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1Department of Biostatistics and Medical Informatics, Firat University School of Medicine, Elazığ, Turkey
2Department of Statistics, Faculty of Science, Fırat University, Elazığ, Turkey
3Department of Family Medicine, Firat University School of Medicine, Elazığ, Turkey
©2021, Korean Society of Epidemiology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICT OF INTEREST
The authors have no conflicts of interest to declare for this study.
Funding
None.
AUTHOR CONTRIBUTIONS
Conceptualization: MOK, EP, BY. Data curation: MOK, EP. Formal analysis: MOK, EP. Funding acquisition: None. Methodology: MOK, EP, BY. Visualization: MOK, EP. Writing – original draft: MOK, EP. Writing – review & editing: MOK, EP, BY.
Study | Location | Region | Study design | Sample size | Gender (men), n (%) | Population age mean±SD or median [Min-Max or IQR] | The definition of VDD and/or VDIS | Outcomes evaluated in the study | Included in the meta-analysis |
---|---|---|---|---|---|---|---|---|---|
Abdollahi et al. [27] | Iran | Asia | Case-control | 402 | 132 (32.8) | 47.1±15.3 | VDD<10 ng/mL | I | Yes |
VDIS<30 ng/mL | |||||||||
Baktash et al. [28] | UK | Europe | Cross-sectional | 105 | 57 (54.2) | 81 [65-102] | VDD<30 nmol/L | I-M | Yes |
Campi et al. [29] | Italy | Europe | Cohort | 361 | 243 (67.0) | 66 [54–78] | VDD<50 nmol/L | I-S-M | Yes |
Cereda et al. [30] | Italy | Europe | Cohort | 129 | 70 (54.3) | 77 [65–85] | VDD<20 ng/mL | S-M | Yes |
VDIS<30 ng/mL | |||||||||
D’Avolio et al. [21] | Switzerland | Europe | Case-control | 1,484 | 682 (45.9) | NR | NR | I | No |
Darling et al. [22] | UK | Europe | Case-control | 1,303 | 713 (54.7) | 57.7±8.7 | NR | I | No |
De Smet et al. [31] | Belgium | Europe | Cross-sectional | 2,903 | 1,108 (38.1) | NR | VDD<20 ng/mL | I-S | Yes |
Hastie et al. [23] | UK | Europe | Cohort | 341,484 | NR | NR | VDD<25 nmol/L | I-M | No |
VDIS<50 nmol/L | |||||||||
Hernández et al. [32] | Spain | Europe | Case-control | 413 | 253 (61.2) | NR | VDD<20 ng/mL | I-S-M | Yes |
Im et al. [24] | Korea | Asia | Case-control | 200 | 84 (42.0) | 52.3±20.3 | VDD<20 ng/dL | I-S | No |
Israel et al. [33] | Israel | Asia | Case-control | 576,455 | 271,601 (47.1) | NR | VDD<50 nmol/L | I | Yes |
Karahan and KatKat [34] | Turkey | Europe | Cross-sectional | 149 | 81 (54.3) | 63.5±15.3 | VDD<20 ng/mL | S-M | Yes |
VDIS<30 ng/mL | |||||||||
Katz et al. [25] | USA | America | Case-control | 987,849 | 455,458 (46.1) | NR | NR | I | No |
Li et al. [35] | UK | Europe | Case-control | 353,299 | 161,298 (45.6) | 67.7±8.1 | VDD<25 nmol/L | I-H-S | Yes |
VDIS<50 nmol/L | |||||||||
Livingston et al. [36] | UK | Europe | Cohort | 104 | 39 (37.5) | 68.5±18.3 | VDSL<34.4 nmol/L | I | Yes |
Luo et al. [37] | China | Asia | Cross-sectional | 895 | 405 (45.2) | NR | VDD<30 nmol/L | I-S-M | Yes |
Macaya et al. [38] | Spain | Europe | Cohort | 80 | 35 (43.7) | NR | VDD<20 ng/mL | S | Yes |
Maghbooli et al. [39] | Iran | Asia | Cross-sectional | 235 | 144 (61.3) | 58.7±15.2 | VDD<20 ng/mL | H-S-M | Yes |
VDIS<30 ng/mL | |||||||||
Mardani et al. [40] | Iran | Asia | Cross-sectional | 123 | 65 (52.8) | 42.1±14,9 | VDD<10 ng/mL | I | Yes |
VDIS<30 ng/mL | |||||||||
Meltzer et al. [41] | USA | America | Case-control | 489 | 123 (25.0) | 49.2±18.4 | VDD<20 ng/mL | I | Yes |
Mendy et al. [42] | USA | America | Cohort | 689 | 365 (53.0) | 49.5 [35.2–67.5] | NR | H-S | Yes |
Merzon et al. [43] | Israel | Asia | Case-control | 7,807 | 3,234 (41.4) | 41.4±NR | VDD<20 ng/mL | I-H | Yes |
VDIS<30 ng/mL | |||||||||
Panagiotou et al. [44] | UK | Europe | Cohort | 134 | 73 (54.4) | 68.7±14.0 | VDD<25 nmol/L | S | Yes |
VDIS<50 nmol/L | |||||||||
Radujkovic et al. [45] | Germany | Europe | Cohort | 185 | 95 (51.0) | 60 [49–70] | VDD<12 ng/mL | S-M | Yes |
VDIS<20 ng/mL | |||||||||
