When the body’s defense system is weakened, even germs that healthy people easily fight off can become serious threats. Understanding infections in people with compromised immune systems is essential for protecting those who are most vulnerable to illnesses that others might never notice.
What Does It Mean to Be Immunocompromised?
Being immunocompromised means that your immune system is not working as well as it should to fight off infections. This condition is also called having a weakened or suppressed immune system. Close to 7 million people in the United States have immune systems that don’t work well or at all, although the actual number could be even higher. These individuals face unique challenges because their bodies cannot respond normally to infections that healthy immune systems usually overcome.[1][2]
The immune system is made up of organs, tissues, and cells throughout the body, including the spleen, tonsils, bone marrow, and white blood cells (proteins that fight germs). In a normally functioning immune system, white blood cells remember all microbes that enter the body and fight those they don’t recognize, keeping you from getting sick. When this system is compromised, it may mount a weak response or no response at all to foreign substances, leaving people at much greater risk of infection.[5]
Host defense from infection depends upon a complex integrated system of physical barriers like skin and stomach acid, innate immunity (rapid responses by cells such as neutrophils and macrophages), and adaptive immunity (specific responses by B and T lymphocytes that improve with repeated exposure to antigens). An individual may have deficiencies of one or more components of host defense, but because each functional compartment of the immune system plays a specialized role, defects in specific functions lead to increased susceptibility to specific pathogens.[1]
Who Gets Infections When Immunocompromised?
Anyone can become immunocompromised, and the reasons vary widely. Some people are born with conditions that weaken their immune system, while others develop immunosuppression throughout their lives. The types of immunocompromising conditions can be divided into two main categories: congenital conditions that affect the fetus and newborn, and acquired conditions that develop later in life.[2]
Congenital conditions include genetic syndromes, B-cell defects, combined B-cell and T-cell defects, T-cell defects, phagocyte deficiency or dysfunction, and complement deficiencies. These conditions are present from birth and affect how the immune system develops and functions from the very beginning of life.[2]
Acquired conditions that compromise immunity are more common and can affect anyone at any age. These include diseases like cancer (especially leukemia, lymphoma, and multiple myeloma), HIV infection, diabetes, autoimmune diseases, sickle cell disease, liver cirrhosis, and viral hepatitis. Certain medical treatments also suppress the immune system, including chemotherapy, radiation therapy, immunotherapy, and long-term use of corticosteroids. People who have received organ or bone marrow transplants must take medications that deliberately suppress their immune system to prevent organ rejection.[2][4]
Some people have a weakened immune system for just a limited time, while others live with this situation on a long-term or permanent basis. Short-term immunosuppression can occur in people receiving chemotherapy or radiation for cancer, those taking steroids for conditions like asthma or rheumatoid arthritis, people with severe burns, those who are malnourished, or individuals who drink too much alcohol. Long-term immunosuppression affects people without a spleen, those with chronic diseases like AIDS or lupus, organ transplant recipients, older adults, and very young babies, especially those born prematurely.[5]
Causes of Infections in Immunocompromised People
Infections in immunocompromised individuals are caused by the same germs that affect everyone else, but the weakened immune system cannot fight them off effectively. The body’s immune system uses a number of defenses to prevent or get rid of infection, which can be caused by bacteria, viruses, fungi, or parasites. When these defenses are weakened, even organisms that are harmless to healthy individuals can become life-threatening.[3]
Several factors contribute to why immunocompromised people are more susceptible to infections. The breakdown of physical barriers like the skin or the lining of the mouth and gastrointestinal tract can occur as a side effect of medicine or radiation used for cancer treatment. Lower numbers of infection-fighting cells, particularly white blood cells, can be caused by certain cancers or as a side effect of medicines used for cancer treatment. The presence of foreign objects such as venous catheters (tubes placed in veins) or urinary catheters also increases infection risk, as these devices provide pathways for germs to enter the body.[3]
