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Zinc
Zinc for COVID-19: real-time meta analysis of 43 studies
Covid Analysis, August 18, 2022, DRAFT
https://c19zinc.com/meta.html
0 0.5 1 1.5+ All studies 29% 33 35,594 Improvement, Studies, Patients Relative Risk Mortality 27% 16 12,413 Ventilation 51% 5 3,537 ICU admission 22% 5 3,174 Hospitalization 31% 11 5,430 Progression 74% 3 2,558 Recovery 11% 2 299 Cases 32% 5 16,795 Viral clearance 21% 1 115 RCTs 41% 7 1,750 RCT mortality 8% 2 224 Peer-reviewed 24% 29 30,048 Exc. combined 24% 26 31,062 Sufficiency 74% 10 1,116 Prophylaxis 35% 13 21,063 Early 61% 4 3,010 Late 25% 16 11,521 Zinc for COVID-19 c19zinc.com Aug 2022 Favorszinc Favorscontrol after exclusions
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).
Meta analysis using the most serious outcome reported shows 29% [16‑39%] improvement. Results are similar for Randomized Controlled Trials, similar after exclusions, similar for peer-reviewed studies, and similar after excluding studies using combined treatment. Early treatment is more effective than late treatment.
Sufficiency studies, analyzing outcomes based on serum levels, show 74% [60‑84%] improvement for patients with higher zinc levels (10 studies).
Results are robust — in exclusion sensitivity analysis 12 of 33 studies must be excluded to avoid finding statistically significant efficacy in pooled analysis.
0 0.5 1 1.5+ All studies 29% 33 35,594 Improvement, Studies, Patients Relative Risk Mortality 27% 16 12,413 Ventilation 51% 5 3,537 ICU admission 22% 5 3,174 Hospitalization 31% 11 5,430 Progression 74% 3 2,558 Recovery 11% 2 299 Cases 32% 5 16,795 Viral clearance 21% 1 115 RCTs 41% 7 1,750 RCT mortality 8% 2 224 Peer-reviewed 24% 29 30,048 Exc. combined 24% 26 31,062 Sufficiency 74% 10 1,116 Prophylaxis 35% 13 21,063 Early 61% 4 3,010 Late 25% 16 11,521 Zinc for COVID-19 c19zinc.com Aug 2022 Favorszinc Favorscontrol after exclusions
7 studies use combined treatments. When excluding those studies, the pooled improvement is 24% [11‑35%] compared to 29% [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.
While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 9% of zinc studies show zero events in the treatment arm. Multiple treatments are typically used in combination, and other treatments are more effective.
No treatment, vaccine, or intervention is 100% available and effective for all variants. All practical, effective, and safe means should be used. Denying the efficacy of treatments increases mortality, morbidity, collateral damage, and endemic risk.
All data to reproduce this paper and sources are in the appendix. [Tabatabaeizadeh] present another meta analysis for zinc, showing significant improvement for mortality.
Highlights
Zinc reduces risk for COVID-19 with very high confidence for viral clearance and in pooled analysis, high confidence for mortality, ventilation, hospitalization, and progression, and low confidence for cases.
We show traditional outcome specific analyses and combined evidence from all studies, incorporating treatment delay, a primary confounding factor in COVID-19 studies.
Real-time updates and corrections, transparent analysis with all results in the same format, consistent protocol for 43 treatments.
