Updated: Feb 02, 2022
  • Author: Martha L Muller, MD, MPH; Chief Editor: Michael Stuart Bronze, MD  more...
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Coxsackieviruses belong to the family Picornaviridae and the genus Enterovirus, which also includes poliovirus and echovirus. Enteroviruses are among the most common and important human pathogens. Coxsackieviruses share many characteristics with poliovirus. With control of poliovirus infections in much of the world, more attention has been focused on understanding the nonpolio enteroviruses such as coxsackievirus.

Coxsackieviruses are nonenveloped viruses with linear single-stranded RNA. Coxsackieviruses are divided into group A and group B viruses based on early observations of their pathogenicity in mice. Group A coxsackieviruses were noted to cause a flaccid paralysis, which was caused by generalized myositis, whereas group B coxsackieviruses were noted to cause a spastic paralysis due to focal muscle injury and degeneration of neuronal, pancreatic, and myocardial tissue. At least 23 serotypes (1-22, 24) of group A and 6 serotypes (1-6) of group B are recognized.

In general, group A coxsackieviruses tend to infect the skin and mucous membranes, causing herpangina, acute hemorrhagic conjunctivitis (AHC), and hand-foot-and-mouth (HFM) disease. Group B coxsackieviruses tend to infect the heart, pleura, pancreas, and liver, causing pleurodynia, myocarditis, pericarditis, and hepatitis. Both group A and group B coxsackieviruses can cause nonspecific febrile illnesses, rashes, upper respiratory tract disease, and aseptic meningitis.

Numerous group A coxsackieviruses are responsible for causing CNS disease similar to poliomyelitis. Systemic neonatal disease is often associated with group B coxsackieviruses.

The development of insulin-dependent diabetes (IDDM) has recently been associated with recent enteroviral infection, particularly coxsackievirus B infection. This relationship is currently being studied further.

The Centers for Disease Control and Prevention (CDC) have rigorously evaluated cases of acute flaccid myelitis (AFM) since 2014, when an increased number of cases were reported. AFM is a CNS disease that specifically affects the spinal cord gray matter, causing muscle and reflex weakness. Most reported AFM cases do not have an identified etiologic pathogen. However, coxsackievirus A16 has been one of the viruses recovered from spinal fluid in a small number of confirmed cases.



Coxsackieviruses are transmitted primarily via the fecal-oral route and respiratory aerosols, although transmission via fomites is possible. The viruses initially replicate in the upper respiratory tract, particularly the tonsils, and the distal small bowel (Tyring). This results in viremia with dissemination and replication in various locations, which then results in symptoms. [1] Central nervous system (CNS) invasion is proposed to occur from viral migration along peripheral and central nerves into the CNS. [1]  They have been found in the respiratory tract up to 3 weeks after initial infection and in feces up to 8 weeks after initial infection. The viruses have been found to replicate in the submucosal lymph tissue and disseminate to the reticuloendothelial system. Further dissemination to target organs occurs following a secondary viremia. Innate, humoral and cell-mediated immunity all play a role in enteroviral response. [2]  However, enteroviral infections are often eradicated before antibody production occurs. [2]  




United States

Approximately 10 million symptomatic enteroviral infections are estimated to occur annually in the United States. From 2002-2004, an estimated 16.4%-24.3% of these illnesses were attributed to coxsackievirus serotypes. For 2 of the 3 years, coxsackievirus B1 was the predominant serotype. Enteroviruses are responsible for approximately 30,000 to 50,000 hospitalizations per year. The CDC found that coxsackievirus infections accounted for approximately 25% of all neonatal enterovirus infections (26,737) from 1983 to 2003. Those due to coxsackievirus B4 were associated with a higher mortality rate than any other serotype.

The CDC reports coxsackievirus A16 as the virus most frequently isolated in hand-foot-and-mouth disease (HFMD). Similarly, coxsackievirus A6 was the most frequently reported enterovirus from 2009-2013.


Coxsackievirus infections have worldwide distribution. They can be isolated year-round in tropical climates, with a decreasing incidence of disease and seasonality in areas of higher latitude.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Co-infections

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has significantly impacted the epidemiology of other respiratory viral pathogens. [3]  Respiratory enterovirus, in addition to rhinoviruses, have been reported as predominant compared to other respiratory viruses in patients with concurrent SARS-CoV-2 infection. [4]   Additionally, mild COVID-19 infection has been reported in those with co-infection with both species. [4]  The circumstances surrounding the continued circulation of these viruses during the pandemic have not been well delineated, but transmission properties and prolonged organism survival may play pivotal roles. [3]


Mortality due to coxsackievirus infection is uncommon. Neonates and immunocompromised individuals are at most risk for complications secondary to all enteroviral infections.


During the first decade, enteroviral infections are more common in males, with a male-to-female ratio of 2:1. The reason for this increased incidence is not well known.


Coxsackievirus infection occurs in all age groups but is more common in young children and infants. Children are at higher risk of infection during the first year of life. The rate of illness decreases greatly following the first decade of life.



In general, the prognosis is very good, with 90% of patients having no symptoms or experiencing mild, self-limited, nonspecific febrile illnesses or rashes.


Patient Education

Patients should be aware of the need for good hygiene practices to avoid transmission.

Patients need to be reassured that they have a self-limited viral illness that does not require any antibiotics for treatment.