Summary of COVID-19 miscellaneous studies

260 patient NaCl early treatment RCT: 71% lower progression (p<0.0001) and 97% lower severe cases (p<0.0001).
RCT 379 mild COVID-19 cases showing significantly lower prevalence and severity of olfactory and gustatory dysfunction with budesonide nasal spray, chlorhexidine mouthwash, and saline nasal irrigation. The control group received no intervention, the saline group received saline nasal irrigation plus saline nasal spray and mouthwash, and the drug group received saline nasal irrigation plus budesonide nasal spray and chlorhexidine mouthwash. Saline nasal irrigation plus nasal spray and mouthwash were administered once and four times daily, respectively. Both treatment groups had significantly lower prevalence and severity olfactory and gustatory dysfunction. Prevalence was lower for the drug vs. saline group, without statistical significance.
Nov 2023, QJM: An Int. J. Medicine, https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcad262/7439598, https://c19p.org/jingnacl

2. Martin et al., Oral Probenecid for Nonhospitalized Adults with Symptomatic Mild-to-Moderate COVID-19

75 patient probenicid early treatment RCT: 90% improved recovery (p<0.0001) and 36% faster viral clearance (p=0.0001).
RCT 75 outpatients in India with mild to moderate COVID-19 showing faster viral clearance, faster time to symptom resolution, and improvement in disease progression with probenecid treatment for 5 days compared to placebo. Probenecid was well tolerated with only mild adverse events noted. There was a dose-dependent response, with probenecid 1000mg twice daily performing better than 500mg twice daily.
Jul 2023, Viruses, https://www.mdpi.com/1999-4915/15/7/1508, https://c19p.org/martin

3. Holubovska et al., RNA Polymerase Inhibitor Enisamium for Treatment of Moderate COVID-19 Patients: A Randomized, Placebo-Controlled, Multicenter, Double-Blind Phase 3 Clinical Trial

285 patient enisamium late treatment RCT: 86% lower mortality (p=0.25), 75% lower progression (p=0.03), 9% faster improvement (p=0.01), and 89% higher hospital discharge (p=0.12).
RCT 592 hospitalized moderate COVID-19 patients in Ukraine showing improved recovery and lower progression with enisamium. The trial initially included patients with moderate COVID-19 not requiring oxygen, but a mid-trial change was made to exclude this group due to a lack of benefit, and results are reported for the patients requiring oxygen. The greatest benefit was seen in patients treated within 5 days of symptom onset.
May 2024, Advances in Respiratory Medicine, https://www.mdpi.com/2543-6031/92/3/21, https://c19p.org/holubovska

4. Balmforth et al., Evaluating the efficacy and safety of a novel prophylactic nasal spray in the prevention of SARS-CoV-2 infection: A multi-centre, double blind, placebo-controlled, randomised trial.

648 patient xylitol prophylaxis RCT: 47% fewer symptomatic cases (p<0.0001) and 63% lower IgG positivity (p<0.0001).
648 patient RCT pHOXWELL nasal spray in India, showing significantly lower IgGS+ and significantly lower symptomatic cases with treatment. pHOXWELL includes a combination of natural virucidal agents and is designed to mimic the fluid surrounding healthy cells. The spray included xylitol, zinc chloride, polyethylene glycol 400, poloxamer, disodium hydrogen phosphate, sodium chloride, hydroxypropyl methylcellulose, ginger oil, eucalyptus oil, basil oil, clove oil, sodium hydrogen carbonate, potassium dihydrogen phosphate, ethylenediaminetetraacetic acid, sodium hyaluronate, calcium chloride dihydrate, benzalkonium chloride, magnesium chloride hexahydrate, potassium chloride, and glycerol. The spray was administered up to three times per day (TID) 140 μl/nostril for 45 days, with a gap of 6-8 hours between doses.
Jul 2022, J. Clinical Virology, https://www.sciencedirect.com/science/article/pii/S1386653222001809, https://c19p.org/balmforthxy

5. Aghasadeghi et al., Effect of high-dose Spirulina supplementation on hospitalized adults with COVID-19: a randomized controlled trial

189 patient spirulina late treatment RCT: 85% lower mortality (p=0.0002) and 75% higher hospital discharge (p=0.003).
RCT 189 hospitalized COVID-19 patients showing lower mortality and faster recovery with spirulina. Spirulina treatment also resulted in greater reductions in inflammatory markers such as IL-6, TNF-a, IP-10, CRP, ESR, and ferritin. All patients received remdesivir. Spirulina contains many components including calcium spirulan, a sulfated polysaccharide shown to inhibit the replication of various enveloped viruses in vitro, and many nutrients showing benefits for COVID-19 including vitamins A, C, and D, selenium, and zinc.
Apr 2024, Frontiers in Immunology, https://www.frontiersin.org/articles/10.3389/fimmu.2024.1332425/full, https://c19p.org/aghasadeghi