Vasiliou et al. [46] | Greece | Europe | Cohort | 39 | 31 (79.4) | 61.5±13.2 | VDD<20 ng/mL | H-M | Yes |
VDIS<30 ng/mL | |||||||||
Ye et al. [47] | China | Asia | Case-control | 142 | 55 (38.7) | NR [0.1-85] | VDD<50 nmol/L | I-S | Yes |
VDIS<75 nmol/L |
Study | Sample size in the study |
Sample size included in meta-analyses |
Outcomes evaluated in the study | Outcomes evaluated in the meta-analyses | Findings in the study1 | Limitations in extracting data | ||
---|---|---|---|---|---|---|---|---|
D-CIMA | D-CSMA | D-CMMA | ||||||
Abdollahi et al. [27] | 402 | 402 | – | – | I | I | I(+) | VDD was defined as <10 ng/mL, but the sample distribution for VDD was not suitable for statistical analysis; A statistical comparison was made for VDIS <30 ng/mL; Therefore, the data belonging to VDIS were included in the meta-analysis, and the measurement unit was assigned as “other” |
Baktash et al. [28] | 105 | – | – | 70 | I-M | M | I(+); M(-) | There was uncertainty in the definition of comparison groups for COVID-19 infection; We sent an email to the corresponding author, but we did not receive a reply; Therefore, COVID-19 infection data were not included in the D-CIMA |
Campi et al. [29] | 361 | 361 | 103 | 103 | I-S-M | I-S-M | I(+); S(+); M(+) | There was no limitation in data extraction |
Cereda et al. [30] | 129 | – | 129 | 129 | S-M | S-M | S(+); M(+) | The clinical outcomes were severe pneumonia, admission to the ICU, and in-hospital mortality; The ICU admission data were not appropriate for statistical analysis (0 observed cases); Therefore, we extracted data from severe pneumonia for the analysis of severity |
D’Avolio et al. [21] | 1,484 | – | – | – | I | – | I(+) | The definition of VDD was not available; There was no adequate information dealing with descriptive statistics; VDD was presented as median (IQR) and the findings were presented graphically; Since we extracted the data based on the number of cases, we did not include it in the meta-analysis In the study, the date of the data received from UK Biobank for the COVID-19 (-) control group was long ago; There was no VDD definition and they used quartile values of VDD; Since we extracted the data based on the number of cases, we did not include it in the meta-analysis |
Darling et al. [22] | 1,303 | – | – | – | I | – | I(-) | In the study, the date of the data received from UK Biobank for the COVID-19 (-) control group was long ago; There was no VDD definition and they used quartile values of VDD; Since we extracted the data based on the number of cases, we did not include it in the meta-analysis |
De Smet et al. [31] | 2,903 | 2,903 | 186 | – | I-S | I-S | I(+); S(+) | In the study, chest CT was performed for all COVID-19 patients to determine the disease stage; They classified the patients as stage 1 (early stage), stage 2 (progressive stage), and stage 3 (peak stage); We chose severe cases from stage 3 and non-severe cases from stage 1-2 |
Hastie et al. [23] | 341,484 | – | – | – | I-M | – | I(-); M(-) | There was no adequate information dealing with descriptive statistics; The findings were presented by using HR and IRR values; Since we extracted the data based on the number of cases, we did not include it in the meta-analysis |
Hernández et al. [32] | 413 | – | 197 | 197 | I-S-M | S-M | I(+); S(-); M(-) | For COVID-19 infection, VDD was presented as mean (±SD); Since the number of cases was not reported, we could not include it in D-CIMA |
Im et al. [24] | 200 | – | – | – | I-S | – | I(+); S(+) | In the study, the unit of ng/dL was used for laboratory measurements of serum 25(OH)D levels, and VDD was defined as 25(OH)D<20 ng/dL; We converted 20 ng/dL to 0.2 ng/mL; Since we thought there was an inconsistency, we could not include these data in the meta analyses |