A
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Derwand 79% 0.21 [0.03-1.47] death 1/141 13/377 CT​2 Improvement, RR [CI] Treatment Control Thomas (RCT) -44% 1.44 [0.36-5.71] hosp. 5/58 3/50 Asimi 97% 0.03 [0.00-0.44] ventilation 0/270 9/86 CT​2 Mayberry 53% 0.47 [0.33-0.65] death 938 (n) 1,090 (n) Tau​2 = 0.65, I​2 = 58.1%, p = 0.091 Early treatment 61% 0.39 [0.13-1.16] 6/1,407 25/1,603 61% improvement Carlucci 38% 0.62 [0.46-0.84] death/HPC 54/411 119/521 Improvement, RR [CI] Treatment Control Krishnan 18% 0.82 [0.62-1.09] death 31/58 61/94 Yao 34% 0.66 [0.41-1.07] death 73/196 21/46 Frontera (PSM) 37% 0.63 [0.44-0.91] death 121/1,006 424/2,467 CT​2 Abd-Elsalam (RCT) 1% 0.99 [0.30-3.31] death 5/96 5/95 Rosenthal -16% 1.16 [1.05-1.28] death n/a n/a Darban (RCT) 33% 0.67 [0.14-3.17] progression 2/10 3/10 ICU patients CT​2 Patel (DB RCT) 20% 0.80 [0.15-4.18] death 2/15 3/18 Mulhem 46% 0.54 [0.43-0.68] death 256/1,596 260/1,623 Gadhiya -41% 1.41 [0.69-2.57] death 21/54 34/229 Al Sulaiman (ICU) 36% 0.64 [0.37-1.10] death 23/82 32/82 ICU patients Elavarasi 65% 0.35 [0.24-0.56] death 486 (n) 1,201 (n) Assiri (ICU) -81% 1.81 [0.41-6.97] death 10/60 4/58 ICU patients Kaplan (RCT) -14% 1.14 [0.08-16.6] ventilation 1/14 1/16 CT​2 Zangeneh (ICU) -21% 1.21 [0.51-2.90] death n/a n/a ICU patients Alahmari 30% 0.70 [0.63-0.78] hosp. time 130 (n) 847 (n) Tau​2 = 0.11, I​2 = 87.5%, p = 0.0077 Late treatment 25% 0.75 [0.61-0.93] 599/4,214 967/7,307 25% improvement Louca 1% 0.99 [0.93-1.06] cases Improvement, RR [CI] Treatment Control Mahto 37% 0.63 [0.22-1.49] IgG+ 10/38 83/651 Holt 7% 0.93 [0.59-1.44] cases 21/750 425/14,477 Abdulateef 13% 0.87 [0.38-1.97] hosp. 7/111 23/317 Seet (CLUS. RCT) 50% 0.50 [0.34-0.75] symp. case 33/634 64/619 OT​1 Israel 100% 0.00 [0.00-0.89] hosp. case control CT​2 Bagheri 60% 0.40 [0.04-3.53] progression 33 (n) 477 (n) Gordon 68% 0.32 [0.01-7.87] death 0/104 1/96 Kumar 20% 0.80 [0.21-2.99] death 6/75 3/30 Nimer -25% 1.25 [0.87-1.77] hosp. 41/326 178/1,822 Shehab 47% 0.53 [0.19-1.47] severe case 4/65 22/188 Citu 18% 0.82 [0.12-5.68] severe case 2/74 2/61 CT​2 Stambouli (DB RCT) 68% 0.32 [0.03-2.95] symp. case 1/59 3/56 Tau​2 = 0.25, I​2 = 80.9%, p = 0.027 Prophylaxis 35% 0.65 [0.44-0.95] 125/2,269 804/18,794 35% improvement All studies 29% 0.71 [0.61-0.84] 730/7,890 1,796/27,704 29% improvement 33 zinc COVID-19 studies c19zinc.com Aug 2022 Tau​2 = 0.11, I​2 = 85.6%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors zinc Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Derwand 79% death CT​2 Improvement Relative Risk [CI] Thomas (RCT) -44% hospitalization Asimi 97% ventilation CT​2 Mayberry 53% death Tau​2 = 0.65, I​2 = 58.1%, p = 0.091 Early treatment 61% 