6. Alejandria et al., Virgin Coconut Oil as Adjunctive Therapy for Hospitalized COVID-19 Patients in a Tertiary Referral Hospital: A Randomized Controlled Trial

77 patient VCO late treatment RCT: 86% lower mortality (p=0.12), 86% lower ventilation (p=0.12), 10% shorter hospitalization (p=0.41), and 3% faster recovery (p=0.77).
RCT 77 hospitalized patients showing no significant differences with virgin coconut oil (VCO) treatment.
May 2024, Acta Medica Philippina, https://actamedicaphilippina.upm.edu.ph/index.php/acta/article/view/7498, https://c19p.org/alejandria

7. Khorshiddoust et al., Efficacy of a multiple-indication antiviral herbal drug (Saliravira®) for COVID-19 outpatients: A pre-clinical and randomized clinical trial study

143 patient Saliravira early treatment RCT: 98% lower hospitalization (p<0.0001), 35% faster recovery (p<0.0001), and 63% improved viral clearance.
RCT COVID-19 outpatients showing faster recovery and lower hospitalization with Saliravira, an antiviral drug combining oral tablets, a nasal spray, an oral spray, and inhalation, and containing glycyrrhiza glabra, echinacea purpurea, rheum palmatum, hyssopus officinalis, rosmarinus officinalis, and panax ginseng. Baseline details per group are not provided.
Feb 2022, Biomedicine & Pharmacotherapy, https://www.sciencedirect.com/science/article/pii/S0753332222001172, https://c19p.org/khorshiddoust

8. Butler et al., Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial

1,323 patient azithromycin late treatment RCT: 16% lower need for oxygen therapy (p=0.69), 9% lower hospitalization (p=0.87), and 7% improved recovery (p=0.23).
RCT 1,388 outpatients in the UK showing no significant benefit with azithromycin. There was no significant difference in time to first reported recovery or risk of hospitalization or death by 28 days with azithromycin compared to usual care alone. Only 31% of participants had PCR-confirmed SARS-CoV-2 infection.
Mar 2021, The Lancet, https://www.sciencedirect.com/science/article/pii/S014067362100461X, https://c19p.org/butler4

9. Chen et al., Mitoquinone mesylate as post-exposure prophylaxis against SARS-CoV-2 infection in humans: an exploratory single center pragmatic open label non-randomized pilot clinical trial with matched controls

80 patient Mito-MES prophylaxis study: 91% fewer moderate/severe cases (p=0.05), 83% fewer symptomatic cases (p<0.0001), and 60% fewer cases (p=0.0001).
Open-label non-randomized trial with 80 participants exposed to confirmed SARS-CoV-2 cases, showing lower risk of infection and milder symptoms with mitoquinone mesylate (Mito-MES) prophylaxis. 40 participants took Mito-MES 20mg daily for 14 days, starting within 5 days of exposure, while 40 did not take Mito-MES. 30% of Mito-MES participants tested positive for SARS-CoV-2 compared to 75% of controls. None of the participants who started Mito-MES within 72 hours developed infection, compared to 12 who started on days 3-5. There was no hospitalization in either group.
Mar 2024, eBioMedicine, https://www.sciencedirect.com/science/article/pii/S235239642400077X, https://c19p.org/chen17

10. Sekhavati et al., Safety and effectiveness of azithromycin in patients with COVID-19: An open-label randomised trial

111 patient azithromycin late treatment RCT: 86% lower ventilation (p=0.12), 72% lower ICU admission (p=0.09), and 23% shorter hospitalization (p=0.02).
Randomized controlled trial of 111 hospitalized COVID-19 patients in Iran showing significantly shorter hospital stay, higher oxygen saturation, and lower respiratory rate at discharge with azithromycin plus hydroxychloroquine and lopinavir/ritonavir compared to hydroxychloroquine and lopinavir/ritonavir alone. There were no significant differences in ICU admission, intubation, or mortality, although there was a trend towards lower ICU admission with azithromycin (3.6% vs. 12.7%, p = 0.07). Patients with prior cardiac disease were excluded. The study is limited by the small sample size and open-label design.
Oct 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920303411, https://c19p.org/sekhavati

11. Angeles-Agdeppa et al., Virgin coconut oil (VCO) supplementation relieves symptoms and inflammation among COVID-19 positive adults: a single-blind randomized trial

