Hantavirus cardiopulmonary syndrome

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Hantavirus cardiopulmonary syndrome (HCPS) is a notifiable condition. Symptoms of early infection are nonspecific and can resemble many other febrile and respiratory illnesses. Therefore, early diagnosis is difficult. A history of peridomestic exposure to rodents or cleaning rodent-infested enclosures is an epidemiologic clue to diagnosing hantavirus infection. Contact with a known case of Andes virus (ANDV) infection during an outbreak is also relevant. It is important to consider hantavirus infection early in the differential diagnosis for patients with a relevant epidemiologic history. Serologic or molecular testing is required to confirm the diagnosis.

Infection prevention and control (IPC)

Standard precautions are recommended when managing all patients with hantavirus infection.[49][50]

Human-to-human transmission has been reported rarely with ANDV. If ANDV infection is suspected or confirmed, the patient should be placed in an isolation room, and contact and airborne precautions are recommended including use of a gown, eye protection, and a N95 (or higher-level) respirator when entering the patient’s room. Duration of precautions should be determined on a case-by-case basis in conjunction with local public health authorities.[51][6]

Stages of illness

HCPS infection is best understood as occurring in stages.[52]

Following virus exposure there is an asymptomatic incubation period. A prodromal nonspecific viral illness follows with fever, headache, myalgias, and often prominent gastrointestinal (GI) symptoms.
During an early pulmonary syndrome phase there is increasing dyspnea and hypoxemia.
In the cardiopulmonary phase the patient is gravely ill with pulmonary edema, thrombocytopenia, hemoconcentration, and cardiogenic shock.
In those survivors of the cardiopulmonary phase, there follows a diuresis phase with resolution of the pulmonary edema. Convalescence may be prolonged.

Clinical presentation

Prodromal illness

Diagnosis is rarely made at this stage of illness due to nonspecific symptoms. Prodromal viral illness symptoms including fever, headache, myalgia, and GI symptoms (e.g., anorexia, nausea, vomiting, diarrhea, abdominal pain) are usually present.[5]
Upper respiratory tract symptoms (e.g., sore throat, nasal congestion, sneezing), are rarely described with hantavirus infection and would tend to exclude the diagnosis.[5]
Clinically, the patient may be tachypneic, but oxygen saturations will be normal.

Early pulmonary phase

Progression of the disease results in increasing dyspnea with low oxygen saturations.

Cardiopulmonary phase

Progression of the disease results in hypotension and pulmonary edema.
Patients may have dyspnea, chest tightness, and a cough as the lungs fill with fluid.[6]
Late symptoms generally appear approximately 4 to 10 days after the initial phase of illness, with rapid deterioration over 24 hours. The critical phase is usually short.[6]

Diuresis phase

In survivors of the cardiopulmonary phase, there follows a diuresis phase with resolution of the pulmonary edema. Convalescence may be prolonged.

The incubation period is typically 9 to 33 days (median 14 to 17 days, and up to 3 weeks after rodent bite).[31][32] However, symptoms of HCPS caused by ANDV typically appear within 4 to 42 days after exposure.[6]

It should be noted that some patients with hantavirus infection may have milder illness without significant cardiopulmonary compromise.[51] Asymptomatic infection is thought to be rare in the US, but may be more common in Central and South America.[53][54][55][56][57] Patients are typically only infectious when they are symptomatic.[6]

Initial laboratory investigations

Specific investigations are usually not performed early in the illness. However, if a complete blood count (CBC) is performed for any reason (e.g., as part of the work-up of a nonspecific viral illness), it may provide an early clue to the diagnosis, as thrombocytopenia with a supporting epidemiologic history is suggestive of hantavirus infection.[58] The presence of thrombocytopenia in the prodromal phase may indicate the need for confirmatory hantavirus testing.[59]

All patients with compatible symptoms should have a CBC performed.

CBC will show thrombocytopenia with an elevated hemoglobin (Hb) and hematocrit (Hct) as evidence of hemoconcentration. There is an associated leukocytosis with juvenile forms (immunoblasts).[5]
The degree of thrombocytopenia may be prognostic of poor outcome.[10]

The presence of 4 out of the 5 following findings after the onset of pulmonary edema has a sensitivity of 96% and specificity of 99% for HCPS:[59]

Thrombocytopenia
Myelocytosis
Hemoconcentration
Lack of significant toxic granulation in neutrophils
More than 10% of lymphocytes with immunoblastic morphologic features.

The combination of at least 4 of these findings can guide early management decisions until results of confirmatory tests are available.[59]

Confirmatory laboratory investigations

Testing to confirm the diagnosis is recommended in all patients with compatible symptoms and a relevant epidemiologic history.[60]

Tests are typically available from local public health authorities, and consultation may be required for guidance on the type of testing to perform and the specimen types required. Specimens should be collected and handled according to local safety procedures.

Serologic testing is recommended to confirm the diagnosis.[51][60][61]

Enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig) M-capture and IgG serologies for hantavirus are recommended.
Detection of hantavirus-specific IgM, or rising titers of hantavirus-specific IgG, confirms the diagnosis.[62] By the time the symptoms are evident, patients uniformly have antibodies of IgM class and some have antibodies of the IgG class.