Different types of immune defects predispose people to different kinds of infections. B-cell defects make patients vulnerable to frequent respiratory tract infections and infections with certain viruses like parvovirus B19 and rotavirus. Combined B-cell and T-cell defects leave people susceptible to almost any organism, and these patients often present with failure to thrive, thrush, and Pneumocystis jirovecii infection. T-cell defects predispose to infections with Candida species, Mycobacterium avium-intracellulare complex, herpesviruses, and P. jirovecii. Phagocyte deficiency makes people vulnerable to Staphylococcus aureus, Pseudomonas aeruginosa, and fungal infections. Complement deficiency is associated with recurrent infections due to encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis.[2]
Risk Factors for Severe Infections
Certain groups of people face higher risks when immunocompromised. Older adults naturally experience weakening of their immune systems as they age, making them more vulnerable to infections. Very young children, especially premature babies, have immature immune systems that haven’t fully developed their defenses yet. These age-related factors mean that the very young and the very old require extra protection from infectious diseases.[5]
Malnutrition significantly weakens the immune system. Among malnourished infants and children, infectious diarrhea, pneumonia, tuberculosis, measles, malaria, salmonellosis, P. jirovecii infection, and HIV infection are common causes of death. The body needs adequate nutrition to produce the cells and proteins necessary for immune function, so those who don’t receive proper nutrition cannot mount effective immune responses.[2]
People taking certain medications face increased infection risks. Rituximab, a B-cell depleting monoclonal antibody frequently used for oncological, rheumatological, and neurological conditions, can significantly increase the risk of severe outcomes from infections. Similar drugs include ocrelizumab, veltuzumab, and ublituximab. According to a recent case series from the Centers for Disease Control and Prevention, 4 out of 5 patients using rituximab who were diagnosed with certain viral diseases died. Those who survived often had long-term disabilities such as cognitive and motor dysfunction.[9]
Environmental exposures also increase infection risk. Contact with soil, which contains bacteria and mold, could lead to fungal infections in immunocompromised individuals. Pet waste may carry parasites like Toxoplasma gondii or cryptosporidium that can cause serious illness in those with weakened immune systems. Even activities that are safe for healthy people, like swimming in pools or natural bodies of water, can pose risks because water may contain organisms that immunocompromised people cannot fight off.[14]
Symptoms of Infections in Immunocompromised Hosts
Getting sick frequently or having unusually long-lasting infections are the most common signs of having a compromised immune system. However, getting sick often on its own doesn’t necessarily mean the immune system isn’t working properly. The kind of illnesses someone gets matters more than how frequently they occur. For instance, young children getting colds all the time is completely normal and doesn’t indicate immune problems.[4]
The usual symptoms of infection may be absent or different in immunocompromised patients. These individuals may not show the classic signs of infection such as redness and swelling at the infection site. Sometimes the only symptom of an infection may be fever. This makes it harder to recognize when an infection is present and requires immediate medical attention.[3]
When immunocompromised people do get sick, several patterns emerge. They get illnesses that most people fight off without even getting sick. Illnesses that mildly affect most people make them severely sick. Illnesses linger, or it takes a longer time to recover from being sick. They are more likely to develop complications than others, such as getting pneumonia after having a respiratory virus. They might be more likely to get sick again with certain viral infections they’ve had in the past, like Epstein-Barr virus or varicella-zoster virus.[4]
Certain specific infections should raise suspicion of a compromised immune system. These include Pneumocystis pneumonia, symptomatic cytomegalovirus infections, fungal infections that spread to other areas of the body outside of the lungs, frequent bacterial infections, and frequent or long-lasting illness with pneumonia, herpes simplex, campylobacter, or cyclosporiasis. Healthcare providers use the presence of these particular infections to help identify patients who may have underlying immune system problems.[4]