76 patient VCO late treatment RCT: 47% improved recovery (p=0.13).
RCT 76 hospitalized mild-to-moderate COVID-19 patients in the Philippines showing faster resolution of symptoms with virgin coconut oil (VCO) treatment, without statistical significance.
Jan 2024, J. Nutritional Science, https://www.cambridge.org/core/product/identifier/S2048679023001180/type/journal_article, https://c19p.org/angelesagdeppa

12. Traore et al., Factors of progression to severity and death in COVID-19 patients at two health care sites in Bamako, Mali

azithromycin late treatment study: 69% lower mortality (p=0.04).
Retrospective 1,319 COVID-19 patients in Mali showing lower mortality with azithromycin treatment.
Jan 2025, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-025-10456-x, https://c19p.org/traore

13. Yilgwan et al., Clinical profile and Predictors of Outcomes of Hospitalized Patients with Laboratory-Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 in Nigeria: A Retrospective Analysis of 13 High Burden States in Nigeria

3,462 patient azithromycin late treatment study: 67% lower mortality (p=0.0001).
Retrospective 3,462 hospitalized COVID-19 patients across 13 states in Nigiera, showing lower mortality with AZ. Authors note the worse results with a combination of CQ/HCQ and AZ, compared to either alone, may be related to the side effects becoming more significant for late stage patients.
May 2023, Nigerian Medical J., https://nigerianmedjournal.org/index.php/nmj/article/view/174, https://c19p.org/yilgwanaz

14. Strich et al., Fostamatinib for the Treatment of Hospitalized Adults With Coronavirus Disease 2019: A Randomized Trial

59 patient fostamatinib late treatment RCT: 68% lower mortality (p=0.35).
Double-blind RCT with 59 hospitalized COVID-19 patients requiring oxygen showing that adding fostamatinib to standard of care was safe and resulted in improved clinical outcomes compared to placebo, including faster recovery, fewer days in the ICU, and less supplemental oxygen needed, especially for those with severe or critical disease.
Aug 2021, Clinical Infectious Diseases, https://academic.oup.com/cid/article/75/1/e491/6358811, https://c19p.org/strich

15. Cao et al., A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19

199 patient lopinavir/ritonavir late treatment RCT: 23% lower mortality (p=0.39), 29% greater improvement (p=0.19), and 4% improved viral clearance (p=1).
RCT 199 hospitalized COVID-19 patients showing no significant difference with lopinavir-ritonavir treatment. 28-day mortality was lower in the treatment group, without statistical significance. 3 treatment patients died within 24 hours after randomization and did not receive lopinavir–ritonavir. No significant difference was found in viral RNA load over time between the groups.
May 2020, New England J. Medicine, http://www.nejm.org/doi/10.1056/NEJMoa2001282, https://c19p.org/cao4

16. Gotur et al., Fostamatinib for the Treatment of Hospitalized Patients With COVID-19 Who Required Oxygen Supplementation: Results of a Phase 3 Trial

280 patient fostamatinib late treatment RCT: 47% lower mortality (p=0.17).
RCT 280 hospitalized COVID-19 patients requiring oxygen supplementation, showing significantly fewer days on oxygen (4.8 vs. 7.6), improved 8-point ordinal scale score, and more patients alive and oxygen-free by day 60 with fostamatinib compared to placebo, in addition to standard care. Results are not clear, for example the reported mortality percentages do not match any number of the reported number of patients.
Nov 2023, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/doi/10.1093/ofid/ofad500.004/7448311, https://c19p.org/gotur

17. Tanni et al., Efficacy of BREATHOX® Device Inhalation on Acute Symptoms Associated with COVID-19 (BREATH Study): A Randomized Pilot Clinical Trial

98 patient NaCl early treatment RCT: 75% lower hospitalization (p=0.34) and 10% worse recovery (p=0.7).
RCT 98 outpatients in Brazil, showing faster recovery from cough with inhaled hypertonic saline. Authors note that the effect on coughing may hypothetically be related to a hyperosmotic response influencing the function of different membrane channels and preventing virus entry into the cells; and that the hypertonic solution may increase mucociliary clearance and reduce the destructive inflammatory process in the airways with a decrease in respiratory symptoms.
Sep 2023, J. Clinical Medicine, https://www.mdpi.com/2077-0383/12/18/6075, https://c19p.org/tanni

18. Madamombe et al., Factors associated with COVID-19 fatality among patients admitted in Mashonaland West Province, Zimbabwe 2020-2022: a secondary data analysis

672 patient azithromycin early treatment study: 40% lower mortality (p=0.03).
Retrospective 672 COVID-19 patients in Zimbabwe, showing lower mortality with azithromycin treatment.
Mar 2023, Pan African Medical J., https://www.panafrican-med-journal.com/content/article/44/142/full, https://c19p.org/madamombeaz