61% improvement Carlucci 38% death/hospice Krishnan 18% death Yao 34% death Frontera (PSM) 37% death CT​2 Abd-Elsalam (RCT) 1% death Rosenthal -16% death Darban (RCT) 33% progression ICU patients CT​2 Patel (DB RCT) 20% death Mulhem 46% death Gadhiya -41% death Al Sulaiman (ICU) 36% death ICU patients Elavarasi 65% death Assiri (ICU) -81% death ICU patients Kaplan (RCT) -14% ventilation CT​2 Zangeneh (ICU) -21% death ICU patients Alahmari 30% hospitalization Tau​2 = 0.11, I​2 = 87.5%, p = 0.0077 Late treatment 25% 25% improvement Louca 1% case Mahto 37% IgG positive Holt 7% case Abdulateef 13% hospitalization Seet (CLUS. RCT) 50% symp. case OT​1 Israel 100% hospitalization CT​2 Bagheri 60% progression Gordon 68% death Kumar 20% death Nimer -25% hospitalization Shehab 47% severe case Citu 18% severe case CT​2 Stambouli (DB RCT) 68% symp. case Tau​2 = 0.25, I​2 = 80.9%, p = 0.027 Prophylaxis 35% 35% improvement All studies 29% 29% improvement 33 zinc COVID-19 studies c19zinc.com Aug 2022 Tau​2 = 0.11, I​2 = 85.6%, p < 0.0001 Effect extraction pre-specifiedRotate device for footnotes/details Favors zinc Favors control
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).
Introduction
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.
Figure 2. Treatment stages.
Preclinical Research
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.
Results
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.
0 0.5 1 1.5+ ALL STUDIES MORTALITY VENTILATION ICU ADMISSION HOSPITALIZATION PROGRESSION RECOVERY CASES VIRAL CLEARANCE RANDOMIZED CONTROLLED TRIALS RCT MORTALITY PEER-REVIEWED EXC. COMBINED SUFFICIENCY After Exclusions ALL STUDIES All Prophylaxis Early Late Zinc for COVID-19 C19ZINC.COM AUG 2022
Figure 3. Overview of results.
Treatment timeNumber of studies reporting positive effects Total number of studiesPercentage of studies reporting positive effects Random effects meta-analysis results
Early treatment 3 4 75.0% 61% improvement
RR 0.39 [0.13‑1.16]
p = 0.091
Late treatment 11 16 68.8% 25% improvement
RR 0.75 [0.61‑0.93]
p = 0.0077
Prophylaxis 12 13 92.3% 35% improvement
RR 0.65 [0.44‑0.95]
p = 0.027
All studies 26 33 78.8% 29% improvement
RR 0.71 [0.61‑0.84]
p < 0.0001
Table 1. Results by treatment stage.
Studies Early treatment Late treatment Prophylaxis PatientsAuthors
All studies 3361% [-16‑87%]25% [7‑39%]35% [5‑56%] 35,594 344
With exclusions 2246% [-16‑75%]36% [27‑43%]19% [-9‑40%] 15,453 240
Peer-reviewed 2946% [-16‑75%]18% [-3‑35%]35% [5‑56%] 30,048 289
Randomized Controlled TrialsRCTs 7-44% [-471‑64%]14% [-90‑61%]50% [26‑67%] 1,750 90
