Who is at High Risk for Severe West Nile Virus Illness?

Introduction: High Risk Groups for Severe West Nile Virus Illness

Most people who get infected with West Nile Virus never know it happened. No symptoms. No hospital. Life goes on. But for a specific group — older adults, the immunocompromised, organ transplant recipients, people with multiple sclerosis, blood transfusion recipients, diabetics, and others — West Nile Virus can spiral into something far more serious. Neurological. Life-altering. Sometimes fatal.

That gap between “mild nuisance” and “neurological emergency” is what makes understanding your personal risk so critically important — especially as WNV cases are rising again. According to the American Medical Association, West Nile virus deaths rose 32% in 2025, with the CDC actively working with multiple state health departments on transfusion-, transplantation-, and dialysis-related clusters.

This article lays out — clearly and completely — every recognized high-risk group for severe West Nile Virus illness, backed by the latest evidence, including a major 2025 JAMA Network Open study analyzing over 3,000 real-world WNV cases. Some of what’s on this list may genuinely surprise you. Keep reading.

Understanding West Nile Virus: What You Need to Know First

West Nile Virus (WNV) is a mosquito-borne flavivirus, primarily transmitted through the bite of an infected Culex mosquito. First detected in the U.S. in 1999, it has since spread to all 48 contiguous states. Birds serve as reservoir hosts; mosquitoes pick up the virus by feeding on infected birds, then pass it to humans and other mammals.

Three clinical presentations define WNV infection:

1. Asymptomatic infection — roughly 80% of all cases. No symptoms at all.
2. West Nile fever — fever, headache, body aches, fatigue, occasional rash. Usually resolves in days to a few weeks.
3. Neuroinvasive disease — encephalitis, meningitis, or acute flaccid paralysis. This is the severe, potentially fatal form. It clusters almost entirely in the high-risk populations detailed below.

There is no approved antiviral treatment for WNV. No human vaccine exists. Prevention and early recognition are the only tools available.

Who Is at High Risk for Severe West Nile Virus Illness? The Complete, Updated List

The following risk groups are identified based on CDC surveillance data, the 2025 JAMA Network Open cohort study (Judson & Dowdy, analyzing 3,064 WNV patients from 2013–2024), and published clinical literature. These are not theoretical risks — they are statistically confirmed patterns.

1. Adults Over 60: The Single Biggest Risk Factor

Age is the most consistently documented risk factor for severe West Nile Virus illness. Adults aged 60 and older — and especially those over 65 — face a dramatically elevated risk of developing neuroinvasive disease compared to younger, healthy adults.

The AMA and CDC note that people 65 and older are five to twenty times more likely to develop WNV neuroinvasive disease than younger adults, with the risk approaching 2% compared to less than 0.5% in younger groups.

The biological explanation is immune senescence — the progressive decline of immune system function with age. Slowed T-cell responses, reduced antibody production, weakened innate immunity — the aging immune system simply cannot contain the virus before it reaches the brain. The JAMA Network Open study confirmed age per decade as an independent risk factor, even after controlling for all comorbidities.

• Adults 60+ are at elevated risk even without any other underlying conditions.
• Risk of fatal neuroinvasive disease rises sharply after age 70.
• WNV season (July–October) should be a period of heightened vigilance for all older adults and their caregivers.

2. Immunocompromised Individuals: Maximum Vulnerability

If there’s a single umbrella category carrying the most severe WNV risk, this is it. Anyone whose immune system is suppressed — from disease, medication, or treatment — faces significantly impaired ability to fight off the virus before it enters the nervous system.

Immunocompromising conditions with confirmed elevated WNV risk:

• HIV/AIDS — particularly with CD4 counts below 200 cells/μL
• Hematologic malignancies — leukemia, lymphoma, multiple myeloma (the JAMA 2025 study found hematologic malignancy carried an adjusted hazard ratio of 1.38 for neuroinvasive disease)
• Solid tumor cancers — especially during active chemotherapy
• Congenital immune deficiency disorders
• Bone marrow or stem cell transplant recipients

In immunocompromised patients, WNV can replicate with significantly less immune resistance. Published case series in Clinical Infectious Diseases have documented unusually prolonged, severe WNV illness in this population — in some cases lasting months. Some immunocompromised patients have been unable to clear the virus entirely.

3. Organ Transplant Recipients: Risk From Both Mosquitoes and the Transplant Itself

Solid organ transplant recipients — kidney, liver, heart, lung — represent a uniquely vulnerable group for two distinct reasons. First, the immunosuppressive medications required to prevent rejection create profound immune suppression. Second, West Nile Virus can be transmitted through the donated organ itself, not just through mosquito bites.