19. Piñana et al., Risk factors and outcome of COVID-19 in patients with hematological malignancies

azithromycin prophylaxis study: 58% lower mortality (p=0.02).
Retrospective study of 367 hematology patients with COVID-19 in Spain. Among 216 patients with very severe COVID-19, there was significantly lower mortality with azithromycin treatment. Mortality was also lower with HCQ, but without statistical significance.
Aug 2020, Experimental Hematology & Oncology, https://ehoonline.biomedcentral.com/articles/10.1186/s40164-020-00177-z, https://c19p.org/pinanaaz

20. Lounnas et al., An Independent Analysis of a Retrospective Cohort of 30,423 Covid-19 Patients Treated at IHU-Mediterranean in Marseille, France: Part 1, Efficacy of early Treatment with Hydroxychloroquine and Azithromycin

azithromycin early treatment PSM study: 27% lower combined mortality/ICU admission (p=0.0005).
Independent analysis of the IHU-Mediterranean data [Brouqui] with 30,423 COVID-19 patients showing significantly lower risk of ICU admission or death with early treatment of hydroxychloroquine plus azithromycin (HCQ-AZ), and with azithromycin, both compared to no treatment.
Feb 2024, Archives of Microbiology & Immunology, https://www.fortunejournals.com/articles/an-independent-analysis-of-a-retrospective-cohort-of-30423-covid19-patients-treated-at-ihumediterranean-in-marseille-france-part-1.html, https://c19p.org/lounnas2az

21. Delić et al., Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial

94 patient NaCl ICU RCT: 26% lower mortality (p=0.09).
RCT mechanically ventilated patients in Croatia, showing no significant difference in mortality with saline inhalation. ICU mortality results are from [repozitorij.mefst.unist.hr].
May 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/6/1118, https://c19p.org/delicnacl

22. Shadnoush et al., Effects of Spirulina platensis Supplementation on COVID-19 Severity in Critically Ill Patients: A Randomized Clinical Trial

126 patient spirulina ICU RCT: 3% higher mortality (p=0.93), 26% shorter ICU admission (p=0.007), 17% lower need for oxygen therapy (p=0.64), and 20% shorter hospitalization (p=0.001).
RCT 192 critically ill COVID-19 ICU patients showing reduced SOFA score, hospital stay and ICU stay with spirulina supplementation (5g/day), but no significant difference in mortality, NEWS2 score, APACHE score, NUTRIC score, or respiratory support at discharge.
Sep 2024, J. Cellular and Molecular Anesthesia, https://brieflands.com/articles/jcma-149015, https://c19p.org/shadnoush

23. Cavalcanti et al., Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19

667 patient azithromycin late treatment RCT: 57% lower mortality (p=0.17), 54% higher ventilation (p=0.28), and 18% improved 7-point scale results (p=0.49).
Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot definitively rule out either a substantial benefit of the trial drugs or a substantial harm", sample sizes are too small. The paper uses the terms mild and moderate, however all patients had serious enough disease to be hospitalized, and 14% were actually randomized in the ICU. The trial had significant protocol deviations and unusually low medication adherence. Authors note: "our aim was to exclude patients already receiving longer and potentially therapeutic doses of the study treatments" in explanation for why the study protocol was changed to exclude patients with previous use of the medications >24hrs. Analyzing these patients rather than excluding them may have revealed effectiveness with early use as shown in other studies. The..
Jul 2020, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2019014, https://c19p.org/cavalcantiaz

24. Dugot et al., The Association between Previous Antibiotic Consumption and SARS-CoV-2 Infection: A Population-Based Case-Control Study

156,299 patient azithromycin prophylaxis study: 12% fewer cases (p<0.0001).
Retrospective 31,260 COVID-19 cases and 125,039 matched controls, showing lower risk of COVID-19 with previous azithromycin use.
Mar 2023, Antibiotics, https://www.mdpi.com/2079-6382/12/3/587, https://c19p.org/dugot

25. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments

15,968 patient azithromycin prophylaxis study: 15% lower mortality (p=0.005).
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3az

26. Abaleke et al., Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

7,763 patient azithromycin late treatment RCT: 3% lower mortality (p=0.5), 8% lower ventilation (p=0.29), and 9% higher hospital discharge.
RCT 7,763 hospitalized COVID-19 patients showing no significant differences with very late (75% on oxygen at baseline) azithromycin treatment. Only 91% of treatment patients received azithromycin and 17% of control patients received azithromycin or other macrolides.
Feb 2021, The Lancet, https://www.sciencedirect.com/science/article/pii/S0140673621001495, https://c19p.org/abaleke

