinical trial |
| Details RCT 60 hospitalized patients in Iran, 30 treated with nano-curcumin, showing significant improvements in inflammatory cytokines, and improvements in clinical outcomes without statistical significance. 240 mg/day nano-curcumin for 7 days. |
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