Prompt Reduction in CRP, IL-6, IFN-gamma, IP-10, and MCP-1 and a Relatively Low Basal Ratio of Ferritin/CRP Is Possibly Associated With the Efficacy of Tocilizumab Monotherapy in Severely to Critically Ill Patients With COVID-19


Posted: 2021-10-11 19:00:00
Front Med (Lausanne) . 2021 Sep 23;8:734838. doi: 10.3389/fmed.2021.734838. eCollection 2021. Shoji Hashimoto 1 , Kazuyuki Yoshizaki 2 , Kazuko Uno 3 , Heita Kitajima 1 , Tsuyoshi Arai 1 , Yoshitaka Tamura 1 , Hiroshi Morishita 1 , Hiroto Matsuoka 1 , Yuki Han 1 , Seijiro Minamoto 1 , Tomonori Hirashima 1 , Tomoki Yamada 1 , Yozo Kashiwa 1 , Makoto Kameda 1 , Seiji Yamaguchi 1 , Yasunari Tsuchihashi 3 , Mitsuhiro Iwahashi 4 , Emi Nakayama 5 , Tatsuo Shioda 5 , Takayuki Nagai 1 , Toshio Tanaka 1 Affiliations Expand Affiliations 1 Osaka Prefectural Hospital Organization Osaka Habikino Medical Center, Osaka, Japan. 2 Department of Organic Fine Chemicals, Institute of Scientific and Industry Research, Osaka University, Osaka, Japan. 3 Division of Basic Research, Louis Pasteur Center for Medical Research, Kyoto, Japan. 4 Higashi Hiroshima Memorial Hospital, Hiroshima, Japan. 5 Department of Viral Infection, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. Item in Clipboard Shoji Hashimoto et al. Front Med (Lausanne). 2021. Show details Display options Display options Format Front Med (Lausanne) . 2021 Sep 23;8:734838. doi: 10.3389/fmed.2021.734838. eCollection 2021. Authors Shoji Hashimoto 1 , Kazuyuki Yoshizaki 2 , Kazuko Uno 3 , Heita Kitajima 1 , Tsuyoshi Arai 1 , Yoshitaka Tamura 1 , Hiroshi Morishita 1 , Hiroto Matsuoka 1 , Yuki Han 1 , Seijiro Minamoto 1 , Tomonori Hirashima 1 , Tomoki Yamada 1 , Yozo Kashiwa 1 , Makoto Kameda 1 , Seiji Yamaguchi 1 , Yasunari Tsuchihashi 3 , Mitsuhiro Iwahashi 4 , Emi Nakayama 5 , Tatsuo Shioda 5 , Takayuki Nagai 1 , Toshio Tanaka 1 Affiliations 1 Osaka Prefectural Hospital Organization Osaka Habikino Medical Center, Osaka, Japan. 2 Department of Organic Fine Chemicals, Institute of Scientific and Industry Research, Osaka University, Osaka, Japan. 3 Division of Basic Research, Louis Pasteur Center for Medical Research, Kyoto, Japan. 4 Higashi Hiroshima Memorial Hospital, Hiroshima, Japan. 5 Department of Viral Infection, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. Item in Clipboard CiteDisplay options Display options Format Abstract Background and Aim: Tocilizumab, a humanized anti-IL-6 receptor antibody, has been used to treat severely to critically ill patients with COVID-19. A living systematic review with meta-analysis of recent RCTs indicates that the combination therapy of corticosteroids and tocilizumab produce better outcomes, while previous observational studies suggest that tocilizumab monotherapy is beneficial for substantial numbers of patients. However, what patients could respond to tocilizumab monotherapy remained unknown. Methods: In this retrospective study we evaluated the effects of tocilizumab monotherapy on the clinical characteristics, serum biomediator levels, viral elimination, and specific IgG antibody induction in 13 severely to critically ill patients and compared with those of dexamethasone monotherapy and dexamethasone plus tocilizumab. Results: A single tocilizumab administration led to a rapid improvement in clinical characteristics, inflammatory findings, and oxygen supply in 7 of 11 patients with severe COVID-19, and could recover from mechanical ventilation management (MVM) in 2 patients with critically ill COVID-19. Four patients exhibited rapidly worsening even after tocilizumab administration and required MVM and additional methylprednisolone treatment. Tocilizumab did not delay viral elimination or inhibit IgG production specific for the virus, whereas dexamethasone inhibited IgG induction. A multiplex cytokine array system revealed a significant increase in the serum expression of 54 out of 80 biomediators in patients with COVID-19 compared with that in healthy controls. Compared with those who promptly recovered in response to tocilizumab, patients requiring MVM showed a significantly higher ratio of basal level of ferritin/CRP and a persistent increase in the levels of CRP and specific cytokines and chemokines including IL-6, IFN-γ, IP-10, and MCP-1. The basal high ratio of ferritin/CRP was also associated with clinical deterioration even in patients treated with dexamethasone and tocilizumab. Conclusion: Tocilizumab as monotherapy has substantial beneficial effects in some patients with severe COVID-19, who showed a relatively low level of the ratio of ferritin/CRP and prompt reduction in CRP, IL-6, IFN-γ, IP-10, and MCP-1. The high ratio of ferritin/CRP is associated with rapid worsening of pneumonia. Further evaluation is warranted to clarify whether tocilizumab monotherapy or its combination with corticosteroid is preferred for severely to critically ill patients with COVID-19. Keywords: COVID-19; IL-6; cytokine storm; dexamethasone; tocilizumab. Copyright © 2021 Hashimoto, Yoshizaki, Uno, Kitajima, Arai, Tamura, Morishita, Matsuoka, Han, Minamoto, Hirashima, Yamada, Kashiwa, Kameda, Yamaguchi, Tsuchihashi, Iwahashi, Nakayama, Shioda, Nagai and Tanaka. Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

参考サイト PubMed: covid-19



バイオクイックニュース日本語版:COVID-19特集

バイオクイックニュース日本語版
10月 14, 2020 バイオアソシエイツ

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男性特有のY染色体遺伝子のあまり知られていない役割に新たな光が当てられ、 COVID-19 を含むさまざまな病気で、男性が女性とは異なる重症化を示すのか理由を説明することができるかもしれない。この研究成果は、モントリオール大学・モントリオール臨床研究所の実験的心臓血管生物学研究ユニットのディレクターであるChristian Deschepper医学博士によって、Scientific Reports…

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