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Vitamin D for COVID-19: real-time meta analysis of 94 treatment and 137 sufficiency studies
https://vdmeta.com/
 
0 0.5 1 1.5+ All studies 36% 94 180,794 Improvement, Studies, Patients Relative Risk Mortality 35% 55 61,289 Ventilation 31% 16 7,746 ICU admission 49% 24 40,043 Hospitalization 18% 19 85,094 Cases 12% 22 133,877 RCTs 39% 22 41,468 Peer-reviewed 36% 86 175,960 Sufficiency 55% 137 130,420 Cholecalciferol 34% 84 172,317 Calcifediol 52% 10 8,477 Prophylaxis 30% 48 129,222 Early 67% 8 43,422 Late 45% 38 8,150 Vitamin D for COVID-19 vdmeta.com Oct 2022 Favorsvitamin D Favorscontrol after exclusions
Statistically significant improvements are seen in treatment studies for mortality, ICU admission, hospitalization, and cases. 45 studies from 42 independent teams in 17 different countries show statistically significant improvements in isolation (32 for the most serious outcome).
Random effects meta-analysis with pooled effects using the most serious outcome reported shows 67% [43‑81%] and 36% [29‑42%] improvement for early treatment and for all studies. Results are similar after restriction to 86 peer-reviewed studies: 63% [39‑78%] and 36% [29‑42%], and for the 55 mortality results: 68% [39‑84%] and 35% [25‑43%].
Acute treatment (early 67% [43‑81%], late 45% [31‑56%]) shows greater efficacy than chronic prophylaxis (30% [20‑38%]), suggesting that long-term supplementation may not be ideal.
Late stage treatment with calcifediol/calcitriol shows greater improvement compared to cholecalciferol: 73% [57‑83%] vs. 38% [23‑50%].
0 0.5 1 1.5+ All studies 36% 94 180,794 Improvement, Studies, Patients Relative Risk Mortality 35% 55 61,289 Ventilation 31% 16 7,746 ICU admission 49% 24 40,043 Hospitalization 18% 19 85,094 Cases 12% 22 133,877 RCTs 39% 22 41,468 Peer-reviewed 36% 86 175,960 Sufficiency 55% 137 130,420 Cholecalciferol 34% 84 172,317 Calcifediol 52% 10 8,477 Prophylaxis 30% 48 129,222 Early 67% 8 43,422 Late 45% 38 8,150 Vitamin D for COVID-19 vdmeta.com Oct 2022 Favorsvitamin D Favorscontrol after exclusions
Sufficiency studies show a strong association between vitamin D sufficiency and outcomes. Meta analysis of the 137 studies using the most serious outcome reported shows 55% [50‑59%] improvement.
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 may be more effective. Only 14% of vitamin D studies show zero events with treatment. The quality of non-prescription supplements can vary widely [Crawford, Crighton].
All data to reproduce this paper and the sources are in the appendix.
ImprovementStudies AuthorsPatients
Treatment RCTs 39% [17‑55%] 22 272 41,468
Treatment studies 36% [29‑42%] 94 960 180,794
Cholecalciferol treatment 34% [27‑41%] 84 838 172,317
Calcifediol/calcitriol treatment 52% [26‑69%] 10 122 8,477
Treatment mortality 35% [25‑43%] 55 521 61,289
Sufficiency studies 55% [50‑59%] 137 1,210 130,420
Highlights
Vitamin D reduces risk for COVID-19 with very high confidence for mortality, ICU admission, hospitalization, recovery, and in pooled analysis, high confidence for cases, and low confidence for ventilation, progression, and viral clearance.
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 47 treatments.