Israel et al. [33] | 576,455 | 187,234 | – | – | I | I | I(+) | Age matching was performed between the case and control groups, but single summary statistics for the population were not presented |
Karahan and Katkat [34] | 149 | – | 149 | 149 | S-M | S-M | S(+); M(+) | There was no limitation in data extraction |
Katz et al. [25] | 987,849 | – | – | – | I | – | I(+) | There was no adequate information dealing with descriptive statistics; The findings were presented as ORs; Since we extracted the data based on the number of cases, we did not include it in the meta-analysis |
Li et al. [35] | 353,299 | 3,502 | 1,082 | – | I-H-S | I-S | I(+); H(+); S(+) | This study defined hospitalization as one record of origin (whether the patient s tested positive or not); In the study, hospitalized, confirmed, and severe COVID-19 cases were compared with community controls; We think that this study design is inappropriate; For this reason, we extracted data on infections from patients who presented to the hospital with suspected COVID-19 and confirmed COVID-19, and for the severity from patients with confirmed and severe COVID-19 |
Livingston et al. [36] | 104 | 104 | – | – | I | I | I(-) | The definition of VDD was not available; Statistical comparisons were performed for 25(OH)D <34.4 nmol/L; Therefore, the data belonging to this distinction were included in the meta-analysis, and the measurement unit was assigned as “other” |
Luo et al. [37] | 895 | 895 | 335 | 74 | I-S-M | I-S-M | I(+); S(+); M(-) | There was no limitation in data extraction |
Macaya et al. [38] | 80 | – | 80 | S | S | S(+) | There was no limitation in data extraction | |
Maghbooli et al. [39] | 235 | – | 235 | 235 | H-S-M | S-M | H(+); S(+); M(+) | There was no limitation in data extraction; Although the authors defined VDD as 25(OH)D<20 ng/mL, the dataset that could be extracted from the article belonged to the category of 25(OH)D<30 ng/mL; Therefore, it was included in the overall analysis |
Mardani et al. [40] | 123 | 123 | – | – | I | I | I(+) | We extracted data from their supplementary file according to 25(OH)D<20 ng/mL |
Meltzer et al. [41] | 489 | 489 | – | – | I | I | I(+) | There was no limitation in data extraction |
Mendy et al. [42] | 689 | – | 689 | – | H-S | S | H(+); S(+) | The definition of VDD was not available; Therefore, the measurement unit was assigned as “other” in the D-CSMA |
Merzon et al. [43] | 7,807 | 7,807 | – | – | I-H | I | I(+); H(+) | There was no limitation in data extraction |
Panagiotou et al. [44] | 134 | – | 134 | – | S | S | S(+) | The authors classified the patients as admitted to the ITU and non-ITU wards; |
When we extracted data, we chose patients admitted to non-ITU wards as non-severe and those admitted to ITU wards as severe; A statistical comparison was made for VDIS <50 nmol/L; Therefore, the data belong to VDIS were included in the D-CSMA | ||||||||
Radujkovic et al. [45] | 185 | – | 185 | – | S-M | S | S(+); M(+) | The authors classified patients as inpatients and outpatients; When we extracted data, we chose the outpatients as non-severe and the inpatients as severe according to their definition |
Vassiliou et al. [46] | 39 | – | – | 39 | H-M | M | H(-); M(-) | There was no limitation in data extraction |
Ye et al. [47] | 142 | 142 | 60 | – | I-S | I-S | I(+); S(+) | There was no limitation in data extraction |
Total | 2,277,860 | 203,962 | 3,564 | 996 |
COVID-19, coronavirus disease 2019; D-CIMA, vitamin D and COVID-19 infection meta-analysis; D-CSMA, vitamin D and COVID-19 severity meta-analysis; D-CMMA, vitamin D and COVID-19 mortality meta-analysis; I, COVID-19 infection; S, severity; M, mortality; H, hospitalization; VDD, vitamin D deficiency; ICU, intensive care unit; IQR, interquartile range; CT, computed tomography; HR, hazard ratio; IRR, incidence rate ratio; SD, standard deviation; OR, odds ratio; ITU, intensive therapy unit; VDIS, vitamin D insufficiency.
