Syndrome of inappropriate antidiuretic hormone secretion associated with a SARS-CoV-2 pneumonia

Dear Editor,

A fifty-two year old man, without toxic habits and on treatment with an angiotensin-converting enzyme inhibitor for arterial hypertension and with no other previous diseases presented to the emergency room with cough and fever of 39 °C of ten days duration, and dyspnoea, reduced general condition and diarrhoea in the last 48 h. He did not refer contact with any subject testing positive for SARS-CoV-2 and he had been confined to his home for the last three weeks. Respiratory examination of the patient revealed bilateral basal crackles, with no other manifestations on the physical exam, including no dehydration signs or limbs oedema. In the emergency room, the patient normal blood pressure (SBP 149 mmHg–DBP 80 mmHg), fever (38.3 °C) and resting oxygen saturation of 92%. Peripheral bilateral infiltrates suggesting COVID-19 bilateral pneumonia were observed on x-ray examination. SARS-CoV-2 infection was confirmed by nasopharyngeal swabs. He was admitted to hospital. The first blood analysis showed: Na, 127 mmol/l; K, 3.7 mmol/l; glucose, 122.5 mg/dl; urea, 22.8 mg/dl, calculated plasma osmolarity 268 mOsm/kg. Hyponatremia persisted for 48 h after admission with plasma Na 128 mmol/l and urine Na 77 mmol/L; urine K 65 mmol/l; urine osmolarity 1228 mmol/kg. The rest of blood analysis showed abnormal parameters reflecting COVID-19 infection, such as: lymphocyte count 680 × 10e9/L, D-Dimer 880 ng/ml; lactate dehydrogenase 377 U/L; creatine kinase 824 U/L; C-reactive protein 47.9 mg/L. Room air arterial blood gases showed pH 7.48, pCO₂ 31 mmHg, pO₂ 63 mmHg and oxygen saturation of 92%. Thyroid hormone and basal cortisol levels were within the normal range. Empirical treatment for SARS-CoV-2 bilateral pneumonia was started following the local guidelines with hydroxychloroquine, azithromycin, ceftriaxone and lopinavir/ritonavir. The patient drank 1500 ml of water per day approximately and he did not take any hyponatremia-inducing drugs. SIADH was suspected on the basis of blood and urine tests and physical exam findings, and hypertonic saline and fluid restriction were prescribed, with normalization of serum sodium at day six of hospital admission. Clinical and radiological bilateral COVID-19 pneumonia improved and the patient was discharged after six days of admission.

SIADH is a common cause of hyponatremia in patients admitted to hospital. The median age of SIADH-associated aetiology is 70 years (range: 38–88). It is associated to higher mortality and morbidity and with a delay in hospital discharge. SIADH diagnostic criteria include serum Na < 135 mmol/l, serum osmolarity < 275 mOsm/kg, inadequate urine concentration > 100 mOsm/kg, the absence of hypo- or hypervolemia signs, urine Na > 40 meq/l with a salt and a normal fluid intake. Hypothyroidism, suprarenal insufficiency, renal failure or diuretic intake must be discarded.

The most frequent causes of SIADH include malignancies, lung diseases, different kinds of drugs and central nervous system disorders.

In 2003, hyponatremia associated to SARS infection was reported in 60% of patients.¹ Even though no specific data are available on the association of hyponatremia in SARS-CoV-2 infection, a recent study has described a 50% prevalence, although reporting a small number of patients.²

Previous studies have related SIADH to lung diseases reaching prevalence between 10 and 45% in patients affected by microcytic pulmonary carcinoma.³ Influenza type A virus infections have been related to SIADH in a few number of cases. In paediatrics, SIADH was detected in 18% of children under 12 month who were admitted for respiratory syncytial virus bronchiolitis, observing a higher incidence of pneumonia and intensive care requirements.⁴ The incidence of hyponatremia in patients admitted for community-acquired pneumonia was 8.3%, with a 46% of them caused by SIADH.⁵

We report this case to point to the importance of detecting the aetiology of hyponatremia due to treatment considerations. Current guidelines usually recommend caution with extra fluid therapy in patients with serious COVID-19 due to risk of respiratory distress. The finding that hyponatremia may be present in up to 50% of patients with COVID-19 admitted to hospital highlights the importance of a differential diagnosis including SIADH in this group of patients.

Conflict of interest

None.