The CDC has documented multiple cases of donor-derived WNV transmission, where asymptomatic donors had undetected WNV viremia at the time of organ procurement. Blood supply screening for WNV has been standard practice since 2003, but organ donor screening remains a more complex challenge.

Anti-rejection medications — tacrolimus, cyclosporine, mycophenolate mofetil, prednisone — are themselves independent risk factors for severe WNV. The JAMA 2025 study specifically identified immune suppressant use (including tacrolimus and mycophenolate) as significantly associated with neuroinvasive disease in multivariable analysis.

Transplant recipients should be counseled about WNV risk year-round, not just during peak mosquito season. If you’ve received an organ in recent months, inform your transplant team immediately if you develop any febrile or neurological symptoms.

4. Blood Transfusion Recipients: A Non-Mosquito Route of Transmission

This group is frequently overlooked in public conversations about West Nile Virus — and it shouldn’t be. Blood transfusion is a documented, confirmed route of WNV transmission, separate from mosquito exposure entirely.

During periods of active WNV circulation, an infected donor may have undetected viremia — the virus is in the blood, but the donor hasn’t developed symptoms yet. If that blood is transfused to a recipient, WNV transfers directly. This risk prompted the United States to implement nationwide WNV nucleic acid testing (NAT) of blood donations in 2003, one of the largest blood safety expansions in American history.

Despite screening, the risk is not zero. Mini-pool NAT testing, used in most blood banks, can miss low-level viremia in a small percentage of donations. Individual donation testing offers greater sensitivity but isn’t universally used. The CDC is currently monitoring transfusion-related WNV clusters actively.

• Anyone who has received a blood transfusion during WNV season and subsequently develops fever, headache, or neurological symptoms should specifically mention the transfusion to their physician.
• Immunocompromised patients who receive transfusions face a compounded risk — both from their underlying immune suppression and from potential transfusion-acquired WNV.
• People receiving regular transfusions (e.g., for sickle cell disease or thalassemia) should discuss WNV risk awareness with their hematologist.

5. Diabetes Mellitus: An Underappreciated but Confirmed Risk Factor

Both Type 1 and Type 2 diabetes are associated with impaired immune defenses — reduced neutrophil function, complement system dysregulation, and weakened cellular immunity. These defects, combined with the chronic inflammatory state that accompanies poorly managed diabetes, make diabetics more susceptible to serious infections generally.

The JAMA Network Open 2025 cohort study confirmed diabetes as a significant risk factor for West Nile neuroinvasive disease in bivariate analysis across 3,064 WNV patients. Earlier research published in the American Journal of Tropical Medicine and Hygiene also identified diabetes as an independent risk factor for neuroinvasive WNV outcomes.

Glycemic control appears to matter. Diabetics with chronically elevated blood sugar show more pronounced immune dysfunction than those with well-managed HbA1c levels. This is one more reason why tight glucose control isn’t just about preventing nephropathy or retinopathy — it affects how your body handles viral threats.

• Both insulin-dependent and non-insulin-dependent diabetics should be aware of elevated WNV risk.
• Poorly controlled diabetes (HbA1c consistently above 8%) likely carries greater risk than well-managed diabetes.
• Diabetic patients who develop unexplained fever or neurological symptoms during WNV season should seek prompt evaluation.

6. Hypertension and Chronic Kidney Disease: Confirmed Risk in 2025 Data

These two conditions were both confirmed as independent risk factors for neuroinvasive WNV disease in the 2025 JAMA Network Open multivariable analysis — and both are highly prevalent in the United States adult population.

Chronic kidney disease (CKD), in particular, impairs immune function through mechanisms distinct from other immunodeficiencies: altered cytokine signaling, reduced lymphocyte proliferation, impaired phagocytosis. End-stage renal disease patients on dialysis face compounded risk — they receive frequent healthcare exposure, often require transfusions, and have chronically disrupted immune regulation.

Hypertension was also significantly associated with WNND in multivariable analysis (adjusted hazard ratio 1.18), suggesting that chronic vascular disease may play a role beyond simple immune suppression — possibly through impaired blood-brain barrier integrity or altered inflammatory responses.

If you have CKD or poorly controlled hypertension, add WNV awareness to your summer health planning. These conditions are common enough that a significant portion of neuroinvasive WNV cases in the U.S. involve patients who had “just” hypertension or kidney disease as their primary comorbidity.

