Association of prior lymphopenia with mortality in pneumonia: a cohort study in UK primary care

BACKGROUND: Lymphopenia (reduced lymphocyte count) during infections, such as pneumonia, is common and is associated with increased mortality. Little is known about the relationship between lymphocyte count before developing infections and mortality risk. AIM: To identify whether patients with lymphopenia who develop pneumonia have increased risk of death. DESIGN AND SETTING: A cohort study set in the Clinical Practice Research Datalink (CPRD) linked to national death records, in primary care. This database is representative of the UK population and is extracted from routine records. METHOD: Patients aged >50 years with a pneumonia diagnosis were included from January 1998 until January 2019. The relationship between lymphocyte count and mortality was measured, using a time-to-event (multivariable Cox regression) approach, adjusted for age, sex, social factors, and potential causes of lymphopenia. The primary analysis used the most recent test before pneumonia. The primary outcome was 28-day, all-cause mortality. RESULTS: A total of 40 909 participants with pneumonia were included, with 28 556 having had a lymphocyte count test before pneumonia (median time between test and diagnosis was 677 days). When lymphocyte count was categorised (0–1 × 10(9) cells/L, 1–2 × 10(9) cells/L, 2–3 × 10(9) cells/L, >3 × 10(9) cells/L, never tested), both 28-day and 1-year mortality varied significantly: 14%, 9.2%, 6.5%, 6.1%, and 25%, respectively, for 28-day mortality, and 41%, 29%, 22%, 20%, and 52% for 1-year mortality. In multivariable Cox regression, lower lymphocyte count was consistently associated with increased hazard of death. CONCLUSION: Lymphopenia is an independent predictor of mortality in primary care pneumonia. Even low–normal lymphopenia (1–2 × 10(9) cells/L) is associated with an increase in short- and long-term mortality compared with higher counts.