1 (+), indicates that the association of low levels of vitamin D and I, S, M and H was statistically significant; (-) indicates that the association of low levels of vitamin D and I, S, M and H was not statistically significant.
Meta-analyses |
Publication bias |
Heterogeneity |
Quantifying heterogeneity |
Findings of meta-analyses |
|
---|---|---|---|---|---|
Egger test (p-value) | Cochran Q test (p-value) | I2 (95% CI), %/τ2 (95% CI) |
Peto random-effect model |
||
OR (95% CI) | p-value | ||||
D-CIMA for serum 25(OH)D levels <20 ng/mL and 50 nmol/L | 0.399 | <0.001 | 85.4 (73.2, 92.1)/0.06 (0.05, 1.02) | 1.64 (1.32, 2.04) | <0.001 |
D-CIMAOverall for serum 25(OH)D levels with all different measurement units | 0.091 | <0.001 | 87.0 (78.7, 92.1)/0.08 (0.06, 0.76) | 1.86 (1.51, 2.30) | <0.001 |
D-CSMA for serum 25(OH)D levels <20 ng/mL and 50 nmol/L | 0.064 | <0.001 | 91.5 (86.1, 94.8)/1.18 (0.47. 5.29) | 2.42 (1.13, 5.17) | 0.022 |
D-CSMAOverall for serum 25(OH)D levels with all different measurement units | 0.017 | <0.001 | 92.8 (90.2, 94.7)1/1.37 (0.88, 3.98)1 | 1.24 (0.71, 2.17)1 | 0.445 |
D-CMMA for serum 25(OH)D levels <20 ng/mL and 50 nmol/L | 0.911 | <0.001 | 82.6 (60.1, 92.4)/1.30 (0.12, 10.51) | 1.64 (0.53, 5.06) | 0.390 |
D-CMMAOverall for serum 25(OH)D levels with all different measurement units | 0.909 | 0.001 | 70.8 (39.7, 85.9)/0.71 (0.00, 3.02) | 1.58 (0.76, 3.27) | 0.211 |
Study | Location | Region | Study design | Sample size | Gender (men), n (%) | Population age mean±SD or median [Min-Max or IQR] | The definition of VDD and/or VDIS | Outcomes evaluated in the study | Included in the meta-analysis |
---|---|---|---|---|---|---|---|---|---|
Abdollahi et al. [27] | Iran | Asia | Case-control | 402 | 132 (32.8) | 47.1±15.3 | VDD<10 ng/mL | I | Yes |
VDIS<30 ng/mL | |||||||||
Baktash et al. [28] | UK | Europe | Cross-sectional | 105 | 57 (54.2) | 81 [65-102] | VDD<30 nmol/L | I-M | Yes |
Campi et al. [29] | Italy | Europe | Cohort | 361 | 243 (67.0) | 66 [54–78] | VDD<50 nmol/L | I-S-M | Yes |
Cereda et al. [30] | Italy | Europe | Cohort | 129 | 70 (54.3) | 77 [65–85] | VDD<20 ng/mL | S-M | Yes |
VDIS<30 ng/mL | |||||||||
D’Avolio et al. [21] | Switzerland | Europe | Case-control | 1,484 | 682 (45.9) | NR | NR | I | No |
Darling et al. [22] | UK | Europe | Case-control | 1,303 | 713 (54.7) | 57.7±8.7 | NR | I | No |
De Smet et al. [31] | Belgium | Europe | Cross-sectional | 2,903 | 1,108 (38.1) | NR | VDD<20 ng/mL | I-S | Yes |
Hastie et al. [23] | UK | Europe | Cohort | 341,484 | NR | NR | VDD<25 nmol/L | I-M | No |
VDIS<50 nmol/L | |||||||||
Hernández et al. [32] | Spain | Europe | Case-control | 413 | 253 (61.2) | NR | VDD<20 ng/mL | I-S-M | Yes |
Im et al. [24] | Korea | Asia | Case-control | 200 | 84 (42.0) | 52.3±20.3 | VDD<20 ng/dL | I-S | No |
Israel et al. [33] | Israel | Asia | Case-control | 576,455 | 271,601 (47.1) | NR | VDD<50 nmol/L | I | Yes |
Karahan and KatKat [34] | Turkey | Europe | Cross-sectional | 149 | 81 (54.3) | 63.5±15.3 | VDD<20 ng/mL | S-M | Yes |
VDIS<30 ng/mL | |||||||||
Katz et al. [25] | USA | America | Case-control | 987,849 | 455,458 (46.1) | NR | NR | I | No |
Li et al. [35] | UK | Europe | Case-control | 353,299 | 161,298 (45.6) | 67.7±8.1 | VDD<25 nmol/L | I-H-S | Yes |
VDIS<50 nmol/L | |||||||||
Livingston et al. [36] | UK | Europe | Cohort | 104 | 39 (37.5) | 68.5±18.3 | VDSL<34.4 nmol/L | I | Yes |
Luo et al. [37] | China | Asia | Cross-sectional | 895 | 405 (45.2) | NR | VDD<30 nmol/L | I-S-M | Yes |
