3 Results
3.1 Bidirectional
two-sample MR between the allergic disease and COVID-19
74 and 73 IVs were selected for the
two-sample MR analysis of the allergic disease on SARS‐CoV‐2 infection
and severe COVID‐19, respectively. In addition, 19 and 31 IVs were
selected for MR analysis of SARS-CoV-2 infection and severe COVID-19 on
the allergic disease, respectively. (Figure 2) The characteristics of
IVs were presented in Supplementary Tables 1 to 4
in the order shown in Figure 2.
The allergic disease was not
causally associated with SARS‐CoV‐2
infection (P=0.545; OR=0.99; 95%
CI: 0.97-1.02) but have a causal and protective effect on severe
COVID-19 (P=0.028; OR=0.91; 95% CI: 0.83-0.99). In the analysis of the
effect of allergic disease on severe COVID-19, the four methods were in
the same direction. The heterogeneity test indicated a minor problem
(P=0.001) but no significant pleiotropy was observed (P=0.691). In
contrast, no significant causal effect was found of SARS-CoV-2
infection/severe COVID-19 on the allergic
disease. Incidentally, horizontal
pleiotropy was not detected (all P >0.05) in any of the
above analyses. (Figures 2 and 4)
3.2 Univariate MR between
the various allergic diseases and severe COVID-19
The numbers of selected IVs were listed in Figure 3, with specific
characteristics (including F values) described in Supplementary Tables 5
to 12 in the order shown in Figure 3. AD showed a clear causal
relationship with severe COVID-19
(P=0.019; OR=0.94; 95% CI: 0.88-0.99). No significant pleiotropy or
heterogeneity was observed (P=0.343 and 0.617, respectively). (Figures 3
and 4)
Although no causal relationship between asthma and severe COVID-19 was
observed in univariate MR analysis (P=0.424; OR=0.97; 95% CI:
0.91-1.04), the analysis of each asthma subtype showed positive results:
mixed asthma (P=0.007; OR=0.97; 95%
CI: 0.94-0.99) and childhood asthma (age<16 years old)
(P=0.017; OR=0.90; 95% CI:
0.83-0.98) were causal protective factors for severe COVID-19.
Heterogeneity and horizontal pleiotropy were not observed in the
analyses of both mixed asthma (P= 0.559 and 0.718, respectively) and
childhood asthma (P= 0.111 and 0.896, respectively). (Figures 3 and 4)
Additionally, the univariate MR analysis of doctor-confirmed
hay fever, AR, or eczema exhibited
an ambiguous result: a positive protective result (P=0.035; OR=0.935;
95% CI: 0.878-0.995) was obtained using the primary method (IVW), and
the directions of MR Egger and weighted median were consistent on the
left, but the direction of weighted mode was not.
There was small heterogeneity
(P=0.008) but no horizontal pleiotropy (P=0.420) in this analysis.
The robustness of these univariate MR results was further proved by the
insignificant MR-Egger intercepts (all P>0.05), implying
the absence of horizontal pleiotropy. (Figure 3)
3.3 Multivariate
MR of three allergic diseases and fourasthma subtypes
The results of the multivariate MR analysis between the three allergic
diseases (AR, AD, and asthma) and
severe COVID-19 were shown in Figure 5. In the multivariate MR analysis
with AR, AD, and asthma adjusted for each other, asthma was surprisingly
found to be a suggestive major causal protective factor against severe
COVID-19 (P=0.024; OR=0.90; 95% CI: 0.83-0.98).
Figure 6 displayed the outcomes of
multivariate MR analysis between four types of asthma (allergic,
non-allergic, mixed, and childhood asthma) and severe COVID-19. Only
childhood asthma remained suggestively causally associated with severe
COVID-19 (P=0.048; OR=0.770; 95% CI: 0.594-0.998).