Table 2. Results by treatment stage for all studies and with different exclusions.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Derwand 79% 0.21 [0.03-1.47] death 1/141 13/377 CT​2 Improvement, RR [CI] Treatment Control Thomas (RCT) -44% 1.44 [0.36-5.71] hosp. 5/58 3/50 Asimi 97% 0.03 [0.00-0.44] ventilation 0/270 9/86 CT​2 Mayberry 53% 0.47 [0.33-0.65] death 938 (n) 1,090 (n) Tau​2 = 0.65, I​2 = 58.1%, p = 0.091 Early treatment 61% 0.39 [0.13-1.16] 6/1,407 25/1,603 61% improvement Carlucci 38% 0.62 [0.46-0.84] death/HPC 54/411 119/521 Improvement, RR [CI] Treatment Control Krishnan 18% 0.82 [0.62-1.09] death 31/58 61/94 Yao 34% 0.66 [0.41-1.07] death 73/196 21/46 Frontera (PSM) 37% 0.63 [0.44-0.91] death 121/1,006 424/2,467 CT​2 Abd-Elsalam (RCT) 1% 0.99 [0.30-3.31] death 5/96 5/95 Rosenthal -16% 1.16 [1.05-1.28] death n/a n/a Darban (RCT) 33% 0.67 [0.14-3.17] progression 2/10 3/10 ICU patients CT​2 Patel (DB RCT) 20% 0.80 [0.15-4.18] death 2/15 3/18 Mulhem 46% 0.54 [0.43-0.68] death 256/1,596 260/1,623 Gadhiya -41% 1.41 [0.69-2.57] death 21/54 34/229 Al Sulaiman (ICU) 36% 0.64 [0.37-1.10] death 23/82 32/82 ICU patients Elavarasi 65% 0.35 [0.24-0.56] death 486 (n) 1,201 (n) Assiri (ICU) -81% 1.81 [0.41-6.97] death 10/60 4/58 ICU patients Kaplan (RCT) -14% 1.14 [0.08-16.6] ventilation 1/14 1/16 CT​2 Zangeneh (ICU) -21% 1.21 [0.51-2.90] death n/a n/a ICU patients Alahmari 30% 0.70 [0.63-0.78] hosp. time 130 (n) 847 (n) Tau​2 = 0.11, I​2 = 87.5%, p = 0.0077 Late treatment 25% 0.75 [0.61-0.93] 599/4,214 967/7,307 25% improvement Louca 1% 0.99 [0.93-1.06] cases Improvement, RR [CI] Treatment Control Mahto 37% 0.63 [0.22-1.49] IgG+ 10/38 83/651 Holt 7% 0.93 [0.59-1.44] cases 21/750 425/14,477 Abdulateef 13% 0.87 [0.38-1.97] hosp. 7/111 23/317 Seet (CLUS. RCT) 50% 0.50 [0.34-0.75] symp. case 33/634 64/619 OT​1 Israel 100% 0.00 [0.00-0.89] hosp. case control CT​2 Bagheri 60% 0.40 [0.04-3.53] progression 33 (n) 477 (n) Gordon 68% 0.32 [0.01-7.87] death 0/104 1/96 Kumar 20% 0.80 [0.21-2.99] death 6/75 3/30 Nimer -25% 1.25 [0.87-1.77] hosp. 41/326 178/1,822 Shehab 47% 0.53 [0.19-1.47] severe case 4/65 22/188 Citu 18% 0.82 [0.12-5.68] severe case 2/74 2/61 CT​2 Stambouli (DB RCT) 68% 0.32 [0.03-2.95] symp. case 1/59 3/56 Tau​2 = 0.25, I​2 = 80.9%, p = 0.027 Prophylaxis 35% 0.65 [0.44-0.95] 125/2,269 804/18,794 35% improvement All studies 29% 0.71 [0.61-0.84] 730/7,890 1,796/27,704 29% improvement 33 zinc COVID-19 studies c19zinc.com Aug 2022 Tau​2 = 0.11, I​2 = 85.6%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors zinc Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Derwand 79% death CT​2 Improvement Relative Risk [CI] Thomas (RCT) -44% hospitalization Asimi 97% ventilation CT​2 Mayberry 53% death Tau​2 = 0.65, I​2 = 58.1%, p = 0.091 Early treatment 61% 61% improvement Carlucci 38% death/hospice Krishnan 18% death