Detection of hantavirus RNA by reverse transcriptase polymerase chain reaction (RT-PCR) may also be used.[51][60][61][63]

RT-PCR is more sensitive in the early acute stages of illness (before antibodies appear), and is able to determine the specific species of hantavirus.
Identifying the species is important as enhanced IPC measures are required for ANDV infection due to the risk of human-to-human transmission.

Cruise ship outbreak 2026

Public health agencies have published specific guidance for testing cases associated with the MV Hondius cruise ship outbreak in May 2026.
The World Health Organization (WHO) recommends that any person who meets the operational case definition for a suspected or probable case should be tested.[64] See Criteria.
- RT-PCR testing on whole blood is recommended for confirmation of ANDV infection. If ANDV-specific assays are not available, sequencing is recommended to confirm the virus species.
- ELISA or indirect immunofluorescence assay (IFA) may also be used to confirm the diagnosis in acute infection. However, the potential cross-reactivity with cocirculating hantaviruses should be considered, depending on local epidemiology.
- Testing of asymptomatic high-risk contacts may be considered if resources allow.
The Centers for Disease Control and Prevention (CDC) recommends considering ANDV infection in patients who have compatible symptoms and who were aboard the MV Hondius cruise ship or had direct contact with someone associated with the cruise ship virus outbreak.[65]
- Suspected cases should be immediately reported to state, tribal, local, or territorial health departments, and advice obtained on diagnostic testing.

A negative result does not rule out the diagnosis, particularly in the first 72 hours. Repeat testing should be considered 24 to 48 hours later (or up to 72 hours after, depending on guidance) if the clinical suspicion is high but initial testing is negative.[64][66]

Combining serology with RT-PCR is highly sensitive and represents a desirable approach to the laboratory diagnosis of HCPS, where available.[67]

Investigations during cardiopulmonary phase

Once the cardiopulmonary phase begins, the disease can progress rapidly to cardiogenic shock and death and must be managed in an intensive care unit.[47]

All patients should have a CBC, arterial blood gas (ABG), and serum lactate performed.

CBC shows hemoconcentration, as indicated by an elevated Hb and Hct.[59] This is a marker for capillary leak.
ABG shows metabolic acidosis.[47]
Elevated serum lactate levels are a marker of poor outcome.[68][69]

Cardiac evaluation is also required.

ECG may show arrhythmias ranging from a sinus bradycardia to ventricular fibrillation.
Echocardiogram will show depressed cardiac ejection fraction.

Hemodynamic monitoring is important. The hemodynamic pattern of HCPS is not identical to septic or cardiogenic shock, and presents specific temporal patterns.[69]

During the cardiopulmonary phase, a decreased cardiac index and increased peripheral resistance is seen, distinguishing the shock from septic shock, which has a low systemic resistance and high cardiac output. Peripheral resistance and cardiac index is assessed using a flow-directed pulmonary artery catheter (Swan-Ganz catheter). Alternative methods (e.g., transpulmonary thermodilution catheter) may be available in specialist centers. A cardiac index of <2.5 L/minute/m² is one of the criteria for instituting extracorporeal membrane oxygenation (ECMO).[52][70][69][68]

Lung biopsy may be performed either transbronchially at bronchoscopy or by video-assisted thoracoscopic surgery in patients with unexplained rapidly progressive pulmonary disease.[70][71]

In cases of HCPS it will show intra-alveolar edema with an interstitial infiltrate of immunoblasts. There will be scant polymorphonuclear cells. Endothelial and alveolar lining cells are intact and appear normal.
Immunohistochemical staining for hantavirus RNA is available as a research test through the CDC and will show diffuse endothelial cell staining.

Imaging

All patients with respiratory symptoms should have a chest x-ray (CXR) performed.[5][72]

In the early pulmonary phase, CXR may be normal or suggestive of early interstitial edema.
In the cardiopulmonary phase, CXR shows evidence of progressive noncardiogenic pulmonary edema (the heart size remains normal and pulmonary infiltrates with or without pleural effusion may be present).[Figure caption and citation for the preceding image starts]: Bilateral fluffy pulmonary infiltrates in hantavirus pulmonary syndromeCDC Public Health Image Library (PHIL), Loren Ketai, MD [Citation ends].

Emerging investigations

Hantavirus isolation in cell culture is not routinely recommended for laboratory diagnosis. Virus isolation requires specialized expertise and Biosafety 3 laboratory facilities. Nevertheless, ANDV has been isolated in cell culture from the blood of patients and from organs of those with fatal disease.[4]

There are currently no antigen-based rapid diagnostic tests available.

Differential diagnosis

Symptoms of early infection are nonspecific and can resemble many other febrile and respiratory illnesses, and the differential diagnosis is broad. Testing for more common illnesses (e.g., influenza, coronavirus disease 2019 [COVID-19], and other common causes of febrile and gastrointestinal illnesses) is recommended in an acutely unwell patient with epidemiologic risk factors and compatible symptoms.[6]

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