In patients with immunosuppression who develop infections, the clinical presentation often includes fever followed by development of neurological signs and symptoms, such as confusion, tremors, focal neurologic deficits, ascending paralysis, progressive dementia, unresponsiveness, or coma. Although most patients develop symptoms during summer and fall when certain disease-carrying insects are most active, some patients may present outside of the typical season because of a prolonged or atypical clinical course.[9]
Why Infections Are More Dangerous
Infections pose greater dangers to immunocompromised individuals for several critical reasons. The infection may move quickly from fever alone to sepsis (a life-threatening condition where the body’s response to infection damages its own tissues) and death. In the absence of infection-fighting white blood cells, infections can rapidly progress. For this reason, patients with weak immune systems who have low white blood cell counts are asked to report if they have fever right away, and these patients are often hospitalized if they get a fever so they can receive treatment with intravenous antibiotics.[3]
Immunocompromised patients may have trouble clearing infections from their bodies. For example, a viral infection such as the flu may take longer to clear from a patient with a weak immune system compared to a person with a healthy immune system. This prolonged infection period means more time feeling sick, more opportunity for complications to develop, and greater risk that the infection will spread to other parts of the body.[3]
Infections can cause sepsis, a serious illness where instead of fighting the infection, the body starts to attack itself and the healthy cells and tissues. Sepsis can lead to severe sepsis and septic shock, conditions that can leave long-lasting health problems and can even cause death. The risk of developing sepsis is particularly high in immunocompromised individuals because their weakened immune systems respond abnormally to infections.[5]
The number of immunosuppressed patients continues to increase worldwide due to demographic development and improved long-term survival, including for patients under immunosuppression. A major cause of hospitalization and mortality among these patients are infections. Their management, including prevention and adequate treatment, plays a crucial role in survival and quality of life, but also with regard to economic factors.[8]
Prevention of Infections
Preventing infections in immunocompromised people requires multiple layers of protection. Hand hygiene stands as the most important preventive measure. Many infections are spread from bacteria or viruses that we pick up on our hands when we touch people or objects around us. Washing hands with soap and water for at least 20 seconds, making sure to clean under nails and between fingers, is the best way to prevent the spread of infection. If water isn’t available, a waterless hand sanitizer with alcohol can be used.[3][5]
Vaccination represents one of the best protections both patients and caregivers can have. According to guidelines from the Infectious Diseases Society of America, most immunocompromised patients should be vaccinated. Getting all vaccinations recommended by healthcare providers, including routine ones for measles, mumps, and rubella, as well as others for flu, COVID-19, and pneumonia, helps build whatever immune protection is possible. Care providers for patients with weak immune systems should also receive all recommended vaccinations, including influenza and pertussis vaccines.[2][5]
However, patients who are not vaccinated before a cancer diagnosis or before starting particular treatments may not be able to receive certain vaccines afterwards. This is because some vaccines contain weakened live viruses that could cause disease in severely immunocompromised individuals. If this is the case, it becomes even more important for everyone who will be coming in contact with the patient to be vaccinated, including spouses, caregivers, children, and others at home.[17]
Avoiding contact with people who are sick is essential. Even a common cold virus can make a patient with a weak immune system very sick. Immunocompromised individuals should try to minimize their time in crowded public places, especially during flu season, which generally peaks between December and February. Maintaining awareness of infection rates in the local area and practicing social distancing helps reduce exposure risk.[3][17]
Food safety requires special attention. Fresh fruits and vegetables should be washed thoroughly with running water, and hard-skinned items like potatoes and carrots should be scrubbed with a brush. Produce should never be soaked in the sink, which may harbor bacteria. Raw or lightly cooked sprouts should be avoided. Immunocompromised people should not eat raw fish, undercooked meats, rare burgers, uncooked eggs, soft cheeses like brie and Camembert, blue-veined cheeses, or uncooked deli meats. Self-serve buffets and salad bars also pose risks and should be avoided.[14]