27. Mehrizi et al., Drug prescription patterns and their association with mortality and hospitalization duration in COVID-19 patients: insights from big data

917,198 patient azithromycin late treatment study: 32% lower mortality (p<0.0001).
Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehriziaz

28. Dinoi et al., Retrospective Clinical Investigation into the Association Between Abnormal Blood Clotting, Oral Anticoagulant Therapy, and Medium-Term Mortality in a Cohort of COVID-19 Patients

494 patient azithromycin late treatment study: 28% lower mortality (p=0.08).
Retrospective 247 non-survivors and 247 matched survivors in hospitalized COVID-19 patients in Italy showing results for several treatments.
Feb 2025, Biomedicines, https://www.mdpi.com/2227-9059/13/3/535, https://c19p.org/dinoiaz

29. Cegolon et al., Early Negativization of SARS-CoV-2 Infection by Nasal Spray of Seawater plus Additives: The RENAISSANCE Open-Label Controlled Clinical Trial

108 patient xylitol late treatment study: 32% improved viral clearance (p=0.05).
108 patient prospective study showing improved viral clearance with Panthexyl nasal spray (a sterile hypertonic solution containing seawater, xylitol, panthenol and lactic acid).
Nov 2022, Pharmaceutics, https://www.mdpi.com/1999-4923/14/11/2502, https://c19p.org/cegolon

30. Atefi et al., Evaluation of the efficacy and safety of oral N‐acetylcysteine in patients with COVID‐19 receiving the routine antiviral and hydroxychloroquine protocol: A randomized controlled clinical trial

60 patient azithromycin late treatment study: 85% lower mortality (p=0.31).
RCT 60 hospitalized COVID-19 patients evaluating the efficacy and safety of adding oral N-acetylcysteine (NAC) at 600mg three times daily to standard antiviral treatment regimens. There was lower mortality for patients that received azithromycin, without statistical significance.
Nov 2023, Immunity, Inflammation and Disease, https://onlinelibrary.wiley.com/doi/10.1002/iid3.1083, https://c19p.org/atefiaz

31. Donida et al., First COVID-19 wave in the province of Bergamo, Italy: epidemiological and clinical characteristics, outcome and management of the first hospitalized patients

723 patient azithromycin late treatment study: 7% lower mortality (p=0.79).
Retrospective 723 hospitalized COVID-19 patients in Italy showing no significant difference with azithromycin treatment.
Jan 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09034-4, https://c19p.org/donidaaz

32. Yeramaneni et al., Famotidine Use Is Not Associated With 30-day Mortality: A Coarsened Exact Match Study in 7158 Hospitalized Patients With Coronavirus Disease 2019 From a Large Healthcare System

7,158 patient azithromycin late treatment study: 7% lower mortality (p=0.84).
Retrospective 7,158 hospitalized COVID-19 patients in the USA analyzing famotidine treatment, showing no significant difference in mortality with associated azithromycin treatment.
Feb 2021, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)35249-5/fulltext, https://c19p.org/yeramaneniaz

33. Hinks et al., Azithromycin versus standard care in patients with mild-to-moderate COVID-19 (ATOMIC2): an open-label, randomised trial

298 patient azithromycin late treatment RCT: 1% lower combined mortality/hospitalization (p=0.99) and 80% lower progression (p=0.24).
RCT 298 mild-to-moderate COVID-19 outpatients in the UK showing no significant difference in hospitalization or death with late azithromycin treatment. Treatment was delayed an average of 6 days from onset. 7 vs. 3 hospitalizations occurred by day 1 in the treatment vs. control groups in this open label trial (Figure 2).
Oct 2021, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260021002630, https://c19p.org/hinks

34. Chalageri et al., Impact of steam inhalation, saline gargling, and povidone-iodine gargling on clinical outcome of COVID-19 patients in Bengaluru, Karnataka: A randomized control trial

40 patient NaCl early treatment RCT: 43% improved recovery (p=0.0004).
RCT with 20 saline and 20 control low risk patients in India, showing faster recovery with saline gargling, but no significant difference in viral clearance.
Jul 2022, Indian J. Community Medicine, https://journals.lww.com/ijcm/Fulltext/2022/47020/Impact_of_Steam_Inhalation,_Saline_Gargling,_and.12.aspx, https://c19p.org/chalagerisa

35. SOLIDARITY Trial Consortium et al., Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results

2,771 patient lopinavir/ritonavir late treatment RCT: no change in mortality (p=1) and 2% higher ventilation (p=0.89).
WHO SOLIDARITY open-label RCT showing no significant difference in outcomes with lopinavir/ritonavir treatment.
Oct 2020, SOLIDARITY Trial Consortium, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2023184, https://c19p.org/solidaritylpv

