Hantavirus Pulmonary Syndrome (HPS) is caused by North and South American hantavirus strains and kills roughly one in three people who contract it, even in modern ICU settings. What makes it particularly dangerous is the speed at which it progresses from apparent mild illness to life-threatening respiratory and cardiac failure — often within 24–48 hours.
Understanding the clinical course is essential for patients, caregivers, and clinicians in endemic regions.
What Causes HPS?
HPS is caused by inhalation of aerosols contaminated with excreta from infected rodents. In North America, Sin Nombre virus (SNV) — carried by the deer mouse (Peromyscus maniculatus) — is the primary cause. In South America, Andes virus (ANDV) — carried by the long-tailed pygmy rice rat (Oligoryzomys longicaudatus) — causes the most cases, with a slightly higher case fatality rate than Sin Nombre.
Once inhaled, the virus infects endothelial cells — the cells lining blood vessels — throughout the body. This causes a severe increase in vascular permeability, particularly in the lungs: capillaries begin to leak fluid into the lung tissue and air spaces, causing the non-cardiogenic pulmonary oedema that is the hallmark of HPS.
The Four Clinical Phases
1. Incubation Phase (1–8 weeks, most commonly 2–4 weeks)
During this period the patient has no symptoms but the virus is replicating silently. The wide range reflects variation between individual immune responses and viral inoculation dose. This is clinically invisible — there are no tests that reliably detect early HPS infection before symptoms begin.
2. Prodromal Phase (3–5 days)
The prodromal phase is the most deceptive stage of HPS because it is clinically indistinguishable from influenza or any other febrile illness. Typical symptoms include:
- Fever (usually 38–40°C)
- Myalgia — severe muscle aches, often in the back, thighs, and hips
- Headache — often severe
- Fatigue and malaise
- Nausea, vomiting, abdominal pain (more prominent in Andes virus cases than Sin Nombre)
- No cough, runny nose, or sore throat — the absence of upper respiratory symptoms is an important negative finding that should raise clinical suspicion in patients with rodent exposure history
This phase is the critical diagnostic window. Patients who can tell a clinician “I was cleaning a rodent-infested cabin three weeks ago” during the prodromal phase can potentially receive monitoring and early supportive care before the life-threatening phase begins.
3. Cardiopulmonary Phase (hours to days)
The transition from prodromal to cardiopulmonary phase can occur suddenly, sometimes within hours. This is the defining and most dangerous phase of HPS. Features include:
- Cough with progressive dyspnoea — often the first sign that the patient is entering this phase
- Hypoxaemia — oxygen saturation drops rapidly, requiring supplemental oxygen
- Non-cardiogenic pulmonary oedema — the lungs fill with fluid despite normal or low cardiac filling pressures. Chest X-ray typically shows bilateral interstitial infiltrates.
- Haemodynamic instability — blood pressure drops as the heart is directly affected (myocardial depression from the viral process)
- Sinus bradycardia followed by heart block and arrhythmias in severe cases
The severity of this phase correlates with haematological markers that can be seen on standard blood tests:
- Elevated haematocrit (haemoconcentration as fluid leaks from vessels)
- Thrombocytopenia (low platelet count) — a key early warning sign
- Left shift on white cell differential — immature neutrophils (myelocytes, metamyelocytes)
- Large immunoblasts on peripheral blood smear — another characteristic finding
- Elevated serum lactate — indicating poor tissue perfusion
These findings on a blood test in a patient with rodent exposure history constitute a medical emergency.
4. Diuretic Phase (if survival)
Patients who survive the cardiopulmonary phase typically enter a diuretic phase over several days, during which the lung oedema begins to resolve, oxygen requirements decrease, and haemodynamic stability returns. Recovery can be surprisingly complete in survivors, though some patients experience prolonged fatigue and reduced exercise tolerance for months.
Diagnosis
Definitive HPS diagnosis requires laboratory confirmation, most commonly:
- IgM ELISA: Detects hantavirus-specific IgM antibodies. Usually positive by the onset of symptoms and is the most practical first-line test. Available through reference laboratories, not routine hospital labs in most countries.
- RT-PCR on whole blood: Can detect viral RNA in the prodromal and early cardiopulmonary phase; sensitivity decreases as symptoms progress and immune response develops.
- IgG ELISA: Detects past infection; useful for confirming convalescent cases but not for acute diagnosis.
Critically, you must tell your clinician about potential rodent exposure for hantavirus to be considered in the differential diagnosis. It is not part of a standard respiratory illness workup. In endemic regions, clinicians should include it; in non-endemic regions, the history is essential.
Treatment
There is no approved antiviral therapy for HPS. Management is entirely supportive and requires ICU-level care:
Fluid management: Extremely challenging. Patients are hypovolaemic (low effective circulating volume) but the pulmonary oedema means that aggressive fluid replacement worsens respiratory failure. Careful, minimal fluid resuscitation is the goal.
Oxygen and ventilatory support: Supplemental oxygen, then high-flow nasal cannula or non-invasive positive pressure ventilation (CPAP/BiPAP), progressing to intubation and mechanical ventilation for the most severe cases.
ECMO (extracorporeal membrane oxygenation): For patients in refractory cardiogenic shock who do not respond to other measures, ECMO can bridge to recovery. Experience in South American centres has shown improved survival with ECMO in severe Andes virus HPS.
Vasopressors: For haemodynamic support when blood pressure cannot be maintained.
Ribavirin: Antiviral with some evidence of benefit for HFRS (the Old World form) but very limited evidence for HPS. Not routinely recommended but sometimes used given the lack of alternatives.
Who Should Seek Emergency Care?
If you have had potential rodent exposure in the past 6 weeks and develop any of the following, seek emergency medical care immediately:
- Fever with muscle aches and no upper respiratory symptoms
- Progressive shortness of breath or dry cough
- Feeling of tightness or heaviness in the chest
Do not wait to see if symptoms resolve. The window for intervention before the cardiopulmonary phase is narrow.
For a symptom checklist and more guidance, see the symptoms page. To understand your geographic risk, see the outbreak map.
Sources
- Zaki SR & Greer PW (1995). Hantavirus pulmonary syndrome — pathologic findings. American Journal of Pathology.
- MacNeil A & Nichol ST (2010). Epidemiology and pathogenesis of hantavirus pulmonary syndrome. Public Health Reports.
- CDC HPS Clinical Description
- WHO Hantavirus Fact Sheet
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