    
  
A
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Annweiler 89% 0.11 [0.03-0.48] 80,000IU death 10/57 5/9 Improvement, RR [CI] Dose (5d) Treatment Control Annweiler 63% 0.37 [0.06-2.21] 80,000IU death 3/16 10/32 Burahee 93% 0.07 [0.00-1.06] 400,000IU death 0/12 2/2 Asimi 97% 0.03 [0.00-0.44] 10,000IU ventilation 0/270 9/86 CT​1 Sánchez-Zuno (RCT) 89% 0.11 [0.01-0.91] 50,000IU severe case 0/22 4/20 Efird 49% 0.51 [0.23-1.17] varies death 11/544 413/15,794 Khan (RCT) 33% 0.67 [0.37-1.19] 1,800IU no recov. 10/25 15/25 CT​1 Hunt 47% 0.53 [0.37-0.77] n/a death 43/1,019 1,569/25,489 Tau​2 = 0.30, I​2 = 67.4%, p < 0.0001 Early treatment 67% 0.33 [0.19-0.57] 77/1,965 2,027/41,457 67% improvement Tan 80% 0.20 [0.04-0.93] 5,000IU oxygen 3/17 16/26 CT​1 Improvement, RR [CI] Dose (5d) Treatment Control Krishnan 19% 0.81 [0.49-1.34] n/a death 8/16 84/136 Castillo (RCT) 85% 0.15 [0.01-2.93] 0.8mg (c) death 0/50 2/26 Rastogi (RCT) 53% 0.47 [0.24-0.92] 300,000IU viral+ 6/16 19/24 Murai (DB RCT) -49% 1.49 [0.55-4.05] 200,000IU death 9/119 6/118 Ling 80% 0.20 [0.08-0.48] 40,000IU death 73 (n) 253 (n) Jevalikar 82% 0.18 [0.02-1.69] 60,000IU death 1/128 3/69 Giannini 37% 0.63 [0.35-1.09] 400,000IU death/ICU 14/36 29/55 Nogués (QR) 79% 0.21 [0.10-0.43] 0.8mg (c) death 21/447 62/391 Lohia 11% 0.89 [0.32-1.89] n/a death 26 (n) 69 (n) Mazziotti 19% 0.81 [0.45-1.47] varies death 116 (n) 232 (n) Elhadi (ICU) 23% 0.77 [0.44-1.32] n/a death 7/15 274/450 ICU patients Alcala-Diaz 81% 0.19 [0.04-0.83] 0.8mg (c) death 4/79 90/458 Güven (ICU) 25% 0.75 [0.37-1.24] 300,000IU death 43/113 30/62 ICU patients Assiri (ICU) -66% 1.66 [0.25-7.87] n/a death 12/90 2/28 ICU patients Soliman (RCT) 63% 0.37 [0.09-2.78] 200,000IU death 7/40 3/16 Elamir (RCT) 86% 0.14 [0.01-2.63] 2.5μg (t) death 0/25 3/25 Yildiz 81% 0.19 [0.04-0.91] 300,000IU death 1/37 24/170 Maghbooli (DB RCT) 40% 0.60 [0.15-2.38] 125μg (c) death 3/53 5/53 Leal-Martínez (RCT) 86% 0.14 [0.03-0.80] 20,000IU death 1/40 7/40 CT​1 Beigm.. (SB RCT) 89% 0.11 [0.01-1.98] 600,000IU death 0/30 4/30 ICU patients CT​1 Baguma 97% 0.03 [0.00-0.54] n/a death 23 (n) 458 (n) Mahmood 30% 0.70 [0.47-1.04] varies death 45/238 31/114 Bishop (DB RCT) 34% 0.66 [0.23-1.92] 1020μg (c) no recov. 5/65 8/69 Cannata-An.. (RCT) -44% 1.44 [0.76-2.72] 100,000IU death 22/274 15/269 Zangeneh (ICU) -26% 1.26 [0.73-2.16] n/a death n/a n/a ICU patients Fiore 93% 0.07 [0.07-0.63] 200,000IU death 3/58 11/58 Mariani (DB RCT) -124% 2.24 [0.44-11.3] 500,000IU death 5/115 2/103 Baykal 22% 0.78 [0.41-1.47] 300,000IU death 7/18 28/56 Singh (DB RCT) 45% 0.55 [0.31-0.99] 600,000IU death 11/45 20/45 Shahid 38% 0.62 [0.47-0.82] n/a death 705 (n) 773 (n) Karonova (RCT) 86% 0.14 [0.01-2.66] 50,000IU ICU 0/56 3/54 Zurita-C.. (SB RCT) 79% 0.21 [0.03-1.59] 10,000IU death 1/20 6/25 De Niet (DB RCT) 65% 0.35 [0.04-3.10] 100,000IU death 1/21 3/22 Fairfield -9% 1.09 [1.04-1.12] n/a death Lakkireddy (RCT) 61% 0.39 [0.08-1.91] 300,000IU death 2/44 5/43 see notes Hafez 94% 0.06 [0.00-1.29] 150,000IU death 0/7 12/30 Sharif-Askari (ICU) 36% 0.64 [0.46-0.90] 50,000IU ICU 20 (n) 25 (n) ICU patients Tau​2 = 0.26, I​2 = 80.1%, p < 0.0001 Late treatment 45% 0.55 [0.44-0.69] 242/3,275 807/4,875 45% improvement Blanch-Rubió 8% 