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Silent Hypoxia in COVID-19 Patients

Hypoxia is a dangerous symptom of SARS-CoV-2. This occurs when the body’s tissues do not receive enough oxygen, leading to irreparable damage if gone undetected for too long. In normal conditions, a person’s blood oxygen saturation level should be around 94-100%. Anything lower than this will result in organ damage and possibly death.


Image is courtesy of Shutterstock.


What is silent hypoxia?


Hypoxia is typically indicated by distress or shortness of breath. However, COVID-19 patients do not display any breathing difficulties despite depleted oxygen levels. This is why the phenomenon is known as "silent"— the symptom is not apparent until it becomes deadly. Most patients will experience fever, cough, and fatigue for a week before experiencing shortness of breath. By the time patients arrive at the hospital, they have alarming oxygen levels and are in critical condition.


An emergency doctor, Dr. Levitan in New York City, writes about his experience, "A vast majority of Covid pneumonia patients I met had remarkably low oxygen saturations at triage — seemingly incompatible with life — but they were using their cellphones as we put them on monitors. Although breathing fast, they had relatively minimal apparent distress, despite dangerously low oxygen levels and terrible pneumonia on chest X-rays."


What causes silent hypoxia?


Silent hypoxia has become a mystery to physicians, as its exact cause is unknown. It is speculated that SARS-CoV-2 causes the air sacs in the lungs to collapse, reducing oxygen levels but still maintaining the lung's normal ability to expel carbon dioxide. The removal of carbon dioxide could explain why COVID-19 patients do not feel shortness of breath.


Several other hypotheses have been made on the case of silent hypoxia:


In November of 2020, scientists at Boston University used computer modelling to conduct a study. They discovered silent hypoxia is caused by a combination of simultaneous biological mechanisms in the lungs. Preliminary clinical data suggested that patients' lungs had lost the ability to restrict blood flow to already damaged tissue. The lungs were speculated to open blood vessels even more, supplying a higher than normal blood flow to the lung areas that can no longer gather oxygen. The scientists also studied how blood clotting impacted blood flow. SARS-CoV-2 was found to cause tiny blood clots from inflammation, which could incite silent hypoxia. Lastly, they looked at whether COVID-19 affects the normal ratio or air-to-blood flow for normal lung function. Their findings suggested that the mismatch of ratio may be happening in parts of the lung that do not appear abnormal, leading to silent hypoxia.


Another hypothesis includes dysfunction of the brainstem respiratory center and pulmonary C-fibers. The respiratory center is located in the medulla oblongata and pons. Its main function is to send signals to muscles that control respiration and breathing. Evidence shows that SARS-CoV-2 can infect neurons, possibly due to entry from the olfactory nerve (which has relation to the nose). SARS-CoV-2 affects the pre-Botzinger nucleus in the brain, which acts as a centre for respiratory control.


Diagram of brainstem and respiratory centre location (Pearson).


Alternatively, SARS-CoV-2 also has the ability to destroy pulmonary C-fibers. These are afferent neurons, which carry stimulus to the brainstem. They are located in the lung capillaries and are responsive to events such as pneumonia and congestive heart failure, causing an increase in respiration when oxygen levels are low. The destruction of these neurons could explain why patients do not report shortness of breath even when oxygen levels dip below normal.


Lastly, the decline of oxygen tension is also detected by cells in the carotid body. The carotid body is a small mass of receptors in the carotid artery near the neck. In a study published on Oxford Academic, researchers hypothesized that the carotid body contained high levels of ACE2, also known as angiotensin-converting enzyme 2. ACE2 is a protein on the surface of many cell types that SARS-CoV-2 binds to. The findings proved that the carotid body contained high levels of ACE2 but was variable among cases, with no correlation between gender or donor age. This could explain why silent hypoxia is also variable between patients.


SARS-CoV-2 binding to ACE2 receptor (The Conversation).


Prevention


Early detection of silent hypoxia prevents patients from being treated with highly invasive intubation and ventilation procedures. Machine shortage and resource scarcity are one of the biggest reasons why health systems are struggling. Ultimately, preventing critical lung care will reduce admissions and the mortality rate of COVID-19.


One way to detect lowering oxygen levels includes using a pulse oximeter. These can be purchased at pharmacies and retail stores. The device measures oxygen saturation and pulse rate. However, this should not be used as the first step in COVID-19 screening. Other symptoms like fever and cough should be considered first.


A pulse oximeter (Getty Images).


New technology has also provided smartphones that can act as pulse oximeters. Using a Samsung Galaxy S8 smartphone, relatively accurate readings can be achieved, compared to medical-grade devices.


References


Garg, Ravindra K, et al. “Silent Hypoxemia in COVID-19: Dangerous, If Gone Undetected.” Neurology India, 27 Oct. 2020, https://neurologyindia.com/article.asp?issn=0028-3886;year=2020;volume=68;issue=5;spage=1261;epage=1262;aulast=Garg;type=3

Online, ET. “Decoding Silent Hypoxia in Covid Patients: Blue Lips, Changing Skin Colour, Sweating for No Reason.” The Economic Times, Economic Times, 29 Dec. 2020, https://economictimes.indiatimes.com/magazines/panache/decoding-silent-hypoxia-in-covid-patients-blue-lips-changing-skin-colour-sweating-for-no-reason/articleshow/80009671.cms

Teo, Jason. “Early Detection of Silent Hypoxia in Covid-19 Pneumonia Using Smartphone Pulse Oximetry.” Journal of Medical Systems, Springer US, 19 June 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305055/

“Three Reasons Why COVID-19 Can Cause Silent Hypoxia.” ScienceDaily, ScienceDaily, 19 Nov. 2020, https://www.sciencedaily.com/releases/2020/11/201119153946.htm

Villadiego, Javier, et al. “Is Carotid Body Infection Responsible for Silent Hypoxemia in COVID-19 Patients?” OUP Academic, Oxford University Press, 23 Nov. 2020, https://academic.oup.com/function/article/2/1/zqaa032/5998649



Article Author: Jennifer Law

Article Editors: Victoria Huang, Maria Giroux

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