tetano
Editor, Senior Moderator
Ther Adv Infect Dis
. 2026 Mar 15:13:20499361261431488.
doi: 10.1177/20499361261431488. eCollection 2026 Jan-Dec.
Symptom relief and cytokine modulation by clarithromycin in mild COVID-19 pneumonia: an exploratory, multicenter, randomized-controlled open-label trial (CAME-COVID study)
Kazuko Yamamoto[SUP] 1 2 [/SUP], Naoki Iwanaga[SUP] 1 [/SUP], Asuka Umemura[SUP] 3 [/SUP], Toyomitsu Sawai[SUP] 4 [/SUP], Makoto Sumiyoshi[SUP] 5 [/SUP], Kohji Hashiguchi[SUP] 6 [/SUP], Yusuke Mori[SUP] 7 [/SUP], Hiroshi Ishii[SUP] 8 [/SUP], Yoji Futsuki[SUP] 9 [/SUP], Maiko Kiyohara[SUP] 1 [/SUP], Kenji Ota[SUP] 10 [/SUP], Kosuke Kosai[SUP] 10 [/SUP], Daisuke Sasaki[SUP] 10 [/SUP], Yuki Takamatsu[SUP] 11 [/SUP], Shingo Inoue[SUP] 11 [/SUP], Kouichi Morita[SUP] 11 [/SUP], Shin Tsutsui[SUP] 12 [/SUP], Kazuto Ashizawa[SUP] 13 [/SUP], Takahiro Takazono[SUP] 1 [/SUP], Noriho Sakamoto[SUP] 1 [/SUP], Naoki Hosogaya[SUP] 1 [/SUP], Masato Tashiro[SUP] 14 15 [/SUP], Takeshi Tanaka[SUP] 14 [/SUP], Koichi Izumikawa[SUP] 15 [/SUP], Katsunori Yanagihara[SUP] 10 [/SUP], Hiroshi Mukae[SUP] 1 [/SUP]
Affiliations
Background: Coronavirus disease 2019 (COVID-19) remains an epidemic worldwide, and long COVID is a major social concern. Therapeutic options for relieving symptoms of COVID-19 pneumonia are limited. Clarithromycin (CAM), a macrolide antimicrobial, also functions as an immunomodulator.
Objectives: To assess the efficacy of CAM in improving clinical symptoms and attenuating inflammation in patients with mild COVID-19, with the aim of preventing progression to severe disease.
Design: An exploratory, multicenter, randomized-controlled, open-label trial.
Methods: This trial enrolled patients with mild COVID-19 pneumonia without oxygen supplementation from May 2021 through February 2022 in eight hospitals in Japan. Patients were randomly assigned in a 1:1:1 ratio to groups A (CAM 800 mg/day, 7 days), B (CAM 400 mg/day, 7 days), or C (standard treatment). The primary endpoint was the number of days required for 50% improvement in seven symptoms (fatigue, headache, cough, shortness of breath, taste/smell disturbance, and general unwellness) based on severity scores. Secondary endpoints included inflammatory cytokines, viral load, immunoglobulins, and pneumonia infiltrations.
Results: A total of 56 patients were enrolled and randomized. The primary endpoint did not differ significantly between groups (A: 5.0 days, B: 4.0 days, C: 4.0 days), though the seven symptoms tended to disappear earlier in group A than group C (p = 0.08), and fatigue significantly decreased in group A (p = 0.005). Serum inflammatory cytokines, tumor necrosis factor (TNF)-α, granulocyte colony stimulating factor (G-CSF), interleukin (IL)-7, IL-15, and proliferation factors, transforming growth factor (TGF)-α, fibroblast growth factor (FGF)-2, and fms-like tyrosine kinase 3 ligand (Flt3-L), significantly decreased in group A. IL-8 and IFN-γ in nasal drip significantly decreased in both group A and B. Serious adverse events did not increase in CAM groups, though mild gastrointestinal and liver events occurred in group A.
Conclusion: CAM is safe and potentially useful for improving partial COVID-related symptoms and exerting immunomodulation during COVID-19 pneumonia.
Trial registration: Japan Registry of Clinical Trials (jRCT; registration number: jRCTs071210011; https://jrct.mhlw.go.jp/latest-detail/jRCTs071210011) on April 13, 2021.
Keywords: clarithromycin; coronavirus disease 2019 (COVID-19); cytokines; fatigue; long COVID; pneumonia.
. 2026 Mar 15:13:20499361261431488.
doi: 10.1177/20499361261431488. eCollection 2026 Jan-Dec.
Symptom relief and cytokine modulation by clarithromycin in mild COVID-19 pneumonia: an exploratory, multicenter, randomized-controlled open-label trial (CAME-COVID study)
Kazuko Yamamoto[SUP] 1 2 [/SUP], Naoki Iwanaga[SUP] 1 [/SUP], Asuka Umemura[SUP] 3 [/SUP], Toyomitsu Sawai[SUP] 4 [/SUP], Makoto Sumiyoshi[SUP] 5 [/SUP], Kohji Hashiguchi[SUP] 6 [/SUP], Yusuke Mori[SUP] 7 [/SUP], Hiroshi Ishii[SUP] 8 [/SUP], Yoji Futsuki[SUP] 9 [/SUP], Maiko Kiyohara[SUP] 1 [/SUP], Kenji Ota[SUP] 10 [/SUP], Kosuke Kosai[SUP] 10 [/SUP], Daisuke Sasaki[SUP] 10 [/SUP], Yuki Takamatsu[SUP] 11 [/SUP], Shingo Inoue[SUP] 11 [/SUP], Kouichi Morita[SUP] 11 [/SUP], Shin Tsutsui[SUP] 12 [/SUP], Kazuto Ashizawa[SUP] 13 [/SUP], Takahiro Takazono[SUP] 1 [/SUP], Noriho Sakamoto[SUP] 1 [/SUP], Naoki Hosogaya[SUP] 1 [/SUP], Masato Tashiro[SUP] 14 15 [/SUP], Takeshi Tanaka[SUP] 14 [/SUP], Koichi Izumikawa[SUP] 15 [/SUP], Katsunori Yanagihara[SUP] 10 [/SUP], Hiroshi Mukae[SUP] 1 [/SUP]
Affiliations
- PMID: 41884792
- PMCID: PMC13009641
- DOI: 10.1177/20499361261431488
Background: Coronavirus disease 2019 (COVID-19) remains an epidemic worldwide, and long COVID is a major social concern. Therapeutic options for relieving symptoms of COVID-19 pneumonia are limited. Clarithromycin (CAM), a macrolide antimicrobial, also functions as an immunomodulator.
Objectives: To assess the efficacy of CAM in improving clinical symptoms and attenuating inflammation in patients with mild COVID-19, with the aim of preventing progression to severe disease.
Design: An exploratory, multicenter, randomized-controlled, open-label trial.
Methods: This trial enrolled patients with mild COVID-19 pneumonia without oxygen supplementation from May 2021 through February 2022 in eight hospitals in Japan. Patients were randomly assigned in a 1:1:1 ratio to groups A (CAM 800 mg/day, 7 days), B (CAM 400 mg/day, 7 days), or C (standard treatment). The primary endpoint was the number of days required for 50% improvement in seven symptoms (fatigue, headache, cough, shortness of breath, taste/smell disturbance, and general unwellness) based on severity scores. Secondary endpoints included inflammatory cytokines, viral load, immunoglobulins, and pneumonia infiltrations.
Results: A total of 56 patients were enrolled