Norovirus in Immunocompromised Host - Closer Look at a Potentially Lethal Infection

Introduction

Norovirus is considered the most predominant cause of acute infections such as non-bacterial gastroenteritis globally and results in a significant economic burden in developed countries like the United States. Studies show that noroviruses are responsible for increased mortality among children below the age of five years in developing countries. These infections occur as sporadic outbreaks, especially in closed settings such as healthcare facilities. Noroviruses cause gastroenteritis in both immunocompetent as well as immunocompromised hosts. Noroviral gastroenteritis is often characterized as a self-limiting infection in immunocompetent individuals that gets cured within two days of illness.

On the contrary, these viruses lead to persistent infection in immunocompromised individuals, usually lasting from several weeks to years, thereby complicating clinical management. Understanding the potential impact of norovirus in immunocompromised hosts helps in better therapeutic intervention and prevention of these infections in the susceptible population.

What Is Meant by an Immunocompromised Host?

Immunocompromised host refers to those individuals whose immune systems are defective or compromised due to diverse clinical conditions. Such individuals have deficient defense mechanisms to fight infections compared to normal people. This delicate condition makes immunocompromised persons more susceptible to infection with common pathogens that do not otherwise produce diseases in normal (immunocompetent) people. Some of the common factors that render an individual an immunocompromised host are as follows -

• Immunologic disorders such as human immunodeficiency virus (HIV) infection.

• Individuals who have received organ transplants and are under immunosuppressive medications.

• Patients with severe neutropenia for prolonged duration (absolute neutrophil count is less than or equal to 500 cells/mL).

• Immunosuppressive therapies like radiation therapy, cytotoxic chemotherapeutic agents, anti-rejection medications, and steroid treatments.

• Chronic systemic diseases like diabetes, emphysema, cardiac failure, and cancer.

• Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

• Congenital immune deficiency syndrome.

• Children with blood malignancies like acute lymphoblastic leukemia who are under chemotherapy.

Immunocompromised hosts are recognized as high-risk individuals who have an increased risk of acquiring airborne and waterborne infections. They show greater susceptibility to pathogenic attack and enhanced potential for developing serious complications associated with infections. In immunocompromised hosts, vaccination response is greatly reduced, which makes them more prone to vaccine-preventable infections when compared to immunocompetent individuals.

What Is the Correlation Between Norovirus and Immunocompromised Host?

Noroviruses are minute, nonenveloped RNA viruses primarily isolated during global outbreaks causing acute gastroenteritis. Noroviruses pose an immediate threat to healthcare settings causing nosocomial infections, which are attributed to their contagious mode of transmission and high resistance to disinfectants.

These viruses cause acute self-resolving gastroenteritis in normal healthy individuals where the illness gets cured within a few days, and only supportive measures are needed. Whereas in immunocompromised hosts, norovirus establishes a chronic and persistent infection leading to prolonged virus shedding and associated gastrointestinal illness, which causes considerable debilitating and life-threatening complications over some time. In recent years, various clinical studies have been conducted to understand the mechanisms of norovirus in inducing chronic infection among immunocompromised hosts. Some of the proven scientific facts about the behavior of norovirus in immunocompromised hosts are as follows -

• Cellular immunity (mainly T lymphocytes) is the prime defense mechanism for the clearance of norovirus in the human body.

• In immunocompromised hosts, both cellular and humoral (antibodies) immunity are suppressed, making them more vulnerable to norovirus infection.

• This reduced immune activity impairs the ability to neutralize and transport norovirus particles.

• Also, most immunosuppressant treatments cause T-cell depletion, which further increases the susceptibility to norovirus infection.

• Incomplete clearance of norovirus causes prolonged shedding of viral particles in immunocompromised hosts, and also they become reservoir hosts for norovirus. However, the infectivity of the viral particle in long-term shedding is still under research.

• The immature immune system in neonates and newborns is also responsible for increased norovirus infection susceptibility.

What Are the Clinical Manifestations of Norovirus in Immunocompromised Hosts?

