| Contributors: |
Cidade, J; Taccone, F; Reyes, L; Merson, L; Lefevre, B; Citarella, B; Fatoni, A; Povoa, P; Zucman, D; Zoufaly, A; Zayyad, H; Zaynah, N; Zawadka, K; Zanella, A; Zambrano, M; Zambon, M; Zaidan, N; Zahid, M; Zabbe, M; Zaaqoq, A; Yuliarto, S; Yousif, O; Yonis, H; Yiaye, T; Yeoh, C; Yelnik, C; Abdelaal, A; Hing, N; Yazdanpanah, Y; Yarad, E; Yamazaki, M; Yakop, S; Xynogalas, I; Xian, L; Wong, C; Wong, T; Wong, Y; Wong, X; Wittman, J; Witt, K; Wils, E; Williams, B; Williams, P; Williams, V; Wijaya, S; Wiedemann, A; White, N; Whelan, B; Wham, M; Wesselius, S; Wen, T; Webb, S; Walsh, L; Wainstein, M; Wahid, N; Wahab, N; Wahab, S; Vuotto, F; Vongsouvath, M; Villoldo, A; Villar, J; Vijayan, D; Vieira, C; Verbon, A; Ventura, S; Veislinger, A; Veeran, S; Vauchy, C; Vasudayan, S; Varrone, M; Vanel, N; Van Willigen, H; Van Twillert, G; Van Someren Greve, F; Van Netten, C; Van Hattem, J; Van Gulik, L; Van Gorp, E; Van Der Werf, S; Van Der Voort, P; Van Der Feltz, M; Van Den Berge, M; Val-Flores, L; Vajdovics, C; Uyeki, T; Usman, A; Uribe, A; Ullrich, R; Udy, A; Udayanga, P; Uchiyama, M; Twardowski, P; Tveita, A; Turtle, L; Turgeon, A; Tuite, H; Tubiana, S; Tual, C; Truong, J; Trontzas, I |
| Description: |
Objective: Immune dysregulation plays a pivotal role in the pathophysiology of sepsis and COVID-19, with lymphopenia emerging as a consistent marker of severity and poor prognosis. However, most existing studies have assessed lymphocyte counts at isolated time points, limiting insights into their temporal behavior and prognostic value. The dynamics of lymphocyte recovery or persistence of lymphopenia remain largely unexplored in large populations, as well as the impact of adjunctive therapies such as corticosteroids. We hypothesized that the persistence or recovery of lymphopenia may be key to understanding disease progression and predicting outcomes. Using the multinational ISARIC cohort, we investigated longitudinal lymphocyte trajectories in hospitalized patients and the clinical determinants associated with their evolution over time. Methods: We conducted a multinational prospective observational cohort study using data from the ISARIC-WHO Clinical Characterization Protocol. Patients with confirmed SARS-CoV-2 infection and at least four lymphocyte measurements during the first 28 days of hospitalization were included. We analyzed lymphocyte trajectories, Cox regression survival analyses and multivariable linear regression modelling. We also applied multistate models and joint modeling to assess the association between lymphocyte trajectories and 28-day mortality, incorporating corticosteroid use as a time-varying covariate. Results: Of 945,317 screened patients, 231,933 hospitalized adults with confirmed COVID-19 and sufficient lymphocyte data were included, with 56.6% classified as lymphopenic. Lymphopenia was independently associated with higher rates of ICU admission, organ support, and in-hospital mortality (OR = 1.52, 95% CI 1.48–1.55), and lower absolute lymphocyte counts were strongly linked to worse survival in adjusted Cox models (HR = 1.33 per 1 × 109 cells/L decrease, 95% CI 1.28–1.38). Multistate modeling revealed that lymphopenic patients had a significantly higher daily transition rate to death ... |