Viral Pathogens

Let’s embark on a tour of some of the most important villains in the viral world. When we perform infectious disease serology, we’re essentially acting as immunological detectives. We’re sifting through the patient’s serum—the liquid portion of their blood—for clues that tell a story. This story is about the ongoing or past battles between the patient’s immune system and a specific pathogen

Our main clues are antibodies. We are primarily looking for two classes: * IgM: This is the “first responder.” IgM antibodies are the first to appear after a new infection. Their presence usually signals a current or very recent acute infection. They are the alarm bells ringing now * IgG: This is the antibody of memory. IgG antibodies appear after IgM and typically persist for life, providing long-term immunity. Their presence usually indicates a past infection or vaccination. They are the historical record of a battle won

Sometimes, we also look for pieces of the virus itself, called antigens, which tell us the virus is physically present. By strategically looking for the right combination of IgM, IgG, and antigens, we can determine if a patient is currently sick, immune, or has a chronic infection

Let’s apply these principles to some of the most common viruses you’ll encounter

Hepatitis Viruses: Attackers of the Liver

Hepatitis simply means inflammation of the liver. While several viruses can cause it, we’ll focus on the big three: A, B, and C. Their modes of transmission and clinical outcomes are vastly different, and their serological profiles are unique

Hepatitis A Virus (HAV)

• Epidemiology & Significance: This is the “get it and get over it” virus. It’s transmitted via the fecal-oral route, often through contaminated food or water. It causes an acute bout of hepatitis (jaundice, fatigue, nausea) but never becomes chronic. There is a very effective vaccine available
• Laboratory Serology: The diagnosis is straightforward
  • Anti-HAV IgM: The presence of IgM antibodies to HAV is the definitive marker of an acute Hepatitis A infection. If this test is positive, the patient has hepatitis A right now
  • Total Anti-HAV (IgM and IgG): If this test is positive but the Anti-HAV IgM is negative, it means the patient only has IgG. This indicates immunity due to a past infection or vaccination. They are not currently sick and are protected

Hepatitis B Virus (HBV)

• Epidemiology & Significance: This is the most complex of the hepatitis viruses, both clinically and serologically. It is transmitted through blood and body fluids (sexual contact, IV drug use, perinatal). It can cause an acute infection, but it can also lead to a chronic infection that dramatically increases the risk for cirrhosis and liver cancer. There is also an excellent vaccine
• Laboratory Serology: We never order just one test for HBV; we order a panel to piece together the full story
  • Hepatitis B Surface Antigen (HBsAg): This is a protein from the surface of the virus itself. It is the first marker to appear and its presence indicates that the patient is currently infected and infectious. This is the key marker of an active acute or chronic infection
  • Anti-Hepatitis B Surface Antibody (Anti-HBs or HBsAb): This is the antibody of immunity and protection. Its presence (in the absence of HBsAg) means the person is immune, either from resolving a past infection or, most commonly, from vaccination. This is the antibody we want to see after a vaccine series
  • Total Anti-Hepatitis B Core Antibody (Total Anti-HBc): This antibody is directed against a core protein of the virus. It is a marker of exposure to the actual virus and appears in both acute and chronic infections, persisting for life. Critically, it is not produced in response to the vaccine. This is how we distinguish natural immunity (Anti-HBs positive and Anti-HBc positive) from vaccine-induced immunity (Anti-HBs positive and Anti-HBc negative)
  • Anti-HBc IgM: This specific IgM antibody is the key marker for an acute HBV infection

Hepatitis C Virus (HCV)

• Epidemiology & Significance: The “silent epidemic.” Like HBV, it’s transmitted via blood. A very high percentage of people who get HCV are unable to clear it and develop a chronic infection, which is often asymptomatic for decades while slowly destroying the liver. It is a leading cause of liver transplantation. There is no vaccine, but there are now excellent antiviral cures
• Laboratory Serology & Molecular Testing: This is a two-step process
  1. Screening Test: Anti-HCV Antibody. A positive result on this screening test means the patient has been exposed to HCV at some point. However, it cannot distinguish between a current, active infection and a past infection that the body has cleared
  2. Confirmatory Test: HCV RNA by PCR. This is a molecular test that looks for the virus’s genetic material. If this test is positive, it confirms the patient has an active, current HCV infection and requires treatment. If it is negative, it means the patient has cleared the virus

Herpesvirus Family: The Infections That Last Forever

This family of viruses (including VZV, EBV, and CMV) are masters of latency. After the primary infection, they hide out in your cells for life and can reactivate later, especially if you become immunosuppressed

Varicella-zoster Virus (VZV)