Macaya et al. [38] | Spain | Europe | Cohort | 80 | 35 (43.7) | NR | VDD<20 ng/mL | S | Yes |
Maghbooli et al. [39] | Iran | Asia | Cross-sectional | 235 | 144 (61.3) | 58.7±15.2 | VDD<20 ng/mL | H-S-M | Yes |
VDIS<30 ng/mL | |||||||||
Mardani et al. [40] | Iran | Asia | Cross-sectional | 123 | 65 (52.8) | 42.1±14,9 | VDD<10 ng/mL | I | Yes |
VDIS<30 ng/mL | |||||||||
Meltzer et al. [41] | USA | America | Case-control | 489 | 123 (25.0) | 49.2±18.4 | VDD<20 ng/mL | I | Yes |
Mendy et al. [42] | USA | America | Cohort | 689 | 365 (53.0) | 49.5 [35.2–67.5] | NR | H-S | Yes |
Merzon et al. [43] | Israel | Asia | Case-control | 7,807 | 3,234 (41.4) | 41.4±NR | VDD<20 ng/mL | I-H | Yes |
VDIS<30 ng/mL | |||||||||
Panagiotou et al. [44] | UK | Europe | Cohort | 134 | 73 (54.4) | 68.7±14.0 | VDD<25 nmol/L | S | Yes |
VDIS<50 nmol/L | |||||||||
Radujkovic et al. [45] | Germany | Europe | Cohort | 185 | 95 (51.0) | 60 [49–70] | VDD<12 ng/mL | S-M | Yes |
VDIS<20 ng/mL | |||||||||
Vasiliou et al. [46] | Greece | Europe | Cohort | 39 | 31 (79.4) | 61.5±13.2 | VDD<20 ng/mL | H-M | Yes |
VDIS<30 ng/mL | |||||||||
Ye et al. [47] | China | Asia | Case-control | 142 | 55 (38.7) | NR [0.1-85] | VDD<50 nmol/L | I-S | Yes |
VDIS<75 nmol/L |
Study | Sample size in the study | Sample size included in meta-analyses |
Outcomes evaluated in the study | Outcomes evaluated in the meta-analyses | Findings in the study |
Limitations in extracting data | ||
---|---|---|---|---|---|---|---|---|
D-CIMA | D-CSMA | D-CMMA | ||||||
Abdollahi et al. [27] | 402 | 402 | – | – | I | I | I(+) | VDD was defined as <10 ng/mL, but the sample distribution for VDD was not suitable for statistical analysis; A statistical comparison was made for VDIS <30 ng/mL; Therefore, the data belonging to VDIS were included in the meta-analysis, and the measurement unit was assigned as “other” |
Baktash et al. [28] | 105 | – | – | 70 | I-M | M | I(+); M(-) | There was uncertainty in the definition of comparison groups for COVID-19 infection; We sent an email to the corresponding author, but we did not receive a reply; Therefore, COVID-19 infection data were not included in the D-CIMA |
Campi et al. [29] | 361 | 361 | 103 | 103 | I-S-M | I-S-M | I(+); S(+); M(+) | There was no limitation in data extraction |
Cereda et al. [30] | 129 | – | 129 | 129 | S-M | S-M | S(+); M(+) | The clinical outcomes were severe pneumonia, admission to the ICU, and in-hospital mortality; The ICU admission data were not appropriate for statistical analysis (0 observed cases); Therefore, we extracted data from severe pneumonia for the analysis of severity |
D’Avolio et al. [21] | 1,484 | – | – | – | I | – | I(+) | The definition of VDD was not available; There was no adequate information dealing with descriptive statistics; VDD was presented as median (IQR) and the findings were presented graphically; Since we extracted the data based on the number of cases, we did not include it in the meta-analysis In the study, the date of the data received from UK Biobank for the COVID-19 (-) control group was long ago; There was no VDD definition and they used quartile values of VDD; Since we extracted the data based on the number of cases, we did not include it in the meta-analysis |
Darling et al. [22] | 1,303 | – | – | – | I | – | I(-) | In the study, the date of the data received from UK Biobank for the COVID-19 (-) control group was long ago; There was no VDD definition and they used quartile values of VDD; Since we extracted the data based on the number of cases, we did not include it in the meta-analysis |
