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In the context of coronavirus disease 2019 (COVID-19), underlying health conditions such as lung disease, diabetes, hypertension, and cardiovascular disease confer an increased risk of infection and associated adverse outcomes including admission to the intensive care unit (ICU) and death. Additionally, the authors of several recently published papers have proposed that obstructive sleep apnea (OSA) may represent another important variable contributing to increased risk related to COVID-19.1,2
In 2 small studies of individuals admitted to the ICU with confirmed COVID-19, researchers reported that OSA was present in 21.0% and 28.6% of patients, respectively.3,4 Such findings suggest that OSA “could potentially contribute to worsening hypoxemia and the cytokine storm that occurs in COVID patients,” wrote the authors of an article published in the Journal of Clinical Sleep Medicine (JCSM).2
However, the mechanisms potentially linking to OSA to worse outcomes in COVID-19 remain to be identified, according to coauthor Atul Malhotra, MD, a board-certified pulmonologist, intensivist, professor of medicine, and research chief of pulmonary, critical care, and sleep medicine at the University of California, San Diego School of Medicine. “Some studies have suggested that sleep apnea is a risk factor for pneumonia, and sleep deprivation — even without sleep apnea — has been associated with risk of developing pneumonia and with impaired response to vaccinations,” Dr Malhotra noted.5,6
One area that warrants special attention in future research is the role of the immune system in OSA, and there is a need for additional investigation regarding the benefits of OSA treatment from the standpoint of respiratory infection, noted Dr Malhotra. “Trying to separate the effects of obesity, diabetes, and sleep apnea will likely require interventional studies — these can be difficult to differentiate since they are all correlated.”
In a commentary published in JCSM, Cristina Salles, MD, PhD, and Hayssa Mascarenhas Barbosa, MSc, of the Bahiana School of Medicine and Public Health in Salvador, Brazil, also pointed to the need for research elucidating the degree of OSA-related sleep deprivation that would be required to exacerbate the pulmonary inflammatory process in COVID-19.7
We checked in with Dr Salles to learn more about the possible role of OSA in COVID-19 outcomes.
What is known or suspected thus far regarding OSA as a risk factor for COVID-19 infection and illness severity?
When COVID-19 emerged, I raised some questions about the possibility of associations between immunity, sleep, and COVID-19. Looking for data in the medical literature, I found several articles, including a study by Nunes et al that addressed immunity, sleep, and lung inflammation.8 The authors observed that mice suffering from sleep deprivation had a higher inflammatory process in the airways than mice with healthy sleep.
This study was important because it provided information to continue hypothesizing on a scientific basis, so I made a publication posing the question of whether sleep deprivation would have a negative effect on the lung condition of patients with COVID-19.9
Later, noting that patients with OSA can also have sleep deprivation, I collaborated with Barbosa and we wondered whether sleep deprivation as a consequence of OSA would be a conducive condition for the pulmonary inflammatory process in COVID-19 patients.7
Similar questions have begun to emerge in the medical literature. McSharry and Malhotra pointed out that the 2 conditions share common comorbidities — obesity, asthma, diabetes, hypertension, cardiovascular disease, and chronic obstructive pulmonary disease.2 Moreover, in this same study, the authors questioned the possibility of OSA contributing to the aggravation of hypoxemia in patients with COVID-19 considering that obesity hypoventilation and OSA are related to hypoxemia, which can be an aggravating factor in the hypoxemia of COVID-19 pneumonia.
Parallel to the questions mentioned earlier, the hypotheses regarding sleep deprivation, OSA, and COVID-19 began to produce results from field research. Bhatraju et al evaluated 24 patients with COVID-19 in an ICU in Washington State, and they revealed that 21% had OSA.4 Additionally, Arentz et al evaluated 21 patients with COVID-19 in an ICU and observed that 28.6% had comorbid OSA.5
Since the pandemic emerged, what has been the role of clinicians who treat OSA patients?
Based on the hypotheses proposed above, we expected sleep medicine specialists to work in parallel with the evolution of COVID-19 infection; however, this has not happened. Grote et al observed that sleep medicine services were reduced by almost 80% during the first 1 to 2 months of the pandemic in Europe.10 These authors drew attention to the need for the sleep medicine community to collaborate in the improvement of strategies to assist patients with sleep-disordered breathing during significant events such as the COVID-19 pandemic.
What should be the main focus of research pertaining to this topic?
SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] is still a new pathogen requiring further studies. We need research with a greater number of individuals to determine the possible effect of OSA on patients with COVID-19, thus creating a more solid basis for strategic therapeutic decisions.
References
1. Tufik S, Gozal D, Ishikura IA, Pires GN, Andersen ML. Does obstructive sleep apnea lead to increased risk of COVID-19 infection and severity? J Clin Sleep Med. Published online May 22, 2020. doi:10.5664/jcsm.8596
2. McSharry D, Malhotra A. Potential influences of obstructive sleep apnea and obesity on COVID-19 severity. J Clin Sleep Med. Published online May 1, 2020. doi:10.5664/jcsm.8538
3. Bhatraju PK, Ghassemieh BJ, Nichols M, et al. COVID-19 in critically ill patients in the Seattle region – case series. N Engl J Med. 2020;382(21):2012-2022.
4. Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA. 2020;323(16):1612-1614.
5. Su VY-F, Liu CJ, Wang HK, et al. Sleep apnea and risk of pneumonia: a nationwide population-based study. CMAJ. 2014;186(6):415-421.
6. Taylor DJ, Kelly K, Kohut ML, Song KS. Is insomnia a risk factor for decreased influenza vaccine response? Behav Sleep Med. 2017;15(4):270-287.
7. Salles C, Barbosa HM. COVID-19 and obstructive sleep apnea. J Clin Sleep Med. Published online June 2, 2020. doi:10.5664/jcsm.8606
8. Nunes JOF, Apostolico JS, Andrade DAG, et al. Sleep deprivation predisposes allergic mice to neutrophilic lung inflammation. J Allergy Clin Immunol. 2018;141(3):1018-1027.
9. Salles C. Correspondence COVID-19: Melatonin as a potential adjuvant treatment. Life Sci. 2020;253:117716. doi:10.1016/j.lfs.2020.117716
10. Grote L, McNicholas WT, Hedner J. Sleep apnoea management in Europe during the COVID-19 pandemic: data from the European Sleep Apnoea Database (ESADA). Eur Respir J. 2020;55(6):2001323.