7. Multiple Sclerosis: Newly Confirmed as a Major Risk Factor

This one surprised even specialists. The 2025 JAMA Network Open study found multiple sclerosis (MS) to be among the strongest independent risk factors for West Nile neuroinvasive disease — with an adjusted hazard ratio of 2.3, meaning MS patients were more than twice as likely to develop severe neurological WNV disease compared to individuals without MS.

Two mechanisms likely drive this risk. First, MS itself is associated with impaired immune regulation and disrupted central nervous system barriers. Second — and critically — most MS disease-modifying therapies (DMTs) are immunosuppressive by design. Natalizumab, ocrelizumab, siponimod, fingolimod, alemtuzumab — these medications meaningfully suppress immune responses, including the antiviral responses needed to contain WNV.

MS patients and their neurologists should discuss WNV risk proactively, especially for those on high-efficacy DMTs. During WNV season, any new neurological symptom in an MS patient deserves careful evaluation — WNV encephalitis can mimic MS relapse.

• MS patients on natalizumab, ocrelizumab, or other high-efficacy DMTs face compounded immune suppression.
• New neurological symptoms during summer in an MS patient should prompt WNV testing consideration.
• MS patients should follow mosquito prevention guidelines as strictly as transplant recipients and other immunocompromised individuals.

8. Cerebrovascular Disease and Prior Stroke: Increased Neurological Vulnerability

Individuals with a history of stroke, TIA (transient ischemic attack), or other cerebrovascular disease have pre-existing neurological vulnerability that appears to amplify the severity of WNV neuroinvasive disease. The 2025 JAMA study confirmed cerebrovascular disease as an independent risk factor for both WNND and WNV-related mortality.

The likely mechanism involves impaired cerebrovascular integrity — the blood-brain barrier in people with cerebrovascular disease may be more permeable or more susceptible to inflammatory damage, allowing the virus to cross into brain tissue more readily and cause greater inflammation once there.

For patients who have had a stroke or are being managed for cerebrovascular disease, this isn’t just a theoretical concern. West Nile encephalitis in someone with pre-existing brain injury can produce disproportionately severe cognitive and functional outcomes.

9. Alcohol-Related Disorders: A Significant and Often Overlooked Risk

Chronic heavy alcohol use produces a well-documented state of immune dysregulation — sometimes called alcoholic immune deficiency. It impairs neutrophil function, disrupts mucosal immune barriers, reduces T and B lymphocyte responses, and promotes systemic inflammation that paradoxically weakens pathogen-specific immunity.

The 2025 JAMA Network Open study found alcohol-related disorders to be one of the strongest independent risk factors for West Nile neuroinvasive disease, with an adjusted hazard ratio of 1.54 — higher than hypertension and CKD in the same analysis. This is a statistically significant finding from a large national cohort and should change how clinicians counsel patients with alcohol use disorders during WNV season.

Alcohol-related liver disease adds another dimension: impaired hepatic immune function, reduced complement production, and portal hypertension all contribute to systemic immune compromise.

10. People with Chronic Liver Disease or Hepatitis: Impaired Frontline Immune Defense

The liver does far more than process toxins — it houses a substantial portion of the body’s innate immune system. Kupffer cells, the liver’s resident macrophages, are critical early responders to bloodborne viral pathogens, including flaviviruses like West Nile Virus.

When liver function is compromised — through chronic hepatitis B or C, alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), or cirrhosis — this first-line immune surveillance is significantly weakened.

Patients with autoimmune hepatitis are often on corticosteroids or azathioprine, adding medication-induced immune suppression on top of already impaired hepatic immunity. Cirrhotic patients additionally suffer from reduced complement protein synthesis, further reducing their ability to neutralize viral pathogens in the bloodstream.

If you have chronic liver disease of any etiology, discuss WNV risk with your hepatologist or gastroenterologist — particularly during peak mosquito season.

11. Pregnancy: The Risk Is to the Fetus, Not Just the Mother

Pregnancy creates a unique immunological state — the immune system modulates itself to tolerate the fetus, which can leave the mother more vulnerable to certain infections. But the greater concern with WNV during pregnancy isn’t the mother’s own illness. It’s vertical transmission to the fetus.

Case reports published in peer-reviewed literature have documented intrauterine WNV transmission, with chorioamnionitis and fetal brain lesions in some cases. The CDC acknowledges that WNV can also be transmitted through breast milk, though the risk is considered low and breastfeeding benefits are generally judged to outweigh it.