36. Talaschian et al., Tocilizumab Failed to Reduce Mortality in Severe COVID-19 Patients: Results from a Randomized Controlled Clinical Trial

36 patient tocilizumab late treatment RCT: 40% higher mortality (p=0.71), 47% higher hospital discharge (p=0.26), and 40% worse recovery (p=0.71).
RCT 40 hospitalized COVID-19 patients in Iran showing no significant improvement in mortality, clinical outcomes, or oxygen therapy requirements with tocilizumab treatment. The study found no significant differences between the tocilizumab and standard of care groups in the number of patients who recovered (70.6% vs. 78.9%), hospitalization duration, or time to clinical improvement.
Feb 2024, Iranian J. Allergy, Asthma and Immunology, https://publish.kne-publishing.com/index.php/IJAAI/article/view/14956, https://c19p.org/talaschian

37. Kuderer et al., Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study

928 patient azithromycin late treatment study: 27% higher mortality (p=0.46).
Retrospective 928 cancer patients, showing higher mortality with HCQ+AZ. The relative risks of different treatments suggest significant confounding by indication. Authors note that HCQ+AZ might not be the cause of increased mortality, but instead was given to patients with more severe COVID-19.
May 2020, Lancet, June 20, 2020, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31187-9/fulltext, https://c19p.org/kudereraz

38. Azimi Pirsaraei et al., Anticoagulant Use in COVID-19 Patients: A Longitudinal Study From Zanjan, Iran

831 patient lopinavir/ritonavir late treatment study: 163% higher mortality (p<0.0001).
Retrospective 831 hospitalized COVID-19 patients showing higher mortality with lopinavir/ritonavir treatment in unadjusted results.
Aug 2024, Cureus, https://www.cureus.com/articles/263779-anticoagulant-use-in-covid-19-patients-a-longitudinal-study-from-zanjan-iran, https://c19p.org/azimipirsaraeilpv

39. Furtado et al., Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial

397 patient azithromycin late treatment RCT: 8% higher mortality (p=0.63) and 30% improvement (p=0.08).
Small RCT comparing the addition of AZ for very late stage patients on ventilation or oxygen. One notable result is that even within this extremely late stage population, results suggest increased efficacy with the addition of AZ for patients with earlier use of AZ/HCQ, OR 0.71 [0.25-2.03] (Figure S4). Patients received 8g of HCQ over 10 days, approaching the high levels used in the RECOVERY trial (9.2g over 10 days), showing significantly more adverse events than typical trials. 50% of patients were on mechanical ventilation at baseline. More than the increase in mortality at day 29 occurred on day 0, and more than 3x the increase occurred by day 2.
Sep 2020, The Lancet, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31862-6/fulltext, https://c19p.org/furtadoaz

40. Soff et al., Association of glycemic control with Long COVID in patients with type 2 diabetes: findings from the National COVID Cohort Collaborative (N3C)

7,430 patient insulin prophylaxis study: 28% higher PASC (p=0.001).
Retrospective 7,430 COVID-positive patients with type 2 diabetes showing lower risk of long COVID or death with metformin use, and higher risk with insulin use.
Feb 2025, BMJ Open Diabetes Research & Care, https://drc.bmj.com/lookup/doi/10.1136/bmjdrc-2024-004536, https://c19p.org/soffins

41. Matviichuk et al., Unveiling risk factors for post-COVID-19 syndrome development in people with type 2 diabetes

469 patient insulin prophylaxis study: 43% higher PASC (p=0.003).
Retrospective 469 patients with type 2 diabetes in Ukraine showing no significant difference in post-COVID-19 syndrome (PCS) with metformin. There was higher risk with Insulin analogs, but lower risk with human insulin.
Dec 2024, Frontiers in Endocrinology, https://www.frontiersin.org/articles/10.3389/fendo.2024.1459171/full, https://c19p.org/matviichukins

42. AlQadheeb et al., Impact of common comorbidities on antimicrobial consumption and mortality amongst critically ill COVID-19 patients: A retrospective two center study in Saudi Arabia

848 patient azithromycin ICU study: 22% higher mortality (p=0.08).
Retrospective 848 ICU patients in Saudi Arabia, showing higher mortality with azithromycin in unadjusted results.
May 2023, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S2590170223000122, https://c19p.org/alqadheebaz

43. Değirmenci et al., Is vitamin D level important in pregnant women with COVID-19?

125 patient lopinavir/ritonavir late treatment study: 136% higher hospitalization (p=0.43).
Retrospective 125 pregnant women hospitalized with COVID-19 in Turkey, showing no significant difference in hospitalization length with HCQ, and longer hospitalization with lopinavir/ritonavir use.
Jul 2024, J. Controversies in Obstetrics & Gynecology and Pediatrics, http://journal-jcogp.com/Publication/DisplayArticle/27358, https://c19p.org/degirmencihlpv

44. Bhat et al., Effectiveness of Dexamethasone for COVID-19 in Hospitalized Patients With Diabetes: A Retrospective Cohort Study

1,058 patient dexamethasone late treatment PSM study: 35% higher mortality (p=0.2) and 46% worse improvement (p=0.02).
Retrospective propensity score matched study of 529 hospitalized diabetic COVID-19 patients showing no significant difference in mortality or clinical improvement with dexamethasone treatment.
Oct 2024, The J. Clinical Endocrinology & Metabolism, https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgae734/7825467, https://c19p.org/bhat2

45. Huh et al., Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea

44,046 patient azithromycin prophylaxis study: 54% higher progression (p=0.33) and 42% fewer cases (p=0.1).
Retrospective database analysis showing no significant differences with azithromycin use.
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2az

46. Omrani et al., Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19

304 patient azithromycin early treatment RCT: 33% higher hospitalization (p=1), 67% lower progression (p=0.62), 100% worse recovery (p=0.5), and 4% worse viral clearance (p=0.63).
Low risk patient RCT for HCQ+AZ and HCQ vs. control, not showing any significant differences. Authors note that the results are not applicable to higher risk patients, that positive PCR may simply reflect detection of inactive (non-infectious) viral remnants, that an alternative dosage regimen may be more effective, and that medication adherence was unknown. HCQ dosing was 600mg/day for 1 week, therapeutic levels may not be reached for several days. There were no deaths or serious adverse events. Viral load was already very high at baseline.
Nov 2020, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537020303898, https://c19p.org/omraniaz

47. Nowak et al., COVID-19 among Kidney Transplant Recipients: Evaluating Risk Factors During the Initial Phase of the Pandemic

5,824 patient insulin prophylaxis study: 84% higher combined mortality/hospitalization (p=0.004).
Retrospective 5,824 kidney transplant recipients in Sweden showing proton pump inhibitor use associated with higher risk of severe COVID-19.
Jan 2025, Clinical Kidney J., https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfaf030/7989457, https://c19p.org/nowakins

48. Dinoi et al., Retrospective Clinical Investigation into the Association Between Abnormal Blood Clotting, Oral Anticoagulant Therapy, and Medium-Term Mortality in a Cohort of COVID-19 Patients

494 patient insulin late treatment study: 55% higher mortality (p=0.02).
Retrospective 247 non-survivors and 247 matched survivors in hospitalized COVID-19 patients in Italy showing results for several treatments.
Feb 2025, Biomedicines, https://www.mdpi.com/2227-9059/13/3/535, https://c19p.org/dinoiins

49. He et al., Clinical characteristics and risk factors for in-hospital mortality of COVID-19 patients in Hubei Province: A multicenter retrospective study

53,030 patient insulin late treatment study: 235% higher mortality (p<0.0001).
Retrospective 53,030 COVID-19 patients from 138 hospitals in Hubei, China showing lower mortality with metformin.
Nov 2024, IJC Heart & Vasculature, https://www.sciencedirect.com/science/article/pii/S2352906724002409, https://c19p.org/he2ins

50. Yen et al., Predictors for cause-specific and timing of deaths in patients with COVID-19: a cohort study in Taiwan

2,196 patient dexamethasone early treatment study: 103% higher mortality (p=0.0002).
Retrospective 2,196 COVID-19 patients in Taiwan (49% mild cases, 44% moderate, 7% severe) showing significantly higher mortality with dexamethasone. Authors report that all infected patients were hospitalized at the time of the study in Taiwan.
Aug 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09654-w, https://c19p.org/yen2dex

51. Yen et al., Predictors for cause-specific and timing of deaths in patients with COVID-19: a cohort study in Taiwan

2,196 patient tocilizumab early treatment study: 58% higher mortality (p=0.06).
Retrospective 2,196 COVID-19 patients in Taiwan (49% mild cases, 44% moderate, 7% severe) showing higher mortality with tocilizumab, without statistical significance. Authors report that all infected patients were hospitalized at the time of the study in Taiwan.
Aug 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09654-w, https://c19p.org/yen2tz

52. Ho et al., A Retrospective Cohort Study Assessing the Impact of Statin Therapy on Hospital Length of Stay and Inpatient Mortality in COVID-19 Patients

26,445 patient tocilizumab late treatment study: 290% higher mortality (p<0.0001).
Retrospective 26,445 hospitalized COVID-19 patients in the USA, showing higher mortality with tocilizumab.
Oct 2023, HCA Healthcare J. Medicine, https://scholarlycommons.hcahealthcare.com/hcahealthcarejournal/vol4/iss5/5, https://c19p.org/ho3tz

53. Madamombe et al., Factors associated with COVID-19 fatality among patients admitted in Mashonaland West Province, Zimbabwe 2020-2022: a secondary data analysis

672 patient dexamethasone early treatment study: 130% higher mortality (p<0.0001).
Retrospective 672 COVID-19 patients in Zimbabwe, showing higher mortality with dexamethasone treatment.
Mar 2023, Pan African Medical J., https://www.panafrican-med-journal.com/content/article/44/142/full, https://c19p.org/madamombedx

54. Reis et al., Effect of spirulina on risk of hospitalization among patients with COVID-19: the TOGETHER randomized trial

1,126 patient spirulina early treatment RCT: 21% higher progression (p=0.29).
RCT 1,126 patients in Brazil showing no significant differences with low dose spirulina. The dose used was 7.6 times lower than the dose used by [Aghasadeghi] which shows significantly lower mortality. eFigure 1 shows 12 events in the treatment group before the first event in the placebo group. The probability of this happening is very low, ~ 0.001. One possible cause would be if some process resulted in patients expected to visit the ER soon being more likely to be placed in the treatment group. (Another possibility is treatment side effects causing ER visits, however the were fewer adverse events and fewer severe adverse events in the treatment group).
Aug 2024, The American J. Clinical Nutrition, https://www.sciencedirect.com/science/article/pii/S0002916524005884, https://c19p.org/reis13

55. Garneau et al., Clinical effects of dexamethasone among patients with sickle cell disease hospitalized with COVID-19: Outcomes from a single academic health system

30 patient dexamethasone late treatment study: 423% higher ICU admission (p=0.14) and 155% longer hospitalization (p=0.06).
Retrospective 30 hospitalized patients with sickle cell disease (SCD) showing increased risk of venous thromboembolism (VTE) with dexamethasone treatment for COVID-19. There were also trends towards increased ICU admission and longer hospital stays with dexamethasone, without statistical significance.
Nov 2024, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0313289, https://c19p.org/garneau

56. Collins et al., Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia

400 patient fostamatinib late treatment RCT: 44% higher mortality (p=0.31) and 39% worse 7-point scale results (p=0.09).
RCT 400 hospitalized COVID-19 patients with hypoxemia showing no significant benefit with fostamatinib compared to placebo. There was no significant difference in the primary outcome of oxygen-free days (mean 13.4 vs. 14.2 days, AOR 0.82) or 28-day mortality (11.3% vs. 8.1%, AOR 1.44). Fostamatinib was associated with a higher incidence of elevated aspartate aminotransferase (11.6% vs. 5.5%, AOR 2.28).
Dec 2024, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2827330, https://c19p.org/collins

57. Horby et al., Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

5,040 patient lopinavir/ritonavir late treatment RCT: 3% higher mortality (p=0.6), 15% higher ventilation (p=0.15), and 2% lower hospital discharge (p=0.53).
RCT with 1,616 hospitalized COVID-19 patients showing no significant differences with lopinavir-ritonavir treatment compared to usual care.
Oct 2020, The Lancet, https://www.sciencedirect.com/science/article/pii/S0140673620320134, https://c19p.org/horby2

58. Oldenburg et al., Effect of Oral Azithromycin vs Placebo on COVID-19 Symptoms in Outpatients With SARS-CoV-2 Infection

800 patient azithromycin late treatment RCT: 788% higher hospitalization (p=0.16), 418% worse results (p=0.01), 1% improved recovery (p=1), and 12% lower transmission (p=0.66).
RCT 263 COVID-19 outpatients showing no significant difference in COVID-19 symptoms at day 14 with a single 1.2g dose of azithromycin vs placebo. Treatment was very late, a median of 7 days after symptom onset (3 days from onset to test results, 3 days to enrollment, 1 day for shipping).
Aug 2021, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2782166, https://c19p.org/oldenburg

59. Franco-Moreno et al., Effect of early administration of dexamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome: EARLY-DEX COVID-19 trial

126 patient dexamethasone late treatment RCT: 134% higher ventilation (p=0.41), 217% higher ICU admission (p=0.46), 17% higher ARDS (p=0.81), and 3% shorter hospitalization (p=0.88).
RCT 126 hospitalized COVID-19 pneumonia patients not requiring oxygen at admission, showing no significant difference in outcomes with dexamethasone treatment.
Jul 2024, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2024.1385833/full, https://c19p.org/francomoreno

60. Franco-Moreno et al., Effect of early administration of dexamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome: EARLY-DEX COVID-19 trial

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