Silent hypoxia in COVID-19: pathomechanism and possible management strategy

Rahman, Ahsab; Tabassum, Tahani; Araf, Yusha; Nahid, Abdullah Al; Ullah, Asad; Hosen, Mohammad Jakir

doi:10.1007/s11033-021-06358-1

Cited by 124 publications

(102 citation statements)

References 31 publications

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“…Messineo et al, found that greater breath-hold induced desaturation–indicative for gas exchange deficit–was associated with COVID-19 severity [ 26 ]. Secondly, an inadequate ventilatory control, in the case of silent hypoxia has also been reported to be a risk factor for COVID-19 severity [ 27 ]. Likewise, patients with OSA could be predisposed to have a more tolerable lower oxygen saturation level without dyspnea, until they are infected with SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

Association between the degree of obstructive sleep apnea and the severity of COVID-19: An explorative retrospective cross-sectional study

Donders

Zhou

et al. 2021

PLoS ONE

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Obstructive sleep apnea (OSA) on its own, as well as its risk factors, have been found to be associated with the outcome of Coronavirus disease 2019 (COVID-19). However, the association between the degree of OSA and COVID-19 severity is unclear. Therefore, the aim of the study was to evaluate whether or not parameters to clinically evaluate OSA severity and the type of OSA treatment are associated with COVID-19 severity. Patient data from OSA patients diagnosed with COVID-19 were reviewed from outpatients from the Isala Hospital and patients admitted to the Isala Hospital, starting from March until December 2020. Baseline patient data, sleep study parameters, OSA treatment information and hospital admission data were collected. Apnea hypopnea index (AHI), low oxyhemoglobin desaturation (LSAT), oxygen desaturation index (ODI), respiratory disturbance index (RDI), and the type of OSA treatment were regarded as the independent variables. COVID-19 severity–based on hospital or intensive care unit (ICU) admission, the number of days of hospitalization, and number of intubation and mechanical ventilation days–were regarded as the outcome variables. Multinomial regression analysis, binary logistic regression analysis, and zero-inflated negative binomial regression analysis were used to assess the association between the parameters to clinically evaluate OSA severity and COVID-19 severity. A total of 137 patients were included. Only LSAT was found to be significantly associated with the COVID-19 severity (p<0.05) when COVID-19 severity was dichotomized as non-hospitalized or hospitalized and ICU admission or death. Therefore, our findings showed that LSAT seems to be a significant risk factor for COVID-19 severity. However, the degree of OSA–based on AHI, ODI, and RDI–and OSA treatment were not found to be risk factors for COVID-19 severity when looking at hospital or ICU admission, the number of days of hospitalization, and number of intubation and mechanical ventilation days.

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Section: Discussionmentioning

confidence: 99%

Association between the degree of obstructive sleep apnea and the severity of COVID-19: An explorative retrospective cross-sectional study

Donders

Zhou

et al. 2021

PLoS ONE

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“…Two major complications in hospitalized COVID-19 patients are low blood oxygen and respiratory distress, also called silent hypoxia. It is suggested that silent hypoxia in patients with COVID-19 is multifactorial: (i) the hypoxia inducible factor (HIF) transcription factor responsible for inducing cellular responses to hypoxia also increases ACE-2 expression that can facilitate entry of the virus into cells; and (ii) hypoxia leads to more severe tissue damage by contributing to the “cytokine storm” and endothelial damage ( 86 ). These factors combined lead to severe tissue damage and are a major cause of death resulting from COVID-19.…”

Section: Risk Factors That Exacerbate Ototoxicitymentioning

confidence: 99%

Detecting Novel Ototoxins and Potentiation of Ototoxicity by Disease Settings

Coffin

Boney²,

Hill

et al. 2021

Front. Neurol.

