Discussion
Patients who presented to our hospital with COVID-19 related respiratory
distress have had varying forms of oxygen supplementation ranging from
those with mild distress on nasal cannulas to those with severe acute
respiratory distress syndrome (ARDS) on invasive mechanical ventilation.
The only variation in the treatment of this patient as opposed to others
was oxygen. The patient in this case was never once supplemented with
any oxygen for the entire duration of admission. The reason for
withholding supplemental oxygen was the relative clinical stability of
this patient despite presenting with hypoxemia. Prior to this case, we
had observed several patients with similar clinical presentation who
were supplemented with oxygen to meet a required high-set oxygen target.
Eventually they ended up having prolonged hospital stay with an
increased oxygen demand overtime. Long-term exposure to high levels of
oxygen can cause lung injury in the absence of mechanical ventilation,
but the combination of these two becomes more lethal leading to further
lung damage.(5)
During viral respiratory illnesses, ROS are necessary for eradicating
viruses, thus aiding immune cells in phagocytoses function and in signal
transduction. Excessive oxygenation can cause the amount of ROS to
exceed the required redox homeostasis leading to histologically
progressive destruction of alveolocapillary membranes causing
obstruction of capillaries forming microthrombi and air leaks via
already injured alveoli into the surrounding tissues.(6) Eventually
prolonged iatrogenic exposure to oxygen in combination with COVID-19 can
exacerbate cell apoptosis at the alveolar epithelium level resulting
into pulmonary fibrosis over an extended time period.(7)
Lung tissues are protected by overactive immune mediated Adenosine
A2A receptor cells. These immune cells play a critical
role in the down-regulation of pulmonary inflammation. Uncontrolled
pulmonary inflammation occurs when continuous amount of oxygen is
administered that weakens the Adenosine A2A receptor
mediated anti-inflammatory mechanism, thereby further exacerbating lung
damage.(8) A study done on a small population receiving inhaled
Adenosine showed promising results in patients with COVID-19 in an
attempt to therapeutically compensate for the oxygen-related loss of the
endogenous adenosine receptor (A2AR)-mediated cells and
reduce the lung destructing inflammatory process.(9)
Most pulmonary and non-pulmonary related studies recommend that no
oxygen supplementation is required when oxygen saturation is more than
92%. Oxygen supplementation should start only if oxygen saturation is
less than 90%.(10) However no consensus has yet been established on
what the oxygenation target should be in hypoxemic respiratory failure
patients.(11)
A meta-analysis study published even before the COVID-19 pandemic
described that hyperoxia for a duration of more than 12 to 24 hours
often led to serious deleterious side-effects. It was also noted that
hyperoxia of even shorter durations may be associated with increased
morbidity and mortality in ICU patients.(12) The mortality rates of
acutely ill adults in multiple clinical syndromes were lower in those
who received conservative amount of oxygen as opposed to the liberal
batch.(13)
Recent observation proposes no direct evidence of the benefit of
providing supplemental oxygen therapy in the absence of hypoxia in
COVID-19 patients such as in patients with low oxygen saturations who
are perfectly comfortable or rather, “happy hypoxemic.” It may be used
to wean patients off ventilatory support but its use on patients whose
lungs have adapted to hypoxemia or who do not require invasive therapy
may in turn lead to adverse consequences.(2) Overcorrecting hypoxemia
may improve it in the short term, but its long term effects can lead to
oxygen induced ARDS and ventilator associated lung injury. This data
suggests that the lungs have a better chance of recovery from COVID-19
when exposed to less oxygenation and invasive ventilation. Permissive
hypoxemia was found to be feasible and had a better patient outcome when
focused on oxygen content (CaO2) rather than oxygen
saturations (SaO2).(14)
Based on these oxygen studies and our observation of patients, we could
postulate that in patients undergoing a cytokine storm due to COVID-19,
prolonged and excessive oxygen therapy adds insult in the form of oxygen
reactive species, to an already injured lung. We do not know if this is
an isolated case among millions or whether depriving this patient of
oxygen did indeed work to his benefit. COVID-19 pneumonia no doubt
requires some form of oxygen, but the conundrum lies with those
presenting with a mild form of respiratory distress, who despite having
low saturations have minimal to no discomfort. COVID-19 respiratory
distress presents with an unconventional pathogenesis in terms of
hypoxemic patients and their progression to ARDS. Oxygen can do both,
heal and harm, and in the setting of COVID-19, which is still a new
evolving disease, the question isn’t really about whether or not oxygen
is required, but rather how much is required.