0.92 [0.63-1.36] n/a cases 62/1,303 47/799 Improvement, RR [CI] Dose (1m) Treatment Control Sainz-Amo 33% 0.67 [0.27-1.67] n/a severe case case control Hernández -4% 1.04 [0.26-4.10] varies death 2/19 20/197 Annweiler 93% 0.07 [0.01-0.61] 50,000IU death 2/29 10/32 Cereda -73% 1.73 [0.81-2.74] varies death 7/18 40/152 Louca 8% 0.92 [0.88-0.97] n/a cases population-based cohort Cangiano 70% 0.30 [0.10-0.87] 50,000IU death 3/20 39/78 Vasheghani 30% 0.70 [0.33-1.49] n/a death 7/88 48/420 Ma 30% 0.70 [0.50-0.97] n/a cases 49/363 1,329/7,934 Sulli 76% 0.24 [0.17-0.36] n/a cases case control Ullah -42% 1.42 [0.74-2.37] n/a death 21/64 26/135 Meltzer 36% 0.64 [0.29-1.41] n/a cases 6/131 239/3,338 Holt 7% 0.93 [0.76-1.15] n/a cases 141/5,640 305/9,587 Ünsal 71% 0.29 [0.11-0.76] varies pneumonia 4/28 14/28 Oristrell 43% 0.57 [0.41-0.80] 7.4μg (t) death 2,296 (n) 3,407 (n) Abdulateef 41% 0.59 [0.25-1.41] varies hosp. 6/127 24/300 Loucera (PSM) 33% 0.67 [0.50-0.91] varies (c) death 374 (n) 374 (n) Levitus 31% 0.69 [0.37-1.24] varies severe case 65 (n) 64 (n) Aldwihi -49% 1.49 [1.13-1.87] n/a hosp. 94/259 143/479 Dudley 22% 0.78 [0.23-2.61] 22,400IU symp. case 15/58 2/6 Fasano 42% 0.58 [0.34-0.99] n/a cases 13/329 92/1,157 Campi 88% 0.12 [0.09-0.15] n/a severe case case control Oristrell -1% 1.01 [0.93-1.09] varies (c) death population-based cohort Jimenez 50% 0.50 [0.28-0.90] 3.7μg (p) death 16/94 65/191 Israel 13% 0.87 [0.79-0.95] n/a hosp. case control Mohseni 12% 0.88 [0.75-1.03] n/a cases 99/192 242/411 Sinaci 90% 0.10 [0.01-1.70] n/a severe case 0/36 7/123 Golabi -25% 1.25 [0.86-1.84] n/a cases case control Pecina -70% 1.70 [0.36-8.20] n/a death 29 (n) 63 (n) Bagheri 71% 0.29 [0.10-0.83] n/a progression 131 (n) 379 (n) Lázaro 27% 0.73 [0.07-7.96] n/a cases 1/97 2/142 Arroyo-Díaz -12% 1.12 [0.73-1.66] n/a death 50/189 167/1,078 Ahmed 10% 0.90 [0.72-1.07] n/a death n/a n/a Ma 49% 0.51 [0.29-0.91] varies hosp. 26,605 (n) 12,710 (n) Mahmood 9% 0.91 [0.60-1.38] varies death 34/138 31/114 Tylicki 14% 0.86 [0.40-1.38] n/a death 28/85 25/48 Subramanian 27% 0.73 [0.47-1.09] n/a death 31/131 80/336 Levy 30% 0.70 [0.49-1.00] n/a death/hosp. 39/208 168/641 Junior 22% 0.78 [0.30-1.99] n/a death 8/113 8/88 Nimer 33% 0.67 [0.48-0.90] n/a hosp. 66/796 153/1,352 Shehab 46% 0.54 [0.23-1.30] n/a severe case 6/90 20/163 Jolliffe (RCT) -95% 1.95 [0.12-31.1] 89,600IU ventilation 1/1,515 1/2,949 Parant 50% 0.50 [0.20-1.17] varies death 7/66 28/162 Villasis.. (DB RCT) 67% 0.33 [0.01-8.15] 112,000IU hosp. 0/150 1/152 Jabeen 89% 0.11 [0.01-1.94] 200,000IU symp. case 0/20 4/20 Hosseini (DB RCT) 82% 0.18 [0.01-3.50] 140,000IU cases 0/19 2/15 Brunvoll (DB RCT) -0% 1.00 [0.25-4.01] 11,200IU ICU 4/17,278 4/17,323 CT​1 van Helmond 98% 0.02 [0.00-1.35] 140,000IU cases 0/255 36/2,827 Tau​2 = 0.10, I​2 = 87.5%, p < 0.0001 Prophylaxis 30% 0.70 [0.62-0.80] 822/59,448 3,422/69,774 30% improvement All studies 36% 0.64 [0.58-0.71] 1,141/64,688 6,256/116,106 36% improvement All 94 vitamin D COVID-19 treatment studies vdmeta.com Oct 2022 Tau​2 = 0.09, I​2 = 86.3%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 CT: study uses combined treatment Favors vitamin D Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Annweiler 89% death