Pregnant women should be especially diligent about mosquito bite prevention. DEET-based repellents are considered safe during pregnancy per CDC and EPA guidance. Any fever or neurological symptom during pregnancy in WNV season warrants prompt OB/GYN consultation.

12. Male Sex: A Biological Risk Factor, Not Just Demographics

This isn’t widely discussed — but the 2025 JAMA Network Open study, analyzing over 3,000 WNV patients, found male sex to be a statistically significant independent risk factor for neuroinvasive disease, with an adjusted hazard ratio of 1.29. Men were 29% more likely than women to develop severe neurological WNV illness even after adjusting for all other risk factors.

The reason isn’t fully understood. Hypotheses include sex-based differences in immune responses — specifically, women tend to mount stronger innate and adaptive immune responses than men, which may offer greater protection against viral neuroinvasion. Hormonal differences (estrogen’s immunomodulatory effects) and differences in healthcare-seeking behavior may also play roles.

This doesn’t mean healthy young men should panic about West Nile. But when combined with other risk factors — age, diabetes, hypertension — male sex adds to the cumulative risk picture and is worth factoring into clinical assessments.

13. Immune-Suppressing Medications: Risk Independent of Underlying Condition

Several medication classes suppress immune function as either their primary mechanism or a documented side effect — raising WNV risk in patients who take them, independently of whatever condition the drug is treating.

• Corticosteroids (prednisone, dexamethasone) — especially at doses above 20mg/day or with prolonged use exceeding two weeks
• Biologic agents — TNF inhibitors (adalimumab, etanercept, infliximab), rituximab, natalizumab, ocrelizumab, alemtuzumab
• JAK inhibitors — tofacitinib, baricitinib, upadacitinib (increasingly common for RA and IBD)
• DMARDs — methotrexate, leflunomide, azathioprine
• Calcineurin inhibitors post-transplant — tacrolimus (confirmed in JAMA 2025), cyclosporine
• Mycophenolate mofetil (MMF) — confirmed as significant in JAMA 2025 multivariable analysis
• Chemotherapy agents — cyclophosphamide, and regimens causing bone marrow suppression

If you are on any of these medications, discuss WNV risk with your prescribing physician before summer. In most cases, stopping the medication isn’t the answer — but understanding your elevated risk absolutely is.

14. COPD and Other Chronic Pulmonary Conditions

Chronic obstructive pulmonary disease (COPD) was identified as a risk factor for WNV neuroinvasive disease in bivariate analysis in the 2025 JAMA study. COPD is associated with chronic systemic inflammation, impaired mucociliary clearance, and in many patients, ongoing corticosteroid use — all of which may contribute to impaired antiviral immune responses.

COPD patients, many of whom are older adults with additional comorbidities, often sit at the intersection of multiple WNV risk factors. Awareness within this population — and their pulmonologists — warrants attention.

What Severe West Nile Neuroinvasive Disease Actually Looks Like

Knowing the presentations matters — because WNV encephalitis is often initially mistaken for bacterial meningitis, a stroke, or a psychiatric episode. West Nile neuroinvasive disease takes three forms:

• West Nile encephalitis — inflammation of the brain itself. Confusion, altered consciousness, tremors, seizures, coma. This is the most dangerous and most frequently fatal presentation.
• West Nile meningitis — inflammation of the meningeal membranes. Severe headache, stiff neck, high fever, photophobia. Generally a better prognosis than encephalitis but still serious.
• West Nile poliomyelitis (acute flaccid paralysis) — sudden, asymmetric limb weakness mimicking polio. Can involve respiratory muscles. Paralysis can be permanent.

There is no approved antiviral treatment for West Nile Virus. Care is supportive — IV fluids, mechanical ventilation if needed, seizure management, intensive nursing. This is why prevention is not optional for high-risk individuals. It is everything.

Warning Signs: West Nile Virus Symptoms That Demand Immediate Attention

High-risk individuals who develop any of the following symptoms during WNV season — particularly after possible mosquito exposure, a recent blood transfusion, or organ transplant — should seek emergency evaluation without delay:

• High fever, usually above 102–103°F, that comes on relatively suddenly
• Severe, unusual headache — not like a typical headache
• Stiff neck with difficulty touching chin to chest
• Confusion, disorientation, or sudden personality changes
• Sudden limb weakness or paralysis, especially asymmetric
• Tremors, muscle twitching, or jerky involuntary movements
• Sensitivity to light (photophobia) or double vision
• Seizures in someone with no prior seizure history
• Decreasing level of consciousness

Tell the emergency team explicitly: “I may have had mosquito exposure recently” or “I received a blood transfusion X weeks ago.” WNV is diagnosed through IgM antibody testing on blood or cerebrospinal fluid (CSF), available at most state public health laboratories and many commercial labs.

