Physiological loads	COVID-induced physiological changes	Ventilatory drive modulation
Hypoxemia	In early infection, arterial hypoxemia is primarily caused by V/Q mismatches and increases in P(A-a)O₂ gradients. As a result of local interstitial edema, acute inflammation, endothelial injury, and intrapulmonary shunting, oxygen diffusion is decreased [20] .	In mild hypoxemia (PaO₂ between 60 - 70 mmHg), the respiratory drive is typically unaffected, often presenting as “happy hypoxemia” without dyspnea. Due to hypoxemia worsening as PaO₂ decreases, respiratory drive increases gradually.
Hypercapnia and acidosis	Peripheral chemoreceptors sense changes in arterial blood directly, while central chemoreceptors sense changes in chronic hypercapnia through the pH of CSF [1] .	Respiratory rate and arterial pCO₂ have inverse associations [81] .
Intrapulmonary shunting and V/Q mismatching	Dead space can be caused by thrombosis in hypercoagulable states (an elevated level of D-dimer, fibrinogen, or interleukin-6 markers) [82] .	The ratio of dead space to tidal volume (V_D/V_T) may cause endothelial injury and microvascular coagulation [30] [83] .
Decreased respiratory compliance	An index of rapid shallow breathing (Respiratory rate divided by tidal volume). Ventilatory demand may not be met by excessive drive [84] .	When drive increases, respiratory rate increases, resulting in a decrease in respiratory time.
Anemia	An infection with this virus can result in a greater production of immature RBCs, followed by their release into the bloodstream and a consequent drop in Hb levels [85] .	A greater respiratory drive is induced when hypoxemia occurs due to chemoreceptor sensitivity to PaCO₂.
Impairment in respiratory muscle strength (muscle fatigue)	The reduction of forced vital capacity (FVC) and lung diffusing capacity in survivors of COVID-19 [5] .	Resulting in a reduced tidal volume and an increased work of breathing due to neuromechanical dissociation.
Pulmonary vasoconstriction	Hypertension is etiologically linked to RAAS dysfunction. The cellular receptor for COVID-19 is ACE2. ACE converts angiotensin I into Ang II and degrades bradykinin. When ACE2 levels are low, RAAS is activated, resulting in pulmonary vasoconstriction [86] .	ACE2 plays a role in neuroinvasion, as it is expressed in the brain on neurons and glial cells, particularly in the brainstem, in the paraventricular nucleus, and in the rostral ventrolateral medulla [7] . The drive may be blunted.
Decreased diffusion capacity and rise in P(A–a) O₂ gradient	An infection results in moderate interstitial edema and surfactant loss. Alveolar collapse results in intrapulmonary shunting, resulting in non-aerated alveoli being perfused [32] [87] .	Carotid body chemoreceptors are stimulated by low PO₂ resulting in increased drive
Shift in oxygen dissociation curve or increased P₅₀ values	An oxygen dissociation curve shift caused by fever may result in lower arterial oxygen saturation levels.	Silent hypoxemia is believed to occur due to this phenomenon, combined with the carotid bodies’ response to decreased PaO₂ rather than SaO₂ [18] .
Autonomic dysfunction	The neuro-vagal anti-inflammatory reflex may be impaired by hypoxemia-induced reductions in parasympathetic activity and sympatho-excitation. There is a possibility that this impairment could contribute to the emergence of a cytokine storm [4] .	Tachypnea may be caused by pro-inflammatory cytokines in the brainstem [57] .