• Epidemiology & Significance: This is the “two-for-one” virus of the herpes family, causing two distinct diseases
  1. Varicella (Chickenpox) This is the primary infection, usually occurring in childhood. It’s a highly contagious respiratory virus that causes the classic widespread, itchy vesicular rash
  2. Herpes Zoster (Shingles) This is the reactivation. After the chickenpox resolves, the virus doesn’t leave; it retreats into a dormant state, hiding out in the dorsal root ganglia (sensory nerve ganglia). Years or decades later, often due to waning immunity from age or immunosuppression, the virus can reactivate. It travels down a single nerve, causing a painful, unilateral rash in a specific band of skin called a dermatome. A highly effective vaccine exists for both chickenpox and shingles
• Laboratory Serology & Molecular Testing: The testing approach depends on the clinical question
  • Anti-VZV IgG: This is the most common VZV test performed. Its sole purpose is to determine immunity status. A positive IgG result indicates immunity from either a past infection (chickenpox) or vaccination. This is a critical test for healthcare workers, pregnant women, and pre-transplant patients
  • Anti-VZV IgM: The presence of IgM can suggest a recent primary infection (chickenpox) or, less reliably, a reactivation (shingles)
  • VZV DNA by PCR: This is the gold standard for diagnosing active disease. A swab from a skin lesion (vesicle fluid) or a CSF sample in cases of suspected neurological involvement is tested. This method is far more sensitive and specific than serology for confirming an active case of either chickenpox or shingles

Epstein-Barr Virus (EBV)

• Epidemiology & Significance: This is the virus that causes Infectious Mononucleosis (mono), the “kissing disease.” It is incredibly common, and most people are infected by adulthood
• Laboratory Serology
  • Monospot Test: A rapid screening test that detects heterophile antibodies—non-specific IgM antibodies that are produced during mono and happen to cross-react with animal red blood cells. It’s fast, but it can be negative early in the disease and in young children
  • EBV-Specific Panel: This is the definitive test
    • Anti-Viral Capsid Antigen (VCA) IgM: The best marker for a primary, acute EBV infection
    • Anti-VCA IgG: Appears along with the IgM but persists for life, indicating a past infection
    • Anti-EBV Nuclear Antigen (Anti-EBNA): This is the crucial “late” antibody. It only appears after the acute infection is over (in convalescence)
  • Putting it together
    • Acute Mono: VCA-IgM positive, VCA-IgG positive, Anti-EBNA negative
    • Past Infection: VCA-IgM negative, VCA-IgG positive, Anti-EBNA positive

Cytomegalovirus (CMV)

• Epidemiology & Significance: Another extremely common herpesvirus that is usually asymptomatic in healthy individuals. The danger is in two populations:
  1. Immunocompromised Patients Especially transplant recipients, in whom CMV reactivation can be a life-threatening disease
  2. Congenital Infection A primary CMV infection in a pregnant woman can be transmitted to the fetus and cause serious birth defects
• Laboratory Serology & Molecular Testing
  • Anti-CMV IgG & IgM: Used to determine exposure status. A positive IgG is very common in adults. A positive IgM can indicate a primary infection or reactivation
  • CMV DNA by PCR (Viral Load): This is the most important test for managing immunocompromised patients. We don’t just care if they have the virus (their IgG will be positive); we need to know if it’s actively replicating. We monitor their viral load to decide when to start and stop antiviral therapy

Childhood Viruses & Immunity

For these viruses, the primary role of serology today is not to diagnose acute disease, but to verify immunity status, especially in pregnant women or healthcare workers

Rubella Virus (“German Measles”)

• Epidemiology & Significance: A generally mild respiratory virus. Its entire clinical importance rests on the devastating effects of Congenital Rubella Syndrome (CRS). If a non-immune woman is infected during the first trimester of pregnancy, the virus can cause severe birth defects including deafness, blindness, and heart problems
• Laboratory Serology: The goal is to prove immunity
  • Anti-Rubella IgG: A positive IgG test result demonstrates that a person is immune to rubella, thanks to the highly effective MMR (Measles, Mumps, Rubella) vaccine. This is the desired result for any woman of child-bearing age

Measles (Rubeola)

• Epidemiology & Significance: A highly contagious respiratory virus that can cause severe disease with complications like pneumonia and encephalitis. Due to decreased vaccination rates, outbreaks are becoming more common
• Laboratory Serology
  • Anti-Measles IgM: Used by public health labs to confirm an acute measles infection during an outbreak investigation
  • Anti-Measles IgG: Used to verify the immunity status of healthcare workers or others who may have been exposed and have an uncertain vaccination history

Human Immunodeficiency Virus (HIV)

• Note: The serology and monitoring of HIV are so extensive that we cover them in detail under Acquired Immunodeficiency. As a brief summary for this section, modern diagnosis relies on a 4th generation combination immunoassay that detects both HIV antibodies and the p24 antigen, closing the diagnostic window period and allowing for very early detection of infection