How to Reduce West Nile Virus Risk: What Actually Works

Because no vaccine or treatment exists, prevention carries the full weight of protection. Here is what is actually evidence-supported:

1. Use EPA-Registered Mosquito Repellents Correctly

The following active ingredients are EPA-registered and proven effective:

• DEET (20–30%) — the most studied repellent; safe for pregnant women and children over 2 months; reapply as directed
• Picaridin — comparable effectiveness to DEET, lighter texture, no odor
• IR3535 — effective and gentle; widely used in Europe
• Oil of lemon eucalyptus (OLE) — plant-based, effective; NOT for children under age 3

Apply repellent to all exposed skin. For immunocompromised and other high-risk individuals, using repellent every time you go outdoors during WNV season is not excessive — it is appropriate.

2. Avoid Peak Mosquito Hours and Cover Up

Culex mosquitoes — the primary WNV vector — bite most aggressively at dusk and dawn. Stay indoors or use repellent during these windows. Wear long-sleeved shirts and long pants treated with permethrin, a clothing-applied insecticide proven to repel and kill mosquitoes on contact. Permethrin-treated clothing remains effective through multiple washes.

3. Eliminate Standing Water Around Your Property

A single flower pot, clogged gutter, or neglected birdbath can produce hundreds of Culex mosquitoes. Tip out standing water weekly. Treat ornamental ponds or water features with BTI (Bacillus thuringiensis israelensis) mosquito dunks — a biological larvicide safe for fish and wildlife. This is the highest-impact community-level WNV prevention measure that every household can implement.

4. Secure Your Home

Use intact window and door screens — repair or replace any with holes or tears. Use air conditioning during peak hours when possible. If you sleep with windows open, use bed nets. High-risk individuals should treat these as non-negotiable summer habits rather than optional precautions.

All High-Risk Groups at a Glance: Quick Reference Table

The following groups face elevated risk for severe or fatal West Nile Virus disease based on current evidence:

Conclusion: If You’re at High Risk, Prevention Is Not Optional

West Nile Virus is not equally dangerous to everyone — but for those at high risk for severe West Nile Virus illness, the danger is real, documented, and growing. The risk pool is broader than most people realize: it includes not just the elderly and immunocompromised, but blood transfusion recipients, people with multiple sclerosis, those with cerebrovascular disease, alcohol-related disorders, hypertension, COPD, and males across every age group.

The 2025 JAMA Network Open study — analyzing over 3,000 real-world WNV cases — has sharpened our picture of exactly who is vulnerable. The findings should change how clinicians counsel at-risk patients, and how those patients approach each mosquito season.

No antiviral. No vaccine. Prevention and early recognition are the only defenses. Apply repellent. Eliminate standing water. Know your risk factors. And if you’re in a high-risk category — have that conversation with your physician before the mosquitoes return.

Are you or a loved one in one of the high-risk groups listed above? Have you had a WNV-related experience you’d like to share? Leave a comment below — your story might help another reader recognize their own risk in time.

Frequently Asked Questions (FAQs)

References and Authoritative Sources

1. Judson SD, Dowdy D. Risk Factors for West Nile Neuroinvasive Disease and Mortality in the US, 2013–2024. JAMA Network Open. 2025.
2. Centers for Disease Control and Prevention. West Nile Virus. https://www.cdc.gov/west-nile-virus/
3. American Medical Association. West Nile Virus Deaths Up 32% in 2025. AMA-CDC Webinar Summary. December 2025.
4. CDC MMWR. West Nile Virus and Other Nationally Notifiable Arboviral Diseases — United States, 2023. MMWR Morb Mortal Wkly Rep. 2025;74.
5. Davis LE et al. West Nile virus neuroinvasive disease. Annals of Neurology. 2006.
6. Susan L. Stramer et al. West Nile Virus among Blood Donors in the United States, 2003 and 2004. NEJM. 2003.
7. Nash D et al. The outbreak of West Nile virus infection in the New York City area in 1999. NEJM. 2001.
8. U.S. EPA. Repellents: Protection Against Mosquitoes, Ticks, and Other Arthropods.
9. Klee AL et al. Long-term prognosis for clinical West Nile virus infection. Emerging Infectious Diseases. 2004.