Protection from environmental hazards matters too. Insect repellent with effective ingredients like DEET or picaridin should be used before going outdoors, along with protective clothing. Wooded and brushy areas should be avoided when possible. After outdoor activities, both people and pets should be checked for ticks. Soil contains bacteria and mold that could lead to fungal infections, so gardening gloves should be worn to guard against cuts and scrapes. Long pants and long sleeves provide additional protection. In some cases, doctors may recommend avoiding contact with soil entirely.[14]
Pet care requires special precautions. Pet waste should be handled carefully using gloves, or someone else should clean litter boxes or cages. Hands must be washed thoroughly afterward. It’s best to stay away from reptiles, amphibians, and farm animals, as they can carry organisms that are particularly dangerous for immunocompromised individuals.[14]
Water safety cannot be overlooked. Even chlorinated water and saltwater can contain organisms that cause illness. Immunocompromised people should never swallow water when swimming in pools, lakes, rivers, or oceans. Drinking from springs or private wells should be avoided. Depending on water quality in the area, even tap water and ice made with it could be risky. In some cases, it may be best to drink only bottled water or use a water filter.[14]
Cleaning any breaks in the skin immediately and keeping them clean until healed helps prevent infections from entering through damaged skin barriers. Using antiseptic solutions and keeping wounds covered protects against bacterial invasion.[5]
How the Body’s Defense System Changes
Understanding what happens in the body when immunity is compromised helps explain why infections become so dangerous. The immune system normally works through two main compartments: innate immunity and adaptive immunity. Innate host defense mechanisms are rapid, taking only minutes to hours to respond. They depend upon patterned responses to pathogens by cells like neutrophils and macrophages, along with the complement system. These defenses don’t improve with repeated exposure to pathogens.[1]
Adaptive immune mechanisms are slower, taking days to develop, but they are highly specific to individual antigens. B lymphocytes and T lymphocytes provide this type of immunity, and their responses improve with repeated exposure to an individual antigen through the development of memory cells. Successfully integrated and functioning together, physical barriers and the components of innate and adaptive immunity form a critical system necessary for defense against infection and the generation of normal inflammatory responses.[1]
When any part of this system fails, specific vulnerabilities emerge. B lymphocytes produce antibodies that neutralize pathogens in the blood and body fluids. When B-cell function is impaired, patients cannot produce adequate antibodies, leaving them vulnerable to bacteria that circulate in the bloodstream and to certain viruses. T lymphocytes coordinate immune responses and directly kill infected cells. When T-cell function is compromised, patients become susceptible to intracellular pathogens that hide inside cells, including certain bacteria, viruses, fungi, and parasites.[1]
Phagocytic cells like neutrophils and macrophages engulf and destroy pathogens. When these cells are reduced in number or don’t function properly, bacteria and fungi that would normally be quickly eliminated can establish infections. The complement system consists of proteins that mark pathogens for destruction and directly damage bacterial membranes. Deficiencies in complement components leave people vulnerable to bacteria with protective capsules.[1]
Physical barriers provide the first line of defense. The skin keeps pathogens out, stomach acid kills swallowed organisms, and the mucous membranes of the respiratory tract trap and remove inhaled particles. When these barriers are breached by catheters, damaged by chemotherapy, or compromised by surgery, pathogens gain direct access to internal tissues where they can cause serious infections.[1]
Patients with combined defects in multiple parts of the immune system face the greatest risks. Those with combined B-cell and T-cell defects can be infected by almost any organism and often present with failure to thrive, persistent thrush in the mouth, and unusual infections that healthy people almost never get. Other commonly seen pathogens in these patients include Streptococcus pneumoniae, Pseudomonas aeruginosa, Legionella pneumophila, Listeria monocytogenes, Nocardia species, Mycobacterium species, fungi, varicella-zoster virus, herpes simplex virus, cytomegalovirus, Epstein-Barr virus, respiratory viruses, Toxoplasma species, cryptosporidia, Strongyloides species, and other encapsulated bacteria.[2]