Aging and obesity-related conditions seem to worsen the effect of Coronavirus Disease 2019 (COVID-19). This study assessed the possible roles of metabolic/obesity phenotypes and vitamin D status in increasing the greater severity of COVID-19. We studied 353,299 UK Biobank participants from England with a mean age of 67.7 years. Metabolic/obesity phenotypes were defined as a combination of metabolic components (hypertension, high cholesterol, and diabetes) and obesity. Multivariate logistic regression analysis was performed to test whether the addition of metabolic disorders and vitamin D insufficiency increased obesity associations with COVID-19 hospitalization, confirmed COVID-19, and severe COVID-19. Metabolically unhealthy obesity (MUHO) represented 12.3% of the total analytic samples, and 21.5%, 18.5%, and 19.8% of the included subpopulations with COVID-19 hospitalization, confirmed COVID-19, and severe COVID-19, respectively. Vitamin D insufficiency phenotypes represented 53.5% of the total analytic samples, and 59.5%, 61.7%, and 61.5% of the included subpopulations with COVID-19 hospitalization, confirmed COVID-19, and severe COVID-19, respectively. In multivariate logistic regression, MUHO and vitamin D insufficiency and their combination were significantly associated with COVID-19 illness severity (odds ratio [OR] for COVID-19 hospitalization = 2.33, 95% confidence interval [CI], 2.02-2.70; OR for confirmed COVID-19 = 2.06, 95% CI, 1.58-2.70; OR for severe COVID-19 = 2.06, 95% CI, 1.47-2.87). Elderly men were prone to have a higher risk of COVID-19 than women. Our findings showed that MUHO and vitamin D insufficiency are associated with a significantly increased risk of COVID-19 severity, especially for adults 65 years and older. Susceptible individuals should be aware of their conditions and avoid contact with new coronavirus.
Figure 1. Association between (A) vitamin D insufficiency and (B) vitamin D deficiency (as exposure variable) and reported COVID-19 outcomes (as outcome) by subgroup analysis. The analysis used univariate logistic regression models. Abbreviations: COVID-19, Coronavirus Disease 2019; BMI, body mass index; CI, confidence interval; MHNW, metabolically healthy normal weight; MHO, metabolically healthy obesity; MHOW, metabolically healthy overweight; MUHNW, metabolically unhealthy normal weight; MUHO, metabolically unhealthy obesity; MUHOW, metabolically unhealthy overweight; TDI, Townsend deprivation index.
Model adjusted†
COVID-19 hospitalization
Confirmed COVID-19
Severe COVID-19
OR (95% CI)
Difference in OR, %
OR (95% CI)
Difference in OR, %
OR (95% CI)
Difference in OR, %
Non metabolic & vitamin D status adjusted
1.56 (1.42, 1.70)
Ref.
1.48 (1.25, 1.74)
Ref.
1.53 (1.25, 1.88)
Ref.
Metabolic status adjusted
1.44 (1.31, 1.58)
7.7
1.39 (1.18, 1.65)
6.1
1.43 (1.16, 1.76)
6.5
Vitamin D status adjusted
1.50 (1.36, 1.64)
3.8
1.43 (1.22, 1.69)
3.4
1.49 (1.21, 1.83)
2.6
Both metabolic & vitamin D status adjusted
1.38 (1.26, 1.52)
11.5
1.35 (1.14, 1.60)
8.8
1.39 (1.12, 1.71)
9.2
Table 2 Comparison of multivariable ORs for obesity vs. normal-weight level of BMI for COVID-19, without and with adjustment for metabolic or vitamin D status.
Characteristics
Vitamin D deficiency (< 25 nmol/L)
Vitamin D insufficiency (< 50 nmol/L)
No
Yes
No
Yes
OR (95% CI)†
P
OR (95% CI)†
P
OR (95% CI)†
P
OR (95% CI)†
P
COVID-19 hospitalization
MHNW
1 (Ref.)
1.24 (0.98, 1.57)
0.071
1 (Ref.)