De Smet et al. [31] | 2,903 | 2,903 | 186 | – | I-S | I-S | I(+); S(+) | In the study, chest CT was performed for all COVID-19 patients to determine the disease stage; They classified the patients as stage 1 (early stage), stage 2 (progressive stage), and stage 3 (peak stage); We chose severe cases from stage 3 and non-severe cases from stage 1-2 |
Hastie et al. [23] | 341,484 | – | – | – | I-M | – | I(-); M(-) | There was no adequate information dealing with descriptive statistics; The findings were presented by using HR and IRR values; Since we extracted the data based on the number of cases, we did not include it in the meta-analysis |
Hernández et al. [32] | 413 | – | 197 | 197 | I-S-M | S-M | I(+); S(-); M(-) | For COVID-19 infection, VDD was presented as mean (±SD); Since the number of cases was not reported, we could not include it in D-CIMA |
Im et al. [24] | 200 | – | – | – | I-S | – | I(+); S(+) | In the study, the unit of ng/dL was used for laboratory measurements of serum 25(OH)D levels, and VDD was defined as 25(OH)D<20 ng/dL; We converted 20 ng/dL to 0.2 ng/mL; Since we thought there was an inconsistency, we could not include these data in the meta analyses |
Israel et al. [33] | 576,455 | 187,234 | – | – | I | I | I(+) | Age matching was performed between the case and control groups, but single summary statistics for the population were not presented |
Karahan and Katkat [34] | 149 | – | 149 | 149 | S-M | S-M | S(+); M(+) | There was no limitation in data extraction |
Katz et al. [25] | 987,849 | – | – | – | I | – | I(+) | There was no adequate information dealing with descriptive statistics; The findings were presented as ORs; Since we extracted the data based on the number of cases, we did not include it in the meta-analysis |
Li et al. [35] | 353,299 | 3,502 | 1,082 | – | I-H-S | I-S | I(+); H(+); S(+) | This study defined hospitalization as one record of origin (whether the patient s tested positive or not); In the study, hospitalized, confirmed, and severe COVID-19 cases were compared with community controls; We think that this study design is inappropriate; For this reason, we extracted data on infections from patients who presented to the hospital with suspected COVID-19 and confirmed COVID-19, and for the severity from patients with confirmed and severe COVID-19 |
Livingston et al. [36] | 104 | 104 | – | – | I | I | I(-) | The definition of VDD was not available; Statistical comparisons were performed for 25(OH)D <34.4 nmol/L; Therefore, the data belonging to this distinction were included in the meta-analysis, and the measurement unit was assigned as “other” |
Luo et al. [37] | 895 | 895 | 335 | 74 | I-S-M | I-S-M | I(+); S(+); M(-) | There was no limitation in data extraction |
Macaya et al. [38] | 80 | – | 80 | S | S | S(+) | There was no limitation in data extraction | |
Maghbooli et al. [39] | 235 | – | 235 | 235 | H-S-M | S-M | H(+); S(+); M(+) | There was no limitation in data extraction; Although the authors defined VDD as 25(OH)D<20 ng/mL, the dataset that could be extracted from the article belonged to the category of 25(OH)D<30 ng/mL; Therefore, it was included in the overall analysis |
Mardani et al. [40] | 123 | 123 | – | – | I | I | I(+) | We extracted data from their supplementary file according to 25(OH)D<20 ng/mL |
Meltzer et al. [41] | 489 | 489 | – | – | I | I | I(+) | There was no limitation in data extraction |
Mendy et al. [42] | 689 | – | 689 | – | H-S | S | H(+); S(+) | The definition of VDD was not available; Therefore, the measurement unit was assigned as “other” in the D-CSMA |