Improvement Relative Risk [CI] Annweiler 63% death Burahee 93% death Asimi 97% ventilation CT​1 Sánchez-Zuno (RCT) 89% severe case Efird 49% death Khan (RCT) 33% recovery CT​1 Hunt 47% death Tau​2 = 0.30, I​2 = 67.4%, p < 0.0001 Early treatment 67% 67% improvement Tan 80% oxygen therapy CT​1 Krishnan 19% death Castillo (RCT) 85% death Rastogi (RCT) 53% viral- Murai (DB RCT) -49% death Ling 80% death Jevalikar 82% death Giannini 37% death/ICU Nogués (QR) 79% death Lohia 11% death Mazziotti 19% death Elhadi (ICU) 23% death ICU patients Alcala-Diaz 81% death Güven (ICU) 25% death ICU patients Assiri (ICU) -66% death ICU patients Soliman (RCT) 63% death Elamir (RCT) 86% death Yildiz 81% death Maghbooli (DB RCT) 40% death Leal-Martínez (RCT) 86% death CT​1 Beigm.. (SB RCT) 89% death ICU patients CT​1 Baguma 97% death Mahmood 30% death Bishop (DB RCT) 34% recovery Cannata-An.. (RCT) -44% death Zangeneh (ICU) -26% death ICU patients Fiore 93% death Mariani (DB RCT) -124% death Baykal 22% death Singh (DB RCT) 45% death Shahid 38% death Karonova (RCT) 86% ICU admission Zurita-C.. (SB RCT) 79% death De Niet (DB RCT) 65% death Fairfield -9% death Lakkireddy (RCT) 61% death see notes Hafez 94% death Sharif-Askari (ICU) 36% ICU admission ICU patients Tau​2 = 0.26, I​2 = 80.1%, p < 0.0001 Late treatment 45% 45% improvement Blanch-Rubió 8% case Sainz-Amo 33% severe case Hernández -4% death Annweiler 93% death Cereda -73% death Louca 8% case Cangiano 70% death Vasheghani 30% death Ma 30% case Sulli 76% case Ullah -42% death Meltzer 36% case Holt 7% case Ünsal 71% pneumonia Oristrell 43% death Abdulateef 41% hospitalization Loucera (PSM) 33% death Levitus 31% severe case Aldwihi -49% hospitalization Dudley 22% symp. case Fasano 42% case Campi 88% severe case Oristrell -1% death Jimenez 50% death Israel 13% hospitalization Mohseni 12% case Sinaci 90% severe case Golabi -25% case Pecina -70% death Bagheri 71% progression Lázaro 27% case Arroyo-Díaz -12% death Ahmed 10% death Ma 49% hospitalization Mahmood 9% death Tylicki 14% death Subramanian 27% death Levy 30% death/hosp. Junior 22% death Nimer 33% hospitalization Shehab 46% severe case Jolliffe (RCT) -95% ventilation Parant 50% death Villasis.. (DB RCT) 67% hospitalization Jabeen 89% symp. case Hosseini (DB RCT) 82% case Brunvoll (DB RCT) -0% ICU admission CT​1 van Helmond 98% case Tau​2 = 0.10, I​2 = 87.5%, p < 0.0001 Prophylaxis 30% 30% improvement All studies 36% 36% improvement All 94 vitamin D COVID-19 treatment studies vdmeta.com Oct 2022 Tau​2 = 0.09, I​2 = 86.3%, p < 0.0001 Protocol pre-specified/rotate for details1 CT: study uses combined treatment Favors vitamin D Favors 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, Gupta, 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, Alarslan, Azadeh, Chodick, D'Avolio, Desai, Ersöz, Jabbar, Kerget, Latifi-Pupovci, Mansour, Mardani, Nicolescu, Ranjbar, Saeed, Schmitt, Shannak, Sinnberg, Soltani-Zangbar, Takase, Vassiliou], most of which show lower D levels for worse outcomes. Other studies analyze vitamin D status and outcomes in geographic regions [Bakaloudi, Jayawardena, Marik, Papadimitriou, Rhodes, Sooriyaarachchi, Walrand, Yadav], all finding worse outcomes to be more likely with lower D levels.
