Use and misuse of biomarkers and the role of D-dimer and C-reactive protein in the management of COVID-19: A post-hoc analysis of a prospective cohort study

Fabio Augusto Rodrigues Gonçalves, Bruno Adler Maccagnan Pinheiro Besen, Clarice Antunes de Lima, Aline Pivetta Corá, Antônio José Rodrigues Pereira, Sandro Félix Perazzio, Christiane Pereira Gouvea, Luiz Augusto Marcondes Fonseca, Evelinda Marramon Trindade, Nairo Massakazu Sumita, Alberto José da Silva Duarte, Arnaldo Lichtenstein, HCFMUSP COVID-19 Study Group, Eloisa Bonfa, Edivaldo M. Utiyama, Aluisio C. Segurado, Beatriz Perondi, Anna Miethke-Morais, Amanda C. Montal, Leila Harima, Solange R.G. Fusco, Marjorie F. Silva, Marcelo C. Rocha, Izabel Marcilio, Izabel Cristina Rios, Fabiane Yumi Ogihara Kawano, Maria Amélia de Jesus, Ésper George Kallas, Carolina Carmo, Clarice Tanaka, Heraldo Possolo de Souza, Julio F.M. Marchini, Carlos Carvalho, Juliana C. Ferreira, Anna Sara Shafferman Levin, Maura Salaroli Oliveira, Thaís Guimarães, Carolina dos Santos Lázari, Ester Sabino, Marcello M.C. Magri, Tarcisio E.P. Barros-Filho, Maria Cristina Peres Braido Francisco, Silvia F. Costa

Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and these complications can lead to a poorer prognosis. This study aimed to evaluate the association and temporal trends of D-dimer and C-reactive protein (CRP) levels with the incidence of venous thromboembolism (VTE), hospital mortality, and costs among inpatients with COVID-19. Data were extracted from electronic patient records and laboratory databases. Crude and adjusted associations for age, sex, number of comorbidities, Sequential Organ Failure Assessment score at admission, and D-dimer or CRP logistic regression models were used to evaluate associations. Between March and June 2020, COVID-19 was documented in 3,254 inpatients. The D-dimer level ≥4,000 ng/mL fibrinogen equivalent unit (FEU) mortality odds ratio (OR) was 4.48 (adjusted OR: 1.97). The CRP level ≥220 mg/dL OR for death was 7.73 (adjusted OR: 3.93). The D-dimer level ≥4,000 ng/mL FEU VTE OR was 3.96 (adjusted OR: 3.26). The CRP level ≥220 mg/dL OR for VTE was 2.71 (adjusted OR: 1.92). All these analyses were statistically significant (p<0.001). Stratified hospital costs demonstrated a dose-response pattern. Adjusted D-dimer and CRP levels were associated with higher mortality and doubled hospital costs. In the first week, elevated D-dimer levels predicted VTE occurrence and systemic inflammatory harm, while CRP was a hospital mortality predictor. D-dimer and CRP levels were associated with higher hospital mortality and a higher incidence of VTE. D-dimer was more strongly associated with VTE, although its discriminative ability was poor, while CRP was a stronger predictor of hospital mortality. Their use outside the usual indications should not be modified and should be discouraged.