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Over 100 drugs and chemicals are associated with permanent hearing loss, tinnitus, and vestibular deficits, collectively known as ototoxicity. The ototoxic potential of drugs is rarely assessed in pre-clinical drug development or during clinical trials, so this debilitating side-effect is often discovered as patients begin to report hearing loss. Furthermore, drug-induced ototoxicity in adults, and particularly in elderly patients, may go unrecognized due to hearing loss from a variety of etiologies because of a lack of baseline assessments immediately prior to novel therapeutic treatment. During the current pandemic, there is an intense effort to identify new drugs or repurpose FDA-approved drugs to treat COVID-19. Several potential COVID-19 therapeutics are known ototoxins, including chloroquine (CQ) and lopinavir-ritonavir, demonstrating the necessity to identify ototoxic potential in existing and novel medicines. Furthermore, several factors are emerging as potentiators of ototoxicity, such as inflammation (a hallmark of COVID-19), genetic polymorphisms, and ototoxic synergy with co-therapeutics, increasing the necessity to evaluate a drug's potential to induce ototoxicity under varying conditions. Here, we review the potential of COVID-19 therapies to induce ototoxicity and factors that may compound their ototoxic effects. We then discuss two models for rapidly detecting the potential for ototoxicity: mammalian auditory cell lines and the larval zebrafish lateral line. These models offer considerable value for pre-clinical drug development, including development of COVID-19 therapies. Finally, we show the validity of in silico screening for ototoxic potential using a computational model that compares structural similarity of compounds of interest with a database of known ototoxins and non-ototoxins. Preclinical screening at in silico, in vitro, and in vivo levels can provide an earlier indication of the potential for ototoxicity and identify the subset of candidate therapeutics for treating COVID-19 that need to be monitored for ototoxicity as for other widely-used clinical therapeutics, like aminoglycosides and cisplatin.

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“…Identifying medical conditions with a high or potentially deadly impact on the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a critical initial step towards containment of associated morbidity and mortality risks. Given that viral stress from SARS-CoV-2 elicits anabolic responses supported by increasing blood pressure to meet enhanced oxygen needs of vital organs and organ systems, hypoxemia is rendered a high-risk medical condition [1,2]. As the most common blood disorder affecting approximately one third of the global population, anemia presents a low tolerance to hypoxemia and may have either acquired polysystemic or inherited poly-or monogenic background [3].…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of β-Thalassemia Heterozygotes to COVID-19

Sotiriou

Samara

Vamvakopoulou

et al. 2021

JCM

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Background: β-Thalassemia is the most prevalent single gene blood disorder, while the assessment of its susceptibility to coronavirus disease 2019 (COVID-19) warrants it a pressing biomedical priority. Methods: We studied 255 positive COVID-19 participants unvaccinated against severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), consecutively recruited during the last trimester of 2020. Patient characteristics including age, sex, current smoking status, atrial fibrillation, chronic respiratory disease, coronary disease, diabetes, neoplasia, hyperlipidemia, hypertension, and β-thalassemia heterozygosity were assessed for COVID-19 severity, length of hospitalization, intensive care unit (ICU) admission and mortality from COVID-19. Results: We assessed patient characteristics associated with clinical symptoms, ICU admission, and mortality from COVID-19. In multivariate analysis, severe-critical COVID-19 was strongly associated with male sex (p = 0.023), increased age (p < 0.001), and β-thalassemia heterozygosity (p = 0.002, OR = 2.89). Regarding the requirement for ICU care, in multivariate analysis there was a statistically significant association with hypertension (p = 0.001, OR = 5.12), while β-thalassemia heterozygosity had no effect (p = 0.508, OR = 1.33). Mortality was linked to male sex (p = 0.036, OR = 2.09), increased age (p < 0.001) and β-thalassemia heterozygosity (p = 0.010, OR = 2.79) in multivariate analysis. It is worth noting that hyperlipidemia reduced mortality from COVID-19 (p = 0.008, OR = 0.38). No statistically significant association of current smoking status with patient characteristics studied was observed. Conclusions: Our pilot observations indicate enhanced mortality of β-thalassemia heterozygotes from COVID-19.

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Silent hypoxia in COVID-19: pathomechanism and possible management strategy

Cited by 124 publications

References 31 publications

Association between the degree of obstructive sleep apnea and the severity of COVID-19: An explorative retrospective cross-sectional study

Association between the degree of obstructive sleep apnea and the severity of COVID-19: An explorative retrospective cross-sectional study

Detecting Novel Ototoxins and Potentiation of Ototoxicity by Disease Settings

Susceptibility of β-Thalassemia Heterozygotes to COVID-19

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