Analysis of Early Biomarkers Associated with the Development of Critical Respiratory Failure in Coronavirus Disease 2019 (COVID-19)
Hiroyoshi Yamada,
Masaki Okamoto,
Yoji Nagasaki,
Suzuyo Yoshio,
Takashi Nouno,
Chiyo Yano,
Tomohiro Tanaka,
Fumi Watanabe,
Natsuko Shibata,
Yoko Arimizu,
Yukako Fukamachi,
Yoshiaki Zaizen,
Naoki Hamada,
Atsushi Kawaguchi,
Tomoaki Hoshino,
Shigeki Morita
Affiliations
Hiroyoshi Yamada
Department of Respirology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
Masaki Okamoto
Department of Respirology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
Yoji Nagasaki
Department of Infectious Disease, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
Suzuyo Yoshio
Shino-Test Corporation, 3-7-9 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8410, Japan
Takashi Nouno
Department of Respirology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
Chiyo Yano
Department of Respirology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
Tomohiro Tanaka
Department of Respirology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
Fumi Watanabe
Department of Respirology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
Natsuko Shibata
Department of Respirology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
Yoko Arimizu
Department of Infectious Disease, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
Yukako Fukamachi
Department of Infectious Disease, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
Yoshiaki Zaizen
Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Fukuoka 830-0011, Japan
Naoki Hamada
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1 Maidashi Higashi-ku, Fukuoka 812-0054, Japan
Atsushi Kawaguchi
Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan
Tomoaki Hoshino
Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Fukuoka 830-0011, Japan
Shigeki Morita
Department of Cardiovascular Surgery, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
Certain biomarkers predict death due to acute respiratory distress syndrome in COVID-19 patients. We retrospectively analyzed biomarkers associated with time to mechanical ventilation for respiratory failure due to COVID-19 (time-to-mechanical ventilation) in 135 consecutive patients in our hospital. We analyzed biomarkers that were elevated immediately (at admission) and later (3 days after admission) using Cox proportional hazards regression analysis. Independent biomarkers of time-to-mechanical ventilation were high C-reactive protein (CRP), interleukin (IL)-6, and Krebs von den Lungen-6 (KL-6) concentrations at admission and elevated CRP, high-mobility group box-1 protein (HMGB-1), and d-dimer levels and low platelets 3 days after admission. Receiver operating characteristic analysis for detecting the association between independent biomarkers associated with time-to-event in multivariate analyses and the start of mechanical ventilation revealed that these biomarkers had area under the curve values higher than 0.700. The present study suggests that CRP was the only biomarker associated with time-to-mechanical ventilation both at admission and 3 days after admission. Moreover, IL-6 (an inflammatory cytokine), HMGB-1 (a late inflammatory mediator), and KL-6 (reflecting injury and/or remodeling of type II pneumocytes) were associated with outcomes in COVID-19 as reported previously. In conclusion, increased CRP, IL-6, KL-6, HMGB-1, and d-dimer levels and decreased platelet counts were associated with the start of mechanical ventilation due to COVID-19.