Sufficiency studies vary widely in terms of when vitamin D levels were measured, the cutoff level used, and the population analyzed (for example studies with hospitalized patients exclude the effect of vitamin D on the risk of hospitalization). We do not analyze sufficiency studies in more detail because there are many controlled treatment studies that provide better information on the use of vitamin D as a treatment for COVID-19. A more detailed analysis of sufficiency studies can be found in [Chiodini]. [Mishra] present a systematic review and meta analysis showing that vitamin D levels are significantly associated with COVID-19 cases.
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.
Preclinical Research
5 In Silico studies support the efficacy of vitamin D [Al-Mazaideh, Chellasamy, Pandya, Qayyum, Song].
2 In Vitro studies support the efficacy of vitamin D [Mok, Pickard].
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 5 shows a visual overview of the results. Figure 1 shows a forest plot for all treatment studies, and the effects reported in sufficiency studies and treatment studies. Figure 6 and 7 show results by treatment stage. Figure 8 shows a forest plot for random effects meta-analysis of sufficiency studies, while Figure 9, 10, 11, 12, 13, 14, 15, 16, and 17 show forest plots for all treatment studies with pooled effects, cholecalciferol studies, calcifediol/calcitriol studies, and for studies reporting mortality, mechanical ventilation, ICU admission, hospitalization, and case results only. Table 1 summarizes the results.
0 0.5 1 1.5+ ALL STUDIES MORTALITY VENTILATION ICU ADMISSION HOSPITALIZATION CASES RANDOMIZED CONTROLLED TRIALS PEER-REVIEWED SUFFICIENCY CHOLECALCIFEROL CALCIFEDIOL After Exclusions ALL STUDIES RANDOMIZED CONTROLLED TRIALS All Prophylaxis Early Late Vitamin D for COVID-19 VDMETA.COM OCT 2022
Figure 5. Overview of 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 128 137 93.4% 55% improvement
RR 0.45 [0.41‑0.50]
p < 0.0001
Early treatment 8 8 100% 67% improvement
RR 0.33 [0.19‑0.57]
p < 0.0001
Late treatment 32 38 84.2% 45% improvement
RR 0.55 [0.44‑0.69]
p < 0.0001
Prophylaxis 38 48 79.2% 30% improvement
RR 0.70 [0.62‑0.80]
p < 0.0001
All treatment studies 78 94 83.0% 36% improvement
RR 0.64 [0.58‑0.71]
p < 0.0001
Table 1. Results.
    
  
Figure 6. Results by treatment stage.
    
  
Figure 7. Results by treatment stage.
    
  
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Lau 45% 0.55 [0.18-1.68] ICU 2/5 11/15 Improvement, RR [CI] High Levels Low Levels Reyes Pérez 62% 0.38 [0.18-0.73] death 21/137 14/35 Mendy 7% 0.93 [0.33-2.47] death 21/600 5/89 Panagiotou 52% 0.48 [0.24-0.95] ICU 8/44 34/90 Faul 69% 0.31 [0.10-0.95] ventilation 4/21 8/12 Merzon 46% 0.54 [0.23-1.02] hosp. 79 (n) 703 (n) Anjum 62% 0.38 [0.17-0.82] death 8/80 16/60 Carpagnano 71% 0.29 [0.10-0.85] death 5/34 4/8 Im 73% 0.27 [0.15-0.47] cases case control Hastie 17% 0.83 [0.57-1.20] death population-based cohort Baktash 29% 0.71 [0.18-2.78] death 4/31 6/39 Meltzer 44% 0.56 [0.36-0.89] cases 39/317 32/172 Israel 34% 0.66 [0.54-0.81] severe case case control Radujkovic 93% 0.07 [0.01-0.34] death 144 (n) 12 (n) Kaufman 53% 0.47 [0.30-0.74] cases 12,321 (n) 39,190 (n) Maghbooli 52% 0.48 [0.22-1.05] death 7/72 27/134 Pepkowitz 56% 0.44 [0.25-0.78] ICU 9/24 11/13 Karahan 83% 0.17 [0.08-0.41] death 5/46 64/103 Yılmaz 73% 0.27 [0.01-5.14] severe case 0/11 2/29 Faniyi 29% 0.71 [0.59-0.86] seropositive 170/331 44/61 Ye 93% 0.07 [0.01-0.81] hosp. 2/36 8/26 Macaya 55% 0.45 [0.15-1.06] severe case 11/35 20/45 Tomasa-Irriguible 35% 0.65 [0.31-1.24] ventilation 15/27 18/78 Hernández 83% 0.17 [0.07-0.41] death/ICU 35 (n) 162 (n) Abrishami 76% 0.24 [0.06-0.93] death 3/47 9/26 Cereda -120% 2.20 [1.01-3.22]