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Introduction
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Appendix 1. Methods and Study..
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Treatment RCTs
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Cholecalciferol studies
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Vitamin D for COVID-19: real-time meta analysis of 128 studies
https://vdmeta.com/
00.250.50.7511.251.51.752+All studies40%4750,837Improvement, Studies, PatientsRelative Risk, 95% CIWith exclusions44%4149,222Mortality51%2912,401Ventilation33%102,823ICU admission53%133,976Hospitalization17%1023,855Cases15%921,790RCTs48%8694Peer-reviewed36%4449,587Sufficiency55%8140,421Cholecalciferol32%3842,856Calcifediol61%97,981Prophylaxis20%2446,612Early81%6912Late56%173,313Vitamin D for COVID-19vdmeta.com Oct 22, 2021Favors vitamin DFavors control
87% of 47 vitamin D treatment studies report positive effects (19 statistically significant in isolation).
Random effects meta-analysis with pooled effects using the most serious outcome reported shows 81% [65‑90%] and 40% [32‑47%] improvement for early treatment and for all studies. Results are similar after restriction to 44 peer-reviewed studies: 84% [68‑92%] and 36% [28‑43%], and for the 29 mortality results: 79% [61‑88%] and 51% [34‑63%].
Statistically significant improvements are seen in treatment studies for mortality, ICU admission, hospitalization, and cases.
Late stage treatment with calcifediol/calcitriol shows greater improvement compared to cholecalciferol: 78% [67‑85%] vs. 44% [24‑60%].
Sufficiency studies show a strong association between vitamin D sufficiency and outcomes. Meta analysis of the 81 studies with pooled effects using the most serious outcome reported shows 55% [47‑61%] improvement.
While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 13% of vitamin D treatment studies show zero events in the treatment arm.
Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. All practical, effective, and safe means should be used. Not doing so increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateral damage.
All data to reproduce this paper and the sources are in the appendix.
ImprovementStudies AuthorsPatients
Treatment RCTs 48% [16‑67%] 8 77 694
Treatment studies 40% [32‑47%] 47 443 50,837
Cholecalciferol treatment 32% [23‑40%] 38 332 42,856
Calcifediol/calcitriol treatment 61% [30‑78%] 9 111 7,981
Treatment mortality 51% [34‑63%] 29 268 12,401
Sufficiency studies 55% [47‑61%] 81 657 40,421
    
  
A
00.250.50.7511.251.51.752+Annweiler89%0.11 [0.03-0.48]80,000IUdeath10/575/9Improvement, RR [CI]Dose (5d)TreatmentControlAnnweiler63%0.37 [0.06-2.21]80,000IUdeath3/1610/32Burahee93%0.07 [0.00-1.06]400,000IUdeath0/122/2Loucera (PSM)72%0.28 [0.20-0.39]varies (c)death193 (n)193 (n)Asimi97%0.03 [0.00-0.44]10,000IUventilation0/2709/86CT​1Sánchez-Zuno (RCT)89%0.11 [0.01-1.86]50,000IUsevere case0/224/20Tau​2 = 0.20; I​2 = 41.2%Early treatment81%0.19 [0.10-0.35]13/57030/34281% improvementTan80%0.20 [0.04-0.93]5,000IUoxygen3/1716/26Improvement, RR [CI]Dose (5d)TreatmentControlKrishnan19%0.81 [0.49-1.34]n/adeath8/1684/136Castillo (RCT)85%0.15 [0.01-2.93]0.8mg (c)death0/502/26Rastogi (RCT)53%0.47 [0.24-0.92]300,000IUviral+6/1619/24Murai (DB RCT)-49%1.49 [0.55-4.05]200,000IUdeath9/1196/118Ling80%0.20 [0.08-0.48]40,000IUdeath73 (n)253 (n)Jevalikar82%0.18 [0.02-1.69]60,000IUdeath1/1283/69Giannini37%0.63 [0.35-1.09]400,000IUdeath/ICU14/3629/55Nogués (QR)79%0.21 [0.10-0.43]0.8mg (c)death21/44762/391Lakkireddy (RCT)61%0.39 [0.08-1.91]300,000IUdeath2/445/43Lohia11%0.89 [0.32-1.89]n/adeath26 (n)69 (n)Alcala-Diaz81%0.19 [0.04-0.83]0.8mg (c)death4/7990/458Güven25%0.75 [0.37-1.24]300,000IUdeath43/11330/62Soliman (RCT)63%0.37 [0.09-2.78]200,000IUdeath7/403/16Elamir (RCT)86%0.14 [0.01-2.63]2.5μg (t)death0/253/25Yildiz81%0.19 [0.03-1.37]300,000IUdeath1/3724/170Maghbooli (DB RCT)40%0.60 [0.15-2.38]125μg (c)death3/535/53Tau​2 = 0.26; I​2 = 62.4%Late treatment56%0.44 [0.31-0.62]122/1,319381/1,99456% improvementBlanch-Rubió8%0.92 [0.63-1.36]n/acases62/1,30347/799Improvement, RR [CI]Dose (1m)TreatmentControlHernández-4%1.04 [0.26-4.10]variesdeath2/1920/197Annweiler93%0.07 [0.01-0.61]50,000IUdeath2/2910/32Cereda-73%1.73 [0.81-2.74]variesdeath7/1840/152Louca8%0.92 [0.88-0.97]n/acasespopulation-based cohortCangiano70%0.30 [0.10-0.87]50,000IUdeath3/2039/78Vasheghani30%0.70 [0.33-1.49]n/adeath7/8848/420Ma30%0.70 [0.50-0.97]n/acases49/3631,329/7,934Sulli50%0.50 [0.34-0.73]n/acases22/6643/64Mazziotti19%0.81 [0.45-1.47]variesdeath116 (n)232 (n)Meltzer36%0.64 [0.29-1.41]n/acases6/131239/3,338Ünsal71%0.29 [0.11-0.76]variespneumonia4/2814/28Oristrell43%0.57 [0.41-0.80]7.4μg (t)death2,296 (n)3,407 (n)Levitus31%0.69 [0.37-1.24]variessevere case65 (n)64 (n)Dudley22%0.78 [0.23-2.61]22,400IUsymp. case15/582/6Fasano42%0.58 [0.34-0.99]n/acases13/32992/1,157Oristrell-1%1.01 [0.93-1.09]varies (c)deathpopulation-based cohortJimenez50%0.50 [0.28-0.90]3.7μg (p)death16/9465/191Israel9%0.91 [0.85-0.97]n/ahosp.737/2,4066,216/18,453Mohseni12%0.88 [0.75-1.03]n/acases99/192242/411Sinaci90%0.10 [0.01-1.70]n/asevere case0/367/123Pecina-70%1.70 [0.36-8.20]n/adeath29 (n)63 (n)Bagheri71%0.29 [0.10-0.83]n/aprogression131 (n)379 (n)Arroyo-Díaz-12%1.12 [0.73-1.66]n/adeath50/189167/1,078Tau​2 = 0.02; I​2 = 69.0%Prophylaxis20%0.80 [0.72-0.89]1,094/8,0068,620/38,60620% improvementAll studies40%0.60 [0.53-0.68]1,229/9,8959,031/40,94240% improvementAll 47 vitamin D COVID-19 treatment studiesvdmeta.com Oct 22, 20211 CT: study uses combined treatmentTau​2 = 0.07; I​2 = 81.3%; Z = 7.95Effect extraction pre-specified, see appendixFavors vitamin DFavors control
    
  
B
    
  
C
    
  
D
Figure 1. A. Random effects meta-analysis of treatment studies. This plot shows pooled effects, analysis for individual outcomes is below, and more details on pooled effects can be found in the heterogeneity section. Effect extraction is pre-specified, using the most serious outcome reported. Simplified dosages are shown for comparison, these are the total dose in the first five days for treatment, and the monthly dose for prophylaxis. Calcifediol, calcitriol, and paricalcitol treatment are indicated with (c), (t), and (p). For details of effect extraction and full dosage information see the appendix. B. Scatter plot showing the distribution of effects reported in serum level analysis (sufficiency) studies and treatment studies (the vertical lines and shaded boxes show the median and interquartile range). C and D. Chronological history of all reported effects for treatment studies and sufficiency studies.
Introduction
We analyze all significant studies regarding vitamin D and 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 studies analyzing outcomes based on sufficiency, for all treatment studies, for mortality results only, and for treatment studies within each treatment stage.
Vitamin D.
