•Statistically significant improvements are seen for mortality, ventilation, hospitalization, progression, and viral clearance. 13 studies from 13 independent teams in 7 different countries show statistically significant
improvements in isolation (9 for the most serious outcome).
•Sufficiency studies, analyzing outcomes based on serum levels,
show 74% [64‑82%] improvement for patients with higher zinc levels
(11 studies).
•Results are robust — in exclusion sensitivity analysis 12 of 34
studies must be excluded to avoid finding statistically significant efficacy
in pooled analysis.
•7 studies use combined treatments.
When excluding those studies, the pooled improvement is 24% [12‑35%] compared
to 28% [16‑39%].
•Early treatment results are dominated by [Thomas], however this
study used a low dose and was conducted in a location with low levels of zinc
deficiency.
•No treatment, vaccine, or
intervention is 100% effective and available. All practical, effective, and
safe means should be used based on risk/benefit analysis.
Multiple treatments are typically used
in combination, and other treatments
are more effective.
Only 9% of zinc
studies show zero events with treatment.
The quality of non-prescription supplements can vary widely [Crawford, Crighton].
•All data to reproduce this paper and
sources are in the appendix.
[Tabatabaeizadeh] present another meta analysis for zinc, showing significant improvement for mortality.
We show traditional outcome specific analyses and combined
evidence from all studies, incorporating treatment delay, a primary
confounding factor in COVID-19 studies.
Figure 1.A. Random effects
meta-analysis. This plot shows pooled effects, discussion can be found in the heterogeneity section,
and results for specific outcomes can be found in the individual outcome analyses.
Effect extraction is pre-specified, using the most serious outcome reported.
For details of effect extraction see the appendix.
B. Scatter plot showing the
distribution of effects reported in studies. C. History of all reported
effects (chronological within treatment stages).
We analyze all significant studies
concerning the use of
zinc
for COVID-19.
Search methods, inclusion criteria, effect
extraction criteria (more serious outcomes have priority), all individual
study data, PRISMA answers, and statistical methods are detailed in
Appendix 1. We present random effects meta-analysis results for all
studies, for studies within each treatment stage, for individual outcomes, for
peer-reviewed studies, for Randomized Controlled Trials (RCTs), and after
exclusions.
Figure 2 shows stages of possible treatment for
COVID-19. Prophylaxis refers to regularly taking medication before
becoming sick, in order to prevent or minimize infection. Early
Treatment refers to treatment immediately or soon after symptoms appear,
while Late Treatment refers to more delayed treatment.
An In Silico study supports the efficacy of zinc [Pormohammad].
2 In Vitro studies support the efficacy of zinc [Hajdrik, Panchariya].
Preclinical research is an important part of the development of
treatments, however results may be very different in clinical trials.
Preclinical results are not used in this paper.
Figure 3 shows a visual overview of the results, with details in
Table 1 and Table 2.
Figure 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15
show forest plots for a random effects meta-analysis of
all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, progression, recovery, cases, viral clearance, sufficiency studies, peer reviewed studies, and all studies excluding combined treatment studies.
Figure 4. Random effects meta-analysis for all studies with pooled effects.
This plot shows pooled effects, discussion can be found in the heterogeneity section,
and results for specific outcomes can be found in the individual outcome analyses.
Effect extraction is pre-specified, using the most serious outcome reported.
For details of effect extraction see the appendix.