Merzon et al. [43] | 7,807 | 7,807 | – | – | I-H | I | I(+); H(+) | There was no limitation in data extraction |
Panagiotou et al. [44] | 134 | – | 134 | – | S | S | S(+) | The authors classified the patients as admitted to the ITU and non-ITU wards; |
When we extracted data, we chose patients admitted to non-ITU wards as non-severe and those admitted to ITU wards as severe; A statistical comparison was made for VDIS <50 nmol/L; Therefore, the data belong to VDIS were included in the D-CSMA | ||||||||
Radujkovic et al. [45] | 185 | – | 185 | – | S-M | S | S(+); M(+) | The authors classified patients as inpatients and outpatients; When we extracted data, we chose the outpatients as non-severe and the inpatients as severe according to their definition |
Vassiliou et al. [46] | 39 | – | – | 39 | H-M | M | H(-); M(-) | There was no limitation in data extraction |
Ye et al. [47] | 142 | 142 | 60 | – | I-S | I-S | I(+); S(+) | There was no limitation in data extraction |
Total | 2,277,860 | 203,962 | 3,564 | 996 |
Meta-analyses | Publication bias |
Heterogeneity |
Quantifying heterogeneity |
Findings of meta-analyses |
|
---|---|---|---|---|---|
Egger test (p-value) | Cochran Q test (p-value) | I2 (95% CI), %/τ2 (95% CI) | Peto random-effect model |
||
OR (95% CI) | p-value | ||||
D-CIMA for serum 25(OH)D levels <20 ng/mL and 50 nmol/L | 0.399 | <0.001 | 85.4 (73.2, 92.1)/0.06 (0.05, 1.02) | 1.64 (1.32, 2.04) | <0.001 |
D-CIMAOverall for serum 25(OH)D levels with all different measurement units | 0.091 | <0.001 | 87.0 (78.7, 92.1)/0.08 (0.06, 0.76) | 1.86 (1.51, 2.30) | <0.001 |
D-CSMA for serum 25(OH)D levels <20 ng/mL and 50 nmol/L | 0.064 | <0.001 | 91.5 (86.1, 94.8)/1.18 (0.47. 5.29) | 2.42 (1.13, 5.17) | 0.022 |
D-CSMAOverall for serum 25(OH)D levels with all different measurement units | 0.017 | <0.001 | 92.8 (90.2, 94.7) |
1.24 (0.71, 2.17)1 | 0.445 |
D-CMMA for serum 25(OH)D levels <20 ng/mL and 50 nmol/L | 0.911 | <0.001 | 82.6 (60.1, 92.4)/1.30 (0.12, 10.51) | 1.64 (0.53, 5.06) | 0.390 |
D-CMMAOverall for serum 25(OH)D levels with all different measurement units | 0.909 | 0.001 | 70.8 (39.7, 85.9)/0.71 (0.00, 3.02) | 1.58 (0.76, 3.27) | 0.211 |
SD, standard deviation; Min, minimun; Max, maximun; IQR, interquartile range; NR, not reported; VDD, vitamin D deficiency; VDIS, vitamin D insufficiency; VDSL, vitamin D serum level; H, hospitalization; I, COVID-19 infection; S, severity; M, mortality.
COVID-19, coronavirus disease 2019; D-CIMA, vitamin D and COVID-19 infection meta-analysis; D-CSMA, vitamin D and COVID-19 severity meta-analysis; D-CMMA, vitamin D and COVID-19 mortality meta-analysis; I, COVID-19 infection; S, severity; M, mortality; H, hospitalization; VDD, vitamin D deficiency; ICU, intensive care unit; IQR, interquartile range; CT, computed tomography; HR, hazard ratio; IRR, incidence rate ratio; SD, standard deviation; OR, odds ratio; ITU, intensive therapy unit; VDIS, vitamin D insufficiency. (+), indicates that the association of low levels of vitamin D and I, S, M and H was statistically significant; (-) indicates that the association of low levels of vitamin D and I, S, M and H was not statistically significant.
D-CIMA, vitamin D and COVID-19 infection meta-analysis; D-CSMA, vitamin D and COVID-19 severity meta-analysis; D-CMMA, vitamin D and COVID-19 mortality meta-analysis; COVID-19, coronavirus disease 2019; OR, odds ratio; CI, confidence interval. Trim-and-fill method applied.