Norovirus causes asymptomatic or mild to moderate infections in normal people. However, it leads to severe complications in immunocompromised hosts. Some of the clinical manifestations of norovirus infection in immunocompromised individuals are as follows -

• Acute onset of diarrheal illness with indefinite duration.

• Viral shedding occurs over weeks to years.

• Persistent gastroenteritis.

• Intestinal barrier dysfunction.

• Malnutrition.

• Dehydration.

• Fever.

• Protracted diarrhea is frequently seen in infants.

• Increased morbidity.

• Extended hospital stay or prolonged hospitalizations.

• Excessive weight loss.

• Fatal complications such as acute renal failure and arrhythmia lead to death.

How Is Norovirus Detected in Immunocompromised Hosts?

Detecting norovirus in the immunocompromised host is often challenging because of the overlapping between actual clinical symptoms with that of asymptomatic norovirus shedding. Also, the initial lack of clinical suspicion delays the testing protocols for norovirus infections. Defective cellular immunity, improper noroviral clearance, and gastrointestinal problems due to other disorders contribute to diagnostic challenges in such individuals. Some of the currently employed diagnostic methods are as follows -

• Molecular techniques like nested polymerase chain reaction (PCR) detect norovirus RNA during the first set of amplification cycles.

• Further amplification using real-time PCR markedly detects the viral load and helps differentiate asymptomatic carriers from actual clinical norovirus infection.

• Numerical quantitative estimation of noroviral loads is considered an objective marker of the infection.

• Initial screening tests include detecting viral particles through electron microscopy, which is often considered an insensitive assay and also delays diagnosis.

• Reverse-transcription PCR is a qualitative assay that detects viral RNA and has recently been the gold standard for norovirus diagnosis.

• Clinical suspicion of susceptible groups like immunocompromised hosts, children, travelers, and elderly people with comorbid conditions helps in the early detection of norovirus.

How Is Norovirus Treated in Immunocompromised Hosts?

To date, no virus-specific therapeutic interventions are available for norovirus infections. Supportive care and modifications in immunosuppressive therapies help in relieving clinical symptoms. Some of the treatment strategies for norovirus infections in immunocompromised individuals are as follows -

• Enteral or parenteral nutritional supplements to compensate for chronic diarrheal illness.

• Immunocompromised individuals infected with norovirus would be hospitalized for an average of 73 days.

• Immunosuppressive regimens are reduced or temporarily stopped to remove the viral load and cure protracted gastroenteritis. However, their primary medical conditions, such as the functioning of transplanted organs and graft tissue integrity, should be continuously monitored.

• Various research and clinical studies are being carried out in developing norovirus antivirals. Interferon (IFN), Rupintrivir, and nucleoside analogs are widely used to manage norovirus infections.

• Norovirus vaccines are not yet developed. However, the effectiveness of vaccines in immunocompromised individuals is still questionable.

How to Prevent Norovirus Infections in Immunocompromised Hosts?

The increase in the likelihood of norovirus transmission among immunocompromised individuals, related complications, and associated potential outbreaks highlights the importance of preventing norovirus infections in these susceptible populations. Some of the preventive measures are as follows -

• Strict isolation precautions, such as contact isolation of suspected carriers, should be followed in healthcare settings to prevent the outbreak of nosocomial infections.

• Immunocompromised individuals must avoid contact with patients who are affected with gastroenteritis.

• They must avoid eating unsafe foods such as uncooked meats or eggs and egg products.

• Thorough washing of hands as well as the produce before eating and boiling water before consumption.

• Avoiding contact with potential surfaces that are feces-contaminated, such as toilet seats.

• Immunocompromised individuals seeking medical care or needing organ transplantation abroad must be aware of the high-risk endemic areas and should refrain from visiting such areas.

Conclusion

Noroviruses cause serious complications in immunocompromised individuals because of reduced immune response. They lead to persistent infections and also challenge diagnostic interventions. Advanced molecular assays in immunocompromised hosts enhance early detection and management of norovirus infections.