COVID-19 presenting with diarrhoea and hyponatraemia.

COVID-19 is a viral disease with a high infectivity rate. The full spectrum of the disease is not yet understood. This understanding may help in limiting potential exposure. We present a young man with diarrhoea, abdominal pain and hyponatraemia who turned out to be positive for COVID-19. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Background

COVID-19 is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Fever is a common presenting symptom, along with cough, dyspnoea, myalgia and fatigue. Severe cases may lead to organ dysfunction and death.1

As with any infectious disease, one of the challenges with COVID-19 is to understand both the typical and atypical disease presentations. Atypical presentations carry the risk of going undetected for a longer duration, and in turn may lead to the spillover of the disease in a healthcare setting as well as the community.

Case presentation

A 27-year-old Indian man, with known type 2 diabetes, presented with a 5-day history of gradually progressive, moderate severity, generalised abdominal pain. The pain was accompanied by watery diarrhoea five to six times per day. He did not have any fever, sore throat, myalgias, influenza-like symptoms or shortness of breath. A review of systems was remarkable for dry cough of similar duration.

There was no recent history of travel and no sick contacts or animal exposure.

On initial presentation, he was not febrile, tachypnoeic, tachycardiac or hypotensive. Physical examination revealed a patient in distress due to abdominal pain. There was mild generalised abdominal tenderness, but no guarding, rigidity or rebound. The chest examination showed coarse bibasal crackles. The rest of the physical examination was unremarkable.

Initial work-up revealed normocytic anaemia, thrombocytopaenia and non-elevated inflammatory markers. Two repeated samples confirmed asymptomatic hyponatraemia. Liver enzymes, renal function and the endocrine panel were unremarkable. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) was the probable cause of hyponatraemia (table 1).

Table 1

Laboratory work-up on admission

White cell count	4.6×109/L
Red blood cells	4×1012/L
Haemoglobin	110 /L
Mean cell volume	85.6 fL
Mean cell haemoglobin	27.8 pg
Platelets	110×103/μL
Glucose	14.4 mmol/L
Sodium corrected for glucose	120 mmol/L
Osmolality, serum	298 mmol/kg
Osmolality, urine	789 mmol/K
Sodium, urine	73 mmol/L
Procalcitonin	0.5 μg/L
C reactive protein	118 mg/L

On the first day of admission, the patient developed high-grade fever. He was placed under isolation and screened for viral respiratory infections. The patient turned out to be positive for COVID-19.

Differential diagnosis

Given the patient’s chief complaint of abdominal pain with diarrhoea, gastroenteritis was the initial working diagnosis. There was no food intake from outside and no sick contacts. Stool analysis for ova and parasites was negative. Also, ELISA immunoassay for Clostridium difficile toxin came out negative. Stool culture was unrevealing. Stool PCR for SARS-CoV-2 was unavailable in the local hospital lab.

Pancreatitis was another differential, but lipase was negative. Atypical pneumonia was another possibility considering the minimal respiratory symptoms and bilateral chest X-ray findings (figure 1). The patient did not produce any sputum for culture, and two sets of blood cultures were negative. Due to hyponatraemia, Legionella pneumonia was considered; however, the urinary antigen was negative.

Figure 1

Chest X-ray showing bilateral infiltrates, more on the bases. PA, posteroanterior.

Viral pneumonia was another diagnostic possibility for which a viral panel was sent, which included SARS-CoV-2 PCR, which eventually came back positive and hence confirmed the diagnosis of the novel coronavirus pneumonia (table 2).

Table 2

Work-up for infective aetiology assessment

Blood cultures (2 sets)	Negative
Stool culture	Negative
Stool for ova/parasite	Negative
Stool for Clostridium difficile (ELISA Ab)	Negative
Respiratory syncytial virus	Negative
Parainfluenza	Negative
Influenza virus A PCR	Negative
Influenza virus B PCR	Negative
Rhinovirus PCR	Negative
COVID-19 PCR	Positive
Legionella Ag	Negative

Ab, antibody; Ag, antigen.