Yao 34% death Frontera (PSM) 37% death CT​2 Abd-Elsalam (RCT) 1% death Rosenthal -16% death Darban (RCT) 33% progression ICU patients CT​2 Patel (DB RCT) 20% death Mulhem 46% death Gadhiya -41% death Al Sulaiman (ICU) 36% death ICU patients Elavarasi 65% death Assiri (ICU) -81% death ICU patients Kaplan (RCT) -14% ventilation CT​2 Zangeneh (ICU) -21% death ICU patients Alahmari 30% hospitalization Tau​2 = 0.11, I​2 = 87.5%, p = 0.0077 Late treatment 25% 25% improvement Louca 1% case Mahto 37% IgG positive Holt 7% case Abdulateef 13% hospitalization Seet (CLUS. RCT) 50% symp. case OT​1 Israel 100% hospitalization CT​2 Bagheri 60% progression Gordon 68% death Kumar 20% death Nimer -25% hospitalization Shehab 47% severe case Citu 18% severe case CT​2 Stambouli (DB RCT) 68% symp. case Tau​2 = 0.25, I​2 = 80.9%, p = 0.027 Prophylaxis 35% 35% improvement All studies 29% 29% improvement 33 zinc COVID-19 studies c19zinc.com Aug 2022 Tau​2 = 0.11, I​2 = 85.6%, p < 0.0001 Effect extraction pre-specifiedRotate device for footnotes/details Favors zinc Favors control
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.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Derwand 79% 0.21 [0.03-1.47] 1/141 13/377 CT​1 Improvement, RR [CI] Treatment Control Mayberry 53% 0.47 [0.33-0.65] 938 (n) 1,090 (n) Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 55% 0.45 [0.33-0.64] 1/1,079 13/1,467 55% improvement Krishnan 18% 0.82 [0.62-1.09] 31/58 61/94 Improvement, RR [CI] Treatment Control Yao 34% 0.66 [0.41-1.07] 73/196 21/46 Frontera (PSM) 37% 0.63 [0.44-0.91] 121/1,006 424/2,467 CT​1 Abd-Elsalam (RCT) 1% 0.99 [0.30-3.31] 5/96 5/95 Rosenthal -16% 1.16 [1.05-1.28] n/a n/a Patel (DB RCT) 20% 0.80 [0.15-4.18] 2/15 3/18 Mulhem 46% 0.54 [0.43-0.68] 256/1,596 260/1,623 Gadhiya -41% 1.41 [0.69-2.57] 21/54 34/229 Al Sulaiman (ICU) 36% 0.64 [0.37-1.10] 23/82 32/82 ICU patients Elavarasi 65% 0.35 [0.24-0.56] 486 (n) 1,201 (n) Assiri (ICU) -81% 1.81 [0.41-6.97] 10/60 4/58 ICU patients Zangeneh (ICU) -21% 1.21 [0.51-2.90] n/a n/a ICU patients Tau​2 = 0.17, I​2 = 89.7%, p = 0.083 Late treatment 22% 0.78 [0.59-1.03] 542/3,649 844/5,913 22% improvement Gordon 68% 0.32 [0.01-7.87] 0/104 1/96 Improvement, RR [CI] Treatment Control Kumar 20% 0.80 [0.21-2.99] 6/75 3/30 Tau​2 = 0.00, I​2 = 0.0%, p = 0.58 Prophylaxis 30% 0.70 [0.21-2.37] 6/179 4/126 30% improvement All studies 27% 0.73 [0.56-0.95] 549/4,907 861/7,506 27% improvement 16 zinc COVID-19 mortality results c19zinc.com Aug 2022 Tau​2 = 0.17, I​2 = 87.6%, p = 0.018 1 CT: study uses combined treatment Favors zinc Favors control
