**3. COVID-19 and SIADH-induced hyponatremia**

The exact mechanism of hyponatremia following COVID-19 infection has yet to be well established. However, the animal models speculated that it could be due to an imbalance in the intravascular fluid volume and extracellular fluid osmolality. Low volume intravascularly would activate the osmoreceptor and increase the ADH secretion [15].

Stresses, whether physical or non-physical, caused by infection for an instance, as in COVID-19, trigger the hypothalamus-pituitary axis, which leads to ADH secretion. In addition, lung involvement due to COVID-19 resulted in ventilation-perfusion mismatch leading to hypoxic pulmonary vasoconstriction, eventually filling the left atrium. The inability of the left atrium to stretch appropriately and as a consequent of this filling, the ADH will be released, **Figure 2** [18].

Several studies have reported that the association of pneumonia with SIADH; however, few case reports have discussed SIADH secondary to COVID-19 pneumonia [19, 20].

One of observed initial COVID-19 clinical manifestation was SIADH. The potential mechanism was attributed to sepsis and cytokine storm associated with it (excessive IL-6 release), which in turn leads to hypothalamic–pituitary axis activation and subsequent uncontrolled release of anti-diuretic hormone (ADH) [15, 16].

Rizki et al. recently had published a systematic review and meta-analysis to assess the prognostic value of hyponatremia in COVID-19 patients. They found that SIADHinduced hyponatremia was associated with longer intensive care unit (ICU) stay and high mortality rate [21]. This could be explained by water retention induced by high levels of the ADH. Intravascular fluid retention can lead to extravasation due to increased capillary permeability in patients with COVID-19 sepsis which may subsequently increase the requirements of ventilator settings and ICU stay [15, 16, 21–23].

Critical levels of hyponatremia can lead to serious neurological manifestations including seizures, loss of consciousness and even death due to cerebral edema and brain stem compression. On the other hand, rapid correction of hyponatremia can lead to devastating neurological insult such as the osmotic demyelination syndrome [7, 24]. Therefore, proper management of covid-19 infection may result in decreased cytokine storms and eventually decreased ADH secretion [25, 26]. The decision of fluid administration in patients with sepsis as an attempt to improve the hydration and circulation status needs to be taken very carefully. Desalination is a phenomenon in which administration of normal saline in patients with SIADH-induced hyponatremia leads to worsening of hyponatremia. The hypothesized mechanism of this phenomenon is related to the excretion of some of the administered fluids in

#### **Figure 2.**

*Hemodynamic changes in early COVID-19 infection [18].*

the hyperosmolar urine leaving the remaining in the circulation which leads to more hypotonic plasma and therefore worsening of pre-existing hyponatremia [24, 27]. Thus, the primary target in treating those patients is to the primary disease i.e. the COVID-19 infection. This will consequently lead to improvement of SIADH-induced hyponatremia and improved patients' outcomes.

## **4. Conclusion**

COVID-19 is associated with the development of SIADH; therefore, this condition should be considered in the differential diagnosis in patients with hyponatremia. Administration of IVF warrants cautious decision-making in these settings to avoid worsening of hyponatremia.

*Coronavirus 19 (COVID-19) and Syndrome of Inappropriate Anti-Diuretic Hormone Secretion… DOI: http://dx.doi.org/10.5772/intechopen.110717*