Treatment

The patient was initially started on ceftriaxone, azithromycin and oseltamivir as empirical therapy for community-acquired pneumonia. After the tests for COVID-19 PCR from nasal swab came positive, the patient received chloroquine phosphate 250 mg two times per day, darunavir/cobicistat 950 mg daily and ribavirin 1200 mg two times per day for 14 days, based on local guidelines. Ribavirin 1200 mg two times per day was added to his antiviral regimen. The patient remained clinically stable throughout the hospital course until discharge.

Outcome and follow-up

The patient’s abdominal pain and diarrhoea resolved without any specific management. He did not require any ventilatory support during his stay. His SARS-CoV-2 PCR turned negative on repeat testing after 2 weeks and he was discharged home.

Discussion

The novel coronavirus belongs to a group of severe acute respiratory syndrome-related coronaviruses.2 It originated in Wuhan, Hubei Province, China, in December 2019 and was declared a pandemic by WHO on 11 March 2020.3

The most common clinical features are fever, dry cough, myalgia, anorexia and dyspnoea.4 Gastrointestinal symptoms such as diarrhoea, abdominal pain and vomiting have been previously seen with acute viral respiratory infections and reported recently as rare manifestations of COVID-19.4–6 The confirmation of a suspected case relies on SARS-CoV-2 RNA detection via PCR.

Watery diarrhoea is present in SARS-CoV-1 infection secondary to virus replication within the intestinal cells.7

The presence of gastrointestinal symptoms in coronavirus infection (SARS-CoV-1 and SARS-CoV-2) can be linked to the distribution of ACE2 receptor, which is present in lung alveolar type 2 cells, as well as in enterocytes.8

Acute hyponatraemia is present in atypical pneumonia, especially Legionella.9 The underlying mechanism is the syndrome of inappropriate antidiuretic hormone (ADH) secretion.10

There is a rapidly accumulating body of knowledge regarding the epidemiology, pathophysiology, clinical manifestations, infection control and management of COVID-19. Like any other RNA virus, SARS-CoV-2 attacks the host cell, and penetrates and enters the nucleus for replication. The virus has an affinity to ACE2 as binding receptors.11 This affinity is the probable reason that the lungs are the most commonly affected organs.

The response of the host organ can be from minimal symptoms to organ failure. T cell immune response to the coronaviruses has been studied in the past.12 Another common disease phenomenon observed and reported is a hypercoagulable state, which can be explained by the expression of ACE2 enzymes by the endothelium.13 Similarly, the gastrointestinal tract also expresses ACE2, leading to a viral attack of the system.14

There is ongoing research to understand the pathophysiology of COVID-19 infection.

An important aspect is to understand the atypical presentation of the disease. Timely detection of suspected cases with prompt isolation and screening is one of the factors that may help curb the spread in the community.15 Our patient had acute hyponatraemia, abdominal pain and diarrhoea with minimal respiratory symptoms, which he did not self-report. The cough history was elicited during a thorough review of the system. This atypical presentation led to inadvertent exposure to healthcare personnel. Therefore, during the pandemic, a similar presentation should be considered for COVID-19.

I am having a difficult time because of this pain in my stomach. Nothing has changed in my diet, and I have been following my same daily routine, but I do not understand why I have this pain and diarrhea. I hope it is some kind of a minor infection and goes as speedily as it came. (The perspective is from the initial encounter.)

Knowing the atypical presentation of the disease is as important as knowing a typical presentation.

Anyone with gastrointestinal symptoms with no alternative explanation should be isolated and screened for COVID-19.

Early screening may impact the spread of the disease.

We recommend studies to evaluate the effectiveness of stool PCR for severe acute respiratory syndrome coronavirus 2 if initial nasopharyngeal PCR is negative and suspicion remains high.