Vitamin D undergoes two conversion steps before reaching the biologically active form as shown in Figure 2. The first step is conversion to calcidiol, or 25(OH)D, in the liver. The second is conversion to calcitriol, or 1,25(OH)2D, which occurs in the kidneys, the immune system, and elsewhere. Calcitriol is the active, steroid-hormone form of vitamin D, which binds with vitamin D receptors found in most cells in the body. Vitamin D was first identified in relation to bone health, but is now known to have multiple functions, including an important role in the immune system [Carlberg, Martens]. For example, [Quraishi] show a strong association between pre-operative vitamin D levels and hospital-acquired infections, as shown in Figure 3. There is a significant delay involved in the conversion from cholecalciferol, therefore calcifediol (calcidiol) or calcitriol may be preferable for treatment.
Figure 2. Simplified view of vitamin D sources and conversion.
Figure 3. Risk of hospital-acquired infections as a function of pre-operative vitamin D levels, from [Quraishi].
Sufficiency.
Many vitamin D studies analyze outcomes based on serum vitamin D levels which may be maintained via sun exposure, diet, or supplementation. We refer to these studies as sufficiency studies, as they typically present outcomes based on vitamin D sufficiency. These studies do not establish a causal link between vitamin D and outcomes. In general, low vitamin D levels are correlated with many other factors that may influence COVID-19 susceptibility and severity. Therefore, beneficial effects found in these studies may be due to factors other than vitamin D. On the other hand, if vitamin D is causally linked to the observed benefits, it is possible that adjustments for correlated factors could obscure this relationship. COVID-19 disease may also affect vitamin D levels [Silva], suggesting additional caution in interpreting results for studies where the vitamin D levels are measured during the disease. For these reasons, we analyze sufficiency studies separately from treatment studies. We include all sufficiency studies that provide a comparison between two groups with low and high levels. A few studies only provide results as a function of change in vitamin D levels [Butler-Laporte, Raisi-Estabragh], which may not be indicative of results for deficiency/insufficiency versus sufficiency (increasing already sufficient levels may be less useful for example). A few studies show the average vitamin D level for patients in different groups [Al-Daghri, Chodick, D'Avolio, Kerget, Mardani, Vassiliou], all of which show lower D levels for worse outcomes. Other studies analyze vitamin D status and outcomes in geographic regions [Jayawardena, Marik, Papadimitriou, Rafailia, Rhodes, Sooriyaarachchi, Walrand, Yadav], all finding worse outcomes to be more likely with lower D levels.
Treatment.
For studies regarding treatment with vitamin D, we distinguish three stages as shown in Figure 4. Prophylaxis refers to regularly taking vitamin D before being infected in order to minimize the severity of infection. Due to the mechanism of action, vitamin D is unlikely to completely prevent infection, although it may prevent infection from reaching a level detectable by PCR. Early Treatment refers to treatment immediately or soon after symptoms appear, while Late Treatment refers to more delayed treatment.
Figure 4. Treatment stages.
Results
Figure 1 shows the effects reported in sufficiency studies and treatment studies. Figure 5 and 6 show results by treatment stage. Figure 7 shows a forest plot for random effects meta-analysis of sufficiency studies, while Figure 8, 9, 10, 11, 12, 13, 14, 15, 16, and 17 show forest plots for all treatment studies with pooled effects, RCT studies, calcifediol/calcitriol studies, cholecalciferol studies, and for studies reporting mortality, mechanical ventilation, ICU admission, hospitalization, and case results only. Table 1 summarizes the results.
Study typeNumber of studies reporting positive results Total number of studiesPercentage of studies reporting positive results Random effects meta-analysis results
Analysis of outcomes based on sufficiency 75 81 92.6% 55% improvement
RR 0.45 [0.39‑0.53]
p < 0.0001
Early treatment 6 6 100% 81% improvement
RR 0.19 [0.10‑0.35]
p < 0.0001
Late treatment 16 17 94.1% 56% improvement
RR 0.44 [0.31‑0.62]
p < 0.0001
Prophylaxis 19 24 79.2% 20% improvement
RR 0.80 [0.72‑0.89]
p < 0.0001
All treatment studies 41 47 87.2% 40% improvement
RR 0.60 [0.53‑0.68]
p < 0.0001
Table 1. Results.
    
  
Figure 5. Results by treatment stage.
    
  
Figure 6. Results by treatment stage.