Figure 5. Random effects meta-analysis for mortality results.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Asimi 97% 0.03 [0.00-0.44] 0/270 9/86 CT​1 Improvement, RR [CI] Treatment Control Mayberry 64% 0.36 [0.27-0.47] 938 (n) 1,090 (n) Tau​2 = 2.37, I​2 = 69.2%, p = 0.12 Early treatment 86% 0.14 [0.01-1.66] 0/1,208 9/1,176 86% improvement Carlucci 18% 0.82 [0.54-1.25] 29/411 62/521 Improvement, RR [CI] Treatment Control Abd-Elsalam (RCT) 34% 0.66 [0.19-2.26] 4/96 6/95 Kaplan (RCT) -14% 1.14 [0.08-16.6] 1/14 1/16 CT​1 Tau​2 = 0.00, I​2 = 0.0%, p = 0.29 Late treatment 19% 0.81 [0.54-1.20] 34/521 69/632 19% improvement All studies 51% 0.49 [0.25-0.99] 34/1,729 78/1,808 51% improvement 5 zinc COVID-19 mechanical ventilation results c19zinc.com Aug 2022 Tau​2 = 0.31, I​2 = 73.3%, p = 0.045 1 CT: study uses combined treatment Favors zinc Favors control
Figure 6. Random effects meta-analysis for ventilation.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Mayberry 60% 0.40 [0.31-0.52] 938 (n) 1,090 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 60% 0.40 [0.31-0.52] 0/938 0/1,090 60% improvement Carlucci 23% 0.77 [0.53-1.10] 38/411 82/521 Improvement, RR [CI] Treatment Control Darban (RCT) 6% 0.94 [0.84-1.06] 10 (n) 10 (n) ICU patients CT​1 Al Sulaiman (ICU) -25% 1.25 [0.84-1.87] 82 (n) 82 (n) ICU patients Kaplan (RCT) -14% 1.14 [0.08-16.6] 1/14 1/16 CT​1 Tau​2 = 0.00, I​2 = 5.9%, p = 0.38 Late treatment 6% 0.94 [0.83-1.07] 39/517 83/629 6% improvement All studies 22% 0.78 [0.49-1.22] 39/1,455 83/1,719 22% improvement 5 zinc COVID-19 ICU results c19zinc.com Aug 2022 Tau​2 = 0.20, I​2 = 90.0%, p = 0.28 1 CT: study uses combined treatment Favors zinc Favors control
Figure 7. Random effects meta-analysis for ICU admission.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Derwand 82% 0.18 [0.07-0.54] hosp. 4/141 58/377 CT​1 Improvement, RR [CI] Treatment Control Thomas (RCT) -44% 1.44 [0.36-5.71] hosp. 5/58 3/50 Asimi 99% 0.01 [0.00-0.16] hosp. 0/270 24/86 CT​1 Tau​2 = 2.85, I​2 = 82.7%, p = 0.13 Early treatment 81% 0.19 [0.02-1.62] 9/469 85/513 81% improvement Abd-Elsalam (RCT) 4% 0.96 [0.86-1.08] hosp. time 96 (n) 95 (n) Improvement, RR [CI] Treatment Control Al Sulaiman (ICU) -6% 1.06 [0.85-1.33] hosp. time 82 (n) 82 (n) ICU patients Kaplan (RCT) -14% 1.14 [0.08-16.6] hosp. 1/14 1/16 CT​1 Alahmari 30% 0.70 [0.63-0.78] hosp. time 130 (n) 847 (n) Tau​2 = 0.04, I​2 = 85.8%, p = 0.36 Late treatment 11% 0.89 [0.69-1.14] 1/322 1/1,040 11% improvement Abdulateef 13% 0.87 [0.38-1.97] hosp. 7/111 23/317 Improvement, RR [CI] Treatment Control Israel 100% 0.00 [0.00-0.89] hosp. case control CT​1 Bagheri 41% 0.59 [0.14-1.61] hosp. 4/33 167/477 Nimer -25% 1.25 [0.87-1.77] hosp. 41/326 178/1,822 Tau​2 = 2.48, I​2 = 93.7%, p = 0.054 Prophylaxis 81% 0.19 [0.04-1.03] 52/470 368/2,616 81% improvement All studies 31%