Studies to Determine Whether Oxygen Sensing is Impaired in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infected Patients

Many patients infected with SARS-CoV-2 are hypoxic (O2 blood saturation below 92%). Many do not even realize they are hypoxic, since breathing can remain comfortable. In these patients, the normal physiologic responses to low oxygen, increased respiration, appears to be absent (Couzin-Frankel, 2020).

A wide variety of cell types within the body express the ACE2 receptor that is required by the virus to infect cells. This included the cells of the carotid body, which are the O2 sensors of the body. The investigators hypothesize that glomus cells of the carotid body are among the first cells infected due to their extremely high blood perfusion rates. After infection, they are "offline" and the body no longer recognizes that it is hypoxic. This can be extremely detrimental to patients that may require mechanical ventilation to re-establish normal blood O2 levels (>95% saturation). Death rates on patients using mechanical ventilators are very high and every effort should be made to keep patients off these machines.

Interestingly, hypoxia appears to be a common condition in SARS-CoV-2 infected people, with some showing serious respiratory conditions (acute respiratory distress syndrome - ARDS), but others not. The majority appear to die from a "cytokine storm", a massive reaction to the infection by the immune system (Xie et al., 2020). But many others are hypoxic and sick. Many medical centers are treating SARS-Cov-2 patients identically, placing them on mechanical respirators. Below is a short description from a German group from an editorial that was recently published (Gattinoni et al., 2020) suggesting that not all SARS-CoV-2 hypoxic patients are the same and so should not be treated identically.

It has been known for a long time that mechanical ventilation in ICU patients, not related to SARS-CoV-2, can be very hard on patients with death rates above 50% (Fialkow et al., 2014) and with very long recovery times (Griffiths & Jones, 1999). Patients admitted to ICUs who need mechanical ventilation are expected to have higher mortality rates compared with those who do not require respiratory support (Vincent et al., 2002) as a consequence of ventilator-induced lung injury (VILI). Intubated patients infected with SARS-CoV-2 also have very high death rates (Richardson et al., 2020). Undoubtedly, they are the sickest of the sick. Nonetheless, everything possible should be done to prevent intubation a policy consistent with University of Chicago usage of high flow nasal cannulation. The investigators goal with this IRB submission is to identify a cohort of SARS-CoV-2 patients that are hypoxic but their breathing is not responding correctly to the hypoxia ("silent hypoxia"). It is possible that these patients can be treated with drugs, in order to keep them from intubation for as long as possible.

Phase I - Study of silent hypoxia in SARS-CoV-2 infected patients. Phase 1 will recruit 40 subjects with documented SARS-CoV-2 infection and another 40 healthy subjects as the control group. Totaling 80 subjects in the first phase. This large a group is not required to determine if "silent hypoxia" exists, rather to determine the percentage of patients exhibiting altered oxygen sensing, among this patient population.