An analysis conducted by researchers at the University of Turku and Turku University Hospital in Finland has suggested that obstructive sleep apnea (OSA) may be a risk factor for severe coronavirus disease 2019 (COVID-2019).
The team found that a disproportionate number of patients admitted to hospital with COVID-19 had pre-existing OSA (diagnosed a median of 2.5 years beforehand).
The researchers also identified elevated levels of C-reactive protein (CRP), procalcitonin (PCT), and possibly reduced oxygen saturation as potentially useful measures for predicting which patients may require critical care.
A pre-print version of the paper is available on medRxiv*, while the article undergoes peer review.
COVID-19 in Finland
Since the COVID-19 outbreak has rapidly spread across the world, Southwest Finland has been relatively unaffected.
When the World Health Organization (WHO) reported more than 1,500,000 cases in just Europe alone by May 3rd, Southwest Finland, with its population of almost 480,000, had only identified 263 cases.
Of those cases, 28 had been admitted to the Turku University Hospital.
Initial risk factors to be identified
During the first phase of the outbreak, old age, cardiovascular disease, and hypertension were among the first factors to be identified as increasing the risk of severe disease and death. Obesity had also been recognized as a factor predisposing to disease that would require critical care.
Researchers have proposed several mechanisms underlying the association between these conditions and severe COVID-19. These have included chronic inflammation, hypoxemia, oxidative stress, and the influence of the renin-angiotensin-aldosterone system (RAAS) on levels of angiotensin-converting enzyme 2 (ACE2). ACE2 is the receptor that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses to gain entry to host cells.
However, the involvement of these mechanisms has not yet been resolved.
What did the current study involve?
Now, Thijs Feuth and colleagues have analyzed baseline characteristics, as derived from hospital record data, among all 28 patients with COVID-19 that had been admitted to Turku University Hospital by May 3rd.
Common clinical features among patients were fever, hypoxemia, raised CRP, elevated PCT, and lymphotycemia.
Common pre-existing health conditions were hypertension (43%), obesity (35%), OSA (29%), diabetes (25%), asthma (14%), active malignant disease (11%) and chronic obstructive pulmonary disorder (7%).
Comparing patients who required critical care with those who did not
Seven patients required treatment in the intensive care unit (ICU), the baseline characteristics of whom were compared with the remaining 21 who did not.
Baseline CRP and PCT levels were significantly higher among the ICU group than among the non-ICU group, at medians of 187 mg/L and 0.46 µg/L versus 52 mg/L and 0.12 µg/L.
A trend towards lower oxygen saturation was also observed among the ICU group, compared with the non-ICU group, at 87% versus 93%.
The high prevalence of OSA
The researchers point out that in the Hospital District of Southwest Finland, a total of 12,799 people use continuous positive airway pressure therapy for OSA, and around 2,000 people use a mandibular advancement device.
“Thus, the prevalence of hospital-treated OSA is around 3.1%,” writes the team.
Given, the disproportionately high prevalence of pre-existing OSA (29%) among the patients, Feuth, and colleagues further analyzed their clinical characteristics.
Body mass index (BMI) was more than 30 kg/m2 in 75% of cases (overall median 38 kg/m2), meaning that most of these patients were severely obese.
“Even though obesity is by now an established risk factor for severe COVID-19, the weight alone does not explain the high proportion of patients with OSA, as obesity is a much more common pre-existing condition than OSA in the Finnish population with a prevalence of 26.1% among men and 27.5% among women,” write the researchers.
Other features of OSA that the team suggest may explain the increased risk of severe COVID-19 are intermittent hypoxia, which could exacerbate the hypoxia caused by COVID-19, and chronic inflammation, which could contribute to the “cytokine storm syndrome” that can be fatal in cases of COVID-19.
Furthermore, OAS could influence the RAAS and, therefore, the regulation of ACE2 expression.
What do the authors say about their findings?
Regarding the higher level of CRP among those in the ICU group, the authors suggest that this could be linked to the pulmonary damage that COVID-19 causes. However, blood cultures and radiology findings did not reveal any cases of infections such as pneumonia.
The authors say their findings suggest that high CRP, PCT, and possibly oxygen saturation could be useful clinical measures for identifying patients who may require critical care. If this is confirmed in more extensive studies, the measures may be useful for triage, particularly if the epidemic is out of control, and there is a shortage of hospital places.
Finally, the authors say the disproportionate prevalence of pre-existing OSA among the patients may have important implications for individual risk assessment, as well as in helping to shed light on the pathogenesis of severe COVID-19.
“The question of whether OSA is an independent risk factor should be addressed in larger cohorts,” concludes the team.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.