Frequent Illness: Which Labs to Check When You're Always Getting Sick

Overview.

Most healthy adults get 2-4 upper respiratory infections per year. When infections are more frequent, more severe, or unusually prolonged, it warrants investigation. Common causes include nutritional deficiencies (vitamin D, zinc, iron), undiagnosed diabetes, chronic stress, sleep deprivation, and medication effects. Rarely, recurrent infections indicate primary immunodeficiency — a group of conditions affecting immunoglobulin production or immune cell function that affect ~1 in 1,200 people.

Frequent illness ranges from increased susceptibility to common viral infections (colds, flu) to recurrent bacterial infections requiring repeated antibiotics (sinusitis, pneumonia, UTIs). The clinical concern increases with infection severity, need for IV antibiotics, unusual organisms, or family history of immunodeficiency.

Prevalence: Most adults have 2-4 URIs per year. Children have 6-8 (normal). Adults with >6 infections per year, >2 bacterial sinusitis or pneumonias per year, or infections requiring >2 courses of antibiotics warrant immune evaluation. Primary immunodeficiency affects ~1 in 1,200 people (most undiagnosed).

What to test.

First-line tests

• CBC with Differential — Identifies neutropenia (low neutrophils — bacterial infection risk), lymphopenia (low lymphocytes — viral/opportunistic infection risk), and overall immune cell counts. Most important single test for immune evaluation.
• Vitamin D (25-OH) — Vitamin D is a critical immune modulator. Deficiency (<20 ng/mL) is associated with increased respiratory infection frequency and severity. Multiple RCTs show supplementation reduces infection risk, especially in deficient individuals.
• Ferritin — Iron is essential for immune cell proliferation and function. Iron deficiency impairs T-cell and neutrophil function. Also: iron overload (high ferritin) paradoxically increases infection susceptibility by feeding pathogens.
• Fasting Glucose / HbA1c — Undiagnosed diabetes is one of the most common causes of recurrent infections — hyperglycaemia impairs neutrophil function, complement activity, and wound healing. UTIs, candidiasis, and skin infections are classic.

Second-line tests

• Immunoglobulins (IgG, IgA, IgM) — Screens for antibody deficiency — the most common primary immunodeficiency. Low IgG causes recurrent sinopulmonary infections. IgA deficiency (1 in 400 people) often presents with GI and respiratory infections. Low IgG subclasses may be missed by total IgG.
• Zinc — Zinc is essential for T-cell maturation, NK cell activity, and neutrophil function. Deficiency is common in elderly, vegetarians, alcoholics, and malabsorption conditions. Supplementation in deficiency reduces infection duration and severity.
• Albumin / Total Protein — Protein malnutrition impairs antibody production and immune cell function. Low albumin in the context of recurrent infections suggests underlying malnutrition, liver disease, or protein-losing conditions.
• TSH — Both hypo- and hyperthyroidism affect immune function. Hypothyroidism impairs innate immunity. Screen as part of general evaluation since thyroid disease is common and easily missed.

Specialized tests

• HIV Test — HIV causes progressive immunodeficiency. Should be offered in any adult with unexplained recurrent infections, especially opportunistic infections, lymphopenia, or unintentional weight loss. Testing is routine and confidential.
• Complement Levels (C3, C4, CH50) — Complement deficiency causes recurrent encapsulated bacterial infections (pneumococcus, meningococcus, Haemophilus). Consider if recurrent meningitis or invasive bacterial infections.

Common causes.

• Vitamin D Deficiency — Increased frequency and duration of upper respiratory infections, slow recovery
• Undiagnosed Diabetes — Recurrent UTIs, candidiasis, skin infections, slow wound healing

Diagnostic patterns.

• Low total IgG + recurrent sinopulmonary infections — likely Common variable immunodeficiency (CVID) or IgG subclass deficiency. Next step: Immunology referral; vaccine response testing; possible immunoglobulin replacement
• Low vitamin D + frequent URIs + winter predominance — likely Vitamin D deficiency-related immune impairment. Next step: Vitamin D supplementation (2,000-4,000 IU/day); recheck in 3 months
• Elevated HbA1c + recurrent candidiasis + UTIs — likely Undiagnosed or poorly controlled diabetes. Next step: Diabetes management; HbA1c target <7%; infections resolve with glucose control
• Normal labs + high stress + poor sleep + frequent colds — likely Stress/lifestyle-related immune suppression. Next step: Sleep hygiene (7-9 hours), stress management, regular exercise, nutrition optimisation

Lifestyle.

Non-medical causes

• Chronic sleep deprivation (<6 hours/night — increases infection risk 4x)
• Chronic psychological stress (suppresses cellular immunity)
• Sedentary lifestyle (moderate exercise boosts immune surveillance)
• Smoking (impairs mucosal and systemic immunity)
• Excessive alcohol (>14 units/week impairs neutrophil function)
• Overtraining in athletes (immunosuppression from excessive exercise)
• Medications: corticosteroids, immunosuppressants, proton pump inhibitors (increase pneumonia risk)

Considerations

• Sleep: 7-9 hours/night — single most impactful immune intervention
• Regular moderate exercise (150 min/week) enhances immune surveillance
• Balanced nutrition: adequate protein, zinc, vitamin D, vitamin C
• Stress management: chronic stress measurably suppresses immune function
• Hand hygiene: most effective prevention of respiratory and GI infections
• Vaccination: ensure influenza (annual), pneumococcal (if indicated), COVID-19 are up to date

FAQs.

Red flags.