"Silent" hypoxia: the invisible killer of COVID-19 patients

By Amy Oh

A patient whose only symptom was feeling “cold”; another patient who was casually using their phone; another who came in for a fall injury. All 3 patients who came to the Emergency department had dangerously low levels of oxygen and were diagnosed with Covid pneumonia. But why didn’t they show signs of hypoxia (low oxygen levels)? The oxygen saturation of a healthy person is at least 95%. Typically, people show dyspnea (breathlessness) and lightheadedness before losing consciousness when oxygen saturation decreases to 75%. However, Covid patients- like the patient whose only symptom was feeling “cold”- had oxygen saturations as low as 30% and were fully conscious. Some did not even experience shortness of breath. This is due to “happy” or “silent” hypoxia. 

The “silent” nature of hypoxia associated with the covid pneumonia makes it harder to detect. Patients with pneumonia - an infection where alveoli fill with fluids- usually show symptoms such as chest discomfort, pain and shortness of breath. However, those with covid pneumonia do not show such symptoms at first, and by the time they do, they have moderate to severe pneumonia, extremely low levels of oxygen, and extensive lung damage. 

Coronavirus attacks the surfactant-producing cells, which causes alveoli to collapse and oxygen levels to fall. Initially, the lung is not filled with fluid which means the patient can still exhale carbon dioxide, hence they do not feel out of breath. The patients then try to increase the oxygen levels by breathing deeper and faster, which causes further inflammation and more alveoli collapsing. This may be why 20% of COVID-19 patients develop a second phase of lung injury. 

Therefore, some doctors suggest that people use a “pulse oximeter” to monitor their own oxygen saturation levels when they first develop coronavirus symptoms, such as a fever or loss of smell. This way, people can go to the hospital for treatment before their covid pneumonia progresses. There are some indications that early treatment is linked to better recovery: most Korean patients diagnosed with COVID-19 are monitored in hospitals when they show symptoms, which may be one of the reasons why the death rate is so low in Korea compared to other countries. Early treatment means less people will have to be on ventilators, which would massively ease the burden on the healthcare system. 

There is also a hypothesis on the physiology behind “happy” hypoxia. COVID-19 patients, as mentioned before, have very low levels of oxygen, but have close to normal levels of CO2. This means the brain blood flow is maintained, as cerebral arteries vasoconstrict when CO2 levels decrease. In the brain, low levels of oxygen also mean there is less aerobic respiration, so less CO2 is produced. These two factors combined, CO2 is rapidly removed from brain tissue, which results in low levels of CO2 in the brain. Central chemoreceptors located in the brain are activated by increased CO2 levels. These chemoreceptors are responsible for triggering a sense of breathlessness and distress. Therefore, it is plausible that COVID-19 patients have inactivated central chemoreceptors, and so do not feel out of breath. 

An additional hypothesis is that the peripheral (different to the central) chemoreceptors are hijacked by the SARS-CoV-2, and therefore become dysfunctional. Peripheral chemoreceptors are activated in hypoxia, and stimulate breathing. However, the virus may decrease the response of HIF (hypoxia inducible factor), which is crucial for oxygen sensing in the carotid body. Furthermore, the virus is neurotoxic (damaging to the brain and nervous system), as shown by the common early symptom of loss of smell and taste. To explain, “taste” is mediated by sensory nerves between tongue and brain, which are located in the same ganglion (structure containing a number of nerve cell bodies) that relays carotid body signals to the brain. So if these are damaged, the brain cannot detect the low oxygen levels. 

There are many developing theories about reasons behind “happy” hypoxia in COVID-19 patients, but its effects have definitely taken doctors and scientists by surprise. Due to the unfamiliar nature of the coronavirus, there is so much to be researched and uncovered to further our understanding and optimise the treatments for the patients.