    
  
00.250.50.7511.251.51.752+Lau45%0.55 [0.18-1.68]ICU2/511/15Improvement, RR [CI]TreatmentControlMendy7%0.93 [0.33-2.47]death21/6005/89Panagiotou52%0.48 [0.24-0.95]ICU8/4434/90Faul69%0.31 [0.10-0.95]ventilation4/218/12Merzon46%0.54 [0.23-1.02]hosp.79 (n)703 (n)Carpagnano71%0.29 [0.10-0.85]death5/344/8Im73%0.27 [0.11-0.64]cases98 (n)102 (n)Hastie17%0.83 [0.57-1.20]deathpopulation-based cohortBaktash29%0.71 [0.18-2.78]death4/316/39Meltzer44%0.56 [0.36-0.89]cases39/31732/172Israel21%0.79 [0.75-0.84]casespopulation-based cohortRadujkovic93%0.07 [0.01-0.34]death144 (n)12 (n)Kaufman53%0.47 [0.30-0.74]casespopulation-based cohortMaghbooli52%0.48 [0.22-1.05]death7/7227/134Karahan83%0.17 [0.08-0.41]death5/4664/103Yılmaz73%0.27 [0.01-5.14]severe case0/112/29Faniyi29%0.71 [0.59-0.86]seropositive170/33144/61Ye93%0.07 [0.01-0.81]hosp.2/368/26Macaya55%0.45 [0.15-1.06]severe case11/3520/45Tomasa-Irriguible35%0.65 [0.31-1.24]ventilation15/2718/78Hernández83%0.17 [0.07-0.41]death/ICU35 (n)162 (n)Abrishami76%0.24 [0.06-0.93]death3/479/26Cereda-120%2.20 [1.01-3.22]death10/3024/99Walk-0%1.00 [0.60-1.67]int./death48/11010/23Luo63%0.37 [0.17-0.81]progression335 (n)560 (n)Jain85%0.15 [0.04-0.61]death2/6419/90De Smet70%0.30 [0.10-0.80]death7/7720/109Katz78%0.22 [0.17-0.27]casespopulation-based cohortAlguwaihes86%0.14 [0.04-0.59]death111 (n)328 (n)Vassiliou91%0.09 [0.01-1.51]death0/155/15Abdollahi54%0.46 [0.29-0.73]cases108 (n)294 (n)Szeto-6%1.06 [0.49-2.26]death14/588/35Karonova79%0.21 [0.03-1.28]death1/2312/57Amin-32%1.32 [0.88-1.89]progressionpopulation-based cohortAngelidi88%0.12 [0.02-0.60]death6/6520/79Li36%0.64 [0.53-0.78]severe casepopulation-based cohortBennouar86%0.14 [0.04-0.50]death4/3015/32Vasheghani64%0.36 [0.20-0.65]ICU13/18553/323Orchard59%0.41 [0.22-0.76]ICU9/4041/75Barassi65%0.35 [0.05-2.69]death1/318/87Tehrani48%0.52 [0.29-0.96]death34/1809/25Demir89%0.11 [0.03-0.40]severe case13 (n)99 (n)Susianti91%0.09 [0.01-1.34]death0/89/42Basaran69%0.31 [0.03-0.90]severe case82/11980/85Infante55%0.45 [0.19-1.10]death4/1955/118Gavioli-5%1.05 [0.78-1.40]death80/26052/177Sulli51%0.49 [0.35-0.69]cases28/7937/51Ricci88%0.12 [0.01-2.28]death0/303/22Lohia15%0.85 [0.47-1.41]death88 (n)95 (n)Mazziotti2%0.98 [0.61-1.48]death187 (n)161 (n)Charoenngam34%0.66 [0.32-1.33]death12/10029/187Vanegas-Cedillo53%0.47 [0.28-0.81]death95/49421/57Meltzer35%0.65 [0.39-1.10]cases61/1,097118/1,251Freitas41%0.59 [0.38-0.91]death23/17968/311Bayramoğlu70%0.30 [0.09-0.77]severe case10/6024/43Livingston51%0.49 [0.25-0.83]cases16/5231/52Ünsal81%0.19 [0.01-3.87]death0/292/27Savitri88%0.12 [0.05-0.32]symp. case3/2517/17Li9%0.91 [0.79-1.06]cases610/13,650290/4,498AlSafar59%0.41 [0.16-0.99]death16/33710/127Sánchez-Zuno6%0.94 [0.44-2.02]severe case4/818/34Pimental29%0.71 [0.15-3.43]death3/172/8Diaz-Curiel73%0.27 [0.07-0.67]ICU3/21491/1,017Dror85%0.15 [0.04-0.44]severe case109/12076/133Campi24%0.76 [0.31-1.83]death6/3913/64Jude72%0.28 [0.25-0.32]hosp.n/an/aZelzer46%0.54 [0.29-0.98]death24/12110/27Jimenez-8%1.08 [0.59-1.98]death50 (n)110 (n)Cozier39%0.61 [0.39-0.96]cases94/1,60133/373Matin66%0.34 [0.21-0.56]casescase controlNimavat50%0.50 [0.19-1.27]death13/1315/25Ribeiro50%0.50 [0.28-0.87]casesn/an/aAlpcan45%0.55 [0.41-0.75]cases42/10833/47Sinaci79%0.21 [0.10-0.43]m/s case8/10023/59di Filippo11%0.89 [0.35-2.29]death5/2812/60Golabi81%0.19 [0.07-0.51]symp. casen/an/aPecina36%0.64 [0.04-6.25]death6/771/15Karonova78%0.22 [0.07-0.67]death8/9610/37Derakhshanian45%0.55 [0.30-0.98]death148 (n)142 (n)Afaghi55%0.45 [0.34-0.59]death97/53751/109Ramirez-Sandoval32%0.68 [0.57-0.83]death2,337 (n)571 (n)All studies55%0.45 [0.39-0.53]1,907/26,0331,760/14,38855% improvementAll 81 vitamin D COVID-19 sufficiency studiesvdmeta.com Oct 22, 2021Tau​2 = 0.31; I​2 = 91.6%; Z = 10.45Effect extraction pre-specified, see appendixFavors vitamin DFavors control
Figure 7. Random effects meta-analysis for sufficiency studies. This plot pools studies with different effects, different vitamin D cutoff levels and measurement times, and studies may be within hospitalized patients, excluding the risk of hospitalization. However, the prevalence of positive effects is notable.
    
  
00.250.50.7511.251.51.752+Annweiler89%0.11 [0.03-0.48]80,000IUdeath10/575/9Improvement, RR [CI]Dose (5d)TreatmentControlAnnweiler63%0.37 [0.06-2.21]80,000IUdeath3/1610/32Burahee93%0.07 [0.00-1.06]400,000IUdeath0/122/2Loucera (PSM)72%0.28 [0.20-0.39]varies (c)death193 (n)193 (n)Asimi97%0.03 [0.00-0.44]10,000IUventilation0/2709/86CT​1Sánchez-Zuno (RCT)89%0.11 [0.01-1.86]50,000IUsevere case0/224/20Tau​2 = 0.20; I​2 = 41.2%Early treatment81%0.19 [0.10-0.35]13/57030/34281% improvementTan80%0.20 [0.04-0.93]5,000IUoxygen3/1716/26Improvement, RR [CI]Dose (5d)TreatmentControlKrishnan19%0.81 [0.49-1.34]n/adeath8/1684/136Castillo (RCT)85%0.15 [0.01-2.93]0.8mg (c)death0/502/26Rastogi (RCT)53%0.47 [0.24-0.92]300,000IUviral+6/1619/24Murai (DB RCT)-49%1.49 [0.55-4.05]200,000IUdeath9/1196/118Ling80%0.20 [0.08-0.48]40,000IUdeath73 (n)253 (n)Jevalikar82%0.18 [0.02-1.69]60,000IUdeath1/1283/69Giannini37%0.63 [0.35-1.09]400,000IUdeath/ICU14/3629/55Nogués (QR)79%0.21 [0.10-0.43]0.8mg (c)death21/44762/391Lakkireddy (RCT)61%0.39 [0.08-1.91]300,000IUdeath2/445/43Lohia11%0.89 [0.32-1.89]n/adeath26 (n)69 (n)Alcala-Diaz81%0.19 [0.04-0.83]0.8mg (c)death4/7990/458Güven25%0.75 [0.37-1.24]300,000IUdeath43/11330/62Soliman (RCT)63%0.37 [0.09-2.78]200,000IUdeath7/403/16Elamir (RCT)86%0.14 [0.01-2.63]2.5μg (t)death0/253/25Yildiz81%0.19 [0.03-1.37]300,000IUdeath1/3724/170Maghbooli (DB RCT)40%0.60 [0.15-2.38]125μg (c)death3/535/53Tau​2 = 0.26; I​2 = 62.4%Late treatment56%0.44 [0.31-0.62]122/1,319381/1,99456% improvementBlanch-Rubió8%0.92 [0.63-1.36]n/acases62/1,30347/799Improvement, RR [CI]Dose (1m)TreatmentControlHernández-4%1.04 [0.26-4.10]variesdeath2/1920/197Annweiler93%0.07 [0.01-0.61]50,000IUdeath2/2910/32Cereda-73%1.73 [0.81-2.74]variesdeath7/1840/152Louca8%0.92 [0.88-0.97]n/acasespopulation-based cohortCangiano70%0.30 [0.10-0.87]50,000IUdeath3/2039/78Vasheghani30%0.70 [0.33-1.49]n/adeath7/8848/420Ma30%0.70 [0.50-0.97]n/acases49/3631,329/7,934Sulli50%0.50 [0.34-0.73]n/acases22/6643/64Mazziotti19%0.81 [0.45-1.47]variesdeath116 (n)232 (n)Meltzer36%0.64 [0.29-1.41]n/acases6/131239/3,338Ünsal71%0.29 [0.11-0.76]variespneumonia4/2814/28Oristrell43%0.57 [0.41-0.80]7.4μg (t)death2,296 (n)3,407 (n)Levitus31%0.69 [0.37-1.24]variessevere case65 (n)64 (n)Dudley22%0.78 [0.23-2.61]22,400IUsymp. case15/582/6Fasano42%0.58 [0.34-0.99]n/acases13/32992/1,157Oristrell-1%1.01 [0.93-1.09]varies (c)deathpopulation-based cohortJimenez50%0.50 [0.28-0.90]3.7μg (p)death16/9465/191Israel9%0.91 [0.85-0.97]n/ahosp.737/2,4066,216/18,453Mohseni12%0.88 [0.75-1.03]n/acases99/192242/411Sinaci90%0.10 [0.01-1.70]n/asevere case0/367/123Pecina-70%1.70 [0.36-8.20]n/adeath29 (n)63 (n)Bagheri71%0.29 [0.10-0.83]n/aprogression131 (n)379 (n)Arroyo-Díaz-12%1.12 [0.73-1.66]n/adeath50/189167/1,078Tau​2 = 0.02; I​2 = 69.0%Prophylaxis20%0.80 [0.72-0.89]1,094/8,0068,620/38,60620% improvementAll studies40%0.60 [0.53-0.68]1,229/9,8959,031/40,94240% improvementAll 47 vitamin D COVID-19 treatment studiesvdmeta.com Oct 22, 20211 CT: study uses combined treatmentTau​2 = 0.07; I​2 = 81.3%; Z = 7.95Effect extraction pre-specified, see appendixFavors vitamin DFavors control
Figure 8. Random effects meta-analysis for treatment studies. Effect extraction is pre-specified, using the most serious outcome reported, see the appendix for details.
00.250.50.7511.251.51.752+Annweiler89%0.11 [0.03-0.48]80,000IUdeath10/575/9Improvement, RR [CI]Dose (5d)TreatmentControlAnnweiler63%0.37 [0.06-2.21]80,000IUdeath3/1610/32Burahee93%0.07 [0.00-1.06]400,000IUdeath0/122/2Sánchez-Zuno (RCT)89%0.11 [0.01-1.86]50,000IUsevere case0/224/20Tau​2 = 0.06; I​2 = 10.2%Early treatment84%0.16 [0.08-0.32]13/10721/6384% improvementTan80%0.20 [0.04-0.93]5,000IUoxygen3/1716/26Improvement, RR [CI]Dose (5d)TreatmentControlKrishnan19%0.81 [0.49-1.34]n/adeath8/1684/136Castillo (RCT)85%0.15 [0.01-2.93]0.8mg (c)death0/502/26Rastogi (RCT)53%0.47 [0.24-0.92]300,000IUviral+6/1619/24Murai (DB RCT)-49%1.49 [0.55-4.05]200,000IUdeath9/1196/118Ling80%0.20 [0.08-0.48]40,000IUdeath73 (n)253 (n)Jevalikar82%0.18 [0.02-1.69]60,000IUdeath1/1283/69Giannini37%0.63 [0.35-1.09]