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Severe COVID-19 Could Potentially Lead to Obstructive Sleep Apnea

In a bidirectional Mendelian randomization analysis, findings revealed an association with obstructive sleep apnea and severe COVID-19 that were suggestive of a causal relationship.

In a recent analysis, data showed a relationship between severe COVID-19 and obstructive sleep apnea (OSA), marking this as the first study that clarifies the relationship between OSA and the risk of COVID-19 using a bidirectional, 2-sample Mendelian randomization (MR) analysis.1 This study also provides a better understanding of OSA and COVID-19 as it is important for the prevention of disease and the development of therapeutic approaches.

The inverse-variance weighted (IVW) mode in the MR analysis demonstrated that COVID-19 had a correlation with a 4.9% higher risk of OSA (OR, 1.049; 95% CI, 1.018-1.081; P = .002), which was consistent in the MR pleiotropy residual sum and outlier (MR-PRESSO) (OR, 1.049; 95% CI, 1.018-1.081; P = .004), weighted median (OR, 1.048; 95% CI, 1.003-1.095; P = .035), and the MR-Egger regression (OR, 1.083; 95% CI, 1.012-1.190; P = .041).1

Study investigator Xiang Gao, MD, department of otolaryngology head and neck surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, and colleagues wrote, “There is no significant evidence supporting a causal association between OSA and any COVID phenotype, while we identified potential evidence for a causal effect of severe COVID-19 on an increased risk of OSA.”

In the evaluation of the causal relationship between OSA and COVID-19, the MR was used and selected single-nucleotide polymorphisms for the instrumental variables that came from genome-wide association studies. The IVW method was selected as the main approach for data analysis to estimate the possible causal effects whereas the MR-Egger and the MR-PRESSO were used for a sensitivity analysis that would produce the robustness of the results.

The findings from the MR analyses also showed no statistically significant evidence with the IVW mode for the causal relationship between OSA and COVID-19 (OR, 0.984; 95% CI, 0.764-1.268; P = .903), hospitalized COVID-19 vs. non-hospitalized COVID-19 (OR, 1.233; 95% CI, 0.756-2.012; P = .401), hospitalized COVID-19 vs. the general population (OR, 0.945; 95% CI, 0.704-1.269; P = .708), or severe COVID-19 (OR, 0.726; 95% CI, 0.471-1.121; P =.149).1 In hospitalized and nonhospitalized patients with COVID-19, the results did not display a difference for OSA susceptibility. Notably, there was also nothing shown in the results that genetic susceptibility to OSA would increase the risk of COVID-19, although an increased risk of OSA was associated with genetic susceptibility to severe COVID-19.

“According to our results, severe COVID-19 is causally related with OSA, shedding fresh light on the mechanisms underlying the relationship between OSA and COVID-19. Importantly, it may have indications for clinicians to pay more attention to the OSA-monitoring and potential comorbidity therapy such as airway management among severe COVID-19 patients, as they are more likely to fail extubation and require prolonged mechanical ventilation,” Gao et al noted.1

A strength of this study is that the MR approach had the ability to show a powerful causal relationship between the OSA and COVID-19,1 with this approach being previously validated for the demonstration of such relationahips.2 The MR approach also guaranteed the inference of the 2 diseases from both directions which was able to avoid any misleading causal effects.3 On the other hand, the limitations of the analysis included a biased estimation of causal inference and whether the results can be generalized for other populations of different demographics and sizes. Another limitation is that results were influenced by a weak instrument bias. Additionally, the findings show a relationship between OSA and COVID-19 over a lifetime effect, even though the risk of having OSA could be based on time because of age.

Gao et al noted, “Our MR study did not find genetic predisposition to OSA traits would alter the susceptibility to SARS-CoV-2 infection, COVID-19 hospitalization, or severe. Novelly and unexpectedly, genetic susceptibility to severe respiratory-confirmed COVID-19 was causally associated with increased risk of OSA in IVW mode, implying that OSA surveillance should be intensified in severe respiratory-verified COVID-19 patients.”

REFERENCES
1. Gao X, Wei T, Wang H, et al. Causal associations between obstructive sleep apnea and COVID-19: A bidirectional Mendelian randomization study. Sleep Med. 2022;101:28-35. doi:10.1016/j.sleep.2022.09.013
2. Sonti S, Grant SFA. Leveraging genetic discoveries for sleep to determine causal relationships with common complex traits. Sleep. 2022;45(10):zsac180. doi:10.1093/sleep/zsac180
3. Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014;23(R1):R89-R98. doi:10.1093/hmg/ddu328