1.24 (1.06, 1.45)
0.007
MHOW
1.14 (1.02, 1.27)
0.024
1.27 (1.03, 1.58)
0.027
1.20 (1.03, 1.40)
0.021
1.30 (1.12, 1.50)
<0.001
MHO
1.22 (1.06, 1.40)
0.006
1.77 (1.42, 2.22)
<0.001
1.23 (0.99, 1.52)
0.058
1.53 (1.30, 1.81)
<0.001
MUHNW
1.21 (1.02, 1.42)
0.024
1.52 (1.06, 2.18)
0.024
1.21 (0.98, 1.51)
0.079
1.49 (1.20, 1.84)
<0.001
MUHOW
1.36 (1.21, 1.54)
<0.001
1.97 (1.59, 2.46)
<0.001
1.33 (1.13, 1.58)
0.001
1.76 (1.50, 2.05)
<0.001
MUHO
1.91 (1.69, 2.15)
<0.001
2.46 (2.05, 2.94)
<0.001
1.88 (1.58, 2.24)
<0.001
2.33 (2.02, 2.70)
<0.001
Confirmed COVID-19
MHNW
1 (Ref.)
0.93 (0.60, 1.44)
0.734
1 (Ref.)
1.11 (0.84, 1.47)
0.474
MHOW
1.31 (1.08, 1.59)
0.007
1.09 (0.75, 1.59)
0.657
1.34 (1.02, 1.75)
0.034
1.38 (1.07, 1.79)
0.015
MHO
1.42 (1.12, 1.80)
0.004
1.34 (0.89, 2.01)
0.167
1.02 (0.68, 1.52)
0.937
1.73 (1.31, 2.29)
<0.001
MUHNW
1.31 (0.97, 1.77)
0.078
2.21 (1.29, 3.78)
0.004
1.33 (0.89, 1.98)
0.168
1.71 (1.18, 2.48)
0.005
MUHOW
1.41 (1.12, 1.77)
0.003
1.72 (1.15, 2.57)
0.009
1.34 (0.98, 1.84)
0.065
1.70 (1.28, 2.26)
<0.001
MUHO
1.68 (1.34, 2.11)
<0.001
2.34 (1.69, 3.23)
<0.001
1.63 (1.16, 2.28)
0.004
2.06 (1.58, 2.70)
<0.001
Severe COVID-19
MHNW
1 (Ref.)
1.05 (0.61, 1.81)
0.866
1 (Ref.)
1.00 (0.69, 1.45)
0.996
MHOW
1.32 (1.03, 1.70)
0.031
1.35 (0.86, 2.12)
0.196
1.27 (0.90, 1.79)
0.173
1.36 (0.98, 1.88)
0.067
MHO
1.42 (1.04, 1.93)
0.027
1.90 (1.19, 3.03)
0.007
0.99 (0.60, 1.65)
0.976
1.75 (1.24, 2.49)
0.002
MUHNW
1.38 (0.96, 2.00)
0.085
2.43 (1.29, 4.59)
0.006
1.37 (0.85, 2.22)
0.195
1.65 (1.04, 2.60)
0.033
MUHOW
1.58 (1.19, 2.09)
0.001
1.86 (1.15, 3.02)
0.012
1.35 (0.92, 1.97)
0.125
1.82 (1.29, 2.57)
0.001
MUHO
1.82 (1.37, 2.41)
<0.001
2.48 (1.66, 3.70)
<0.001
1.68 (1.12, 2.52)
0.012
2.06 (1.47, 2.87)
<0.001
Table 3 Joint associations of metabolic/obesity phenotypes and vitamin D status with COVID-19 outcomes.
Figure 2. Associations of metabolic/obesity phenotypes and vitamin D status with COVID-19 outcomes stratified by (A) sex and (B) age subgroups. The models adjusted for age, Townsend deprivation index, qualifications, employment, ethnicity, and smoking status. Abbreviations: COVID-19, Coronavirus Disease 2019; MHNW, metabolically healthy normal weight; MHO, metabolically healthy obesity; MHOW, metabolically healthy overweight; MUHNW, metabolically unhealthy normal weight; MUHO, metabolically unhealthy obesity; MUHOW, metabolically unhealthy overweight.
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