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Factors Influencing Disease Stability and Response to Tocilizumab Therapy in Severe COVID-19: A Retrospective Cohort Study

Hafez et al., Antibiotics, doi:10.3390/antibiotics11081078

Aug 2022

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Vitamin D for COVID-19

8th treatment shown to reduce risk in October 2020

^*, now known with p < 0.00000000001 from 120 studies, recognized in 8 countries.

Lower risk for mortality, ICU admission, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,000+ studies for 60+ treatments. c19early.org

Retrospective 49 severe COVID-19 patients treated with tocilizumab, showing lower mortality with vitamin D treatment and a dose-dependent response.

Cholecalciferol was used in this study. Meta analysis shows that late stage treatment with calcitriol / calcifediol (or paricalcitol, alfacalcidol, etc.) is more effective than cholecalciferol: 65% [41‑79%] lower risk vs. 39% [26‑49%] lower risk. Cholecalciferol requires two hydroxylation steps to become activated - first in the liver to calcifediol, then in the kidney to calcitriol. Calcitriol, paricalcitol, and alfacalcidol are active vitamin D analogs that do not require conversion. This allows them to have more rapid onset of action compared to cholecalciferol. The time delay for cholecalciferol to increase serum calcifediol levels can be 2-3 days, and the delay for converting calcifediol to active calcitriol can be up to 7 days.

This is the 93rd of 120 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 248 sextillion).

29 studies are RCTs, which show efficacy with p=0.0000024.

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risk of death, 93.7% lower, RR 0.06, p = 0.07, treatment 0 of 7 (0.0%), control 12 of 30 (40.0%), NNT 2.5, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), high dose, 50,000IU every other day for two weeks or one intramuscular shot of 300,000IU.

risk of death, 58.3% lower, RR 0.42, p = 0.28, treatment 2 of 12 (16.7%), control 12 of 30 (40.0%), NNT 4.3, low dose, ≤10,000IU/day.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Hafez et al., 9 Aug 2022, retrospective, Egypt, peer-reviewed, 2 authors, study period April 2020 - June 2020, dosage 50,000IU days 1, 3, 5, 7, 9, 11, 13, 50,000IU every other day for two weeks or one intramuscular shot of 300,000IU. Contact: wael.hafez@nmc.ae (corresponding author).

This Paper Vitamin D All

Factors Influencing Disease Stability and Response to Tocilizumab Therapy in Severe COVID-19: A Retrospective Cohort Study

Wael Hafez, Ahmed Abdelrahman

Antibiotics, doi:10.3390/antibiotics11081078

1) Background: The efficacy of tocilizumab in COVID-19 has been doubted. The study aimed to investigate factors affecting disease stability and response to tocilizumab among severe COVID-19 patients. (2) Methods: This was a cohort study of 70 severe COVID-19 patients at NMC Royal Hospital, UAE, from April to June 2020. (3) Results: Elderly patients and those with cardiovascular comorbidities had a higher risk of unstable COVID-19 (p = 0.025). Regarding tocilizumab therapy timing, compared to the critical group receiving tocilizumab, the unstable severe patients receiving tocilizumab had a significantly higher rate of improvement (86%). In contrast, the late critical subgroup showed a significantly increased mortality rate (52.9%). The risk for secondary infection and adverse events following tocilizumab was higher in the late critical group than in the unstable severe and early critical groups (p = 0.024 and p = 0.006, respectively). Therapeutic doses of anticoagulation and high-dose vitamin D were correlated with better outcomes than the prophylactic dose and the treatment dose of vitamin D (p < 0.001 and p = 0.07, respectively). (4) Conclusions: elderly patients and those with cardiovascular disease developed unstable COVID-19. Tocilizumab is a potentially effective choice against severe and critical COVID-19. Early tocilizumab administration combined with therapeutic dose anticoagulation and high vitamin D doses could improve the patients' outcomes.

Informed Consent Statement: This was a retrospective study; all Patients Identifiers were removed during the data collection process, with complete protection of patients' privacy. The study followed the Helsinki Declaration in terms of patient privacy. The Regional Research Ethics Committee, Department of Health, Abu Dhabi, UAE, reviewed and approved the study (Ref: ADHRTC-2021-178). As a retrospective study, informed consent was not required. Conflicts of Interest: All authors declare no conflict of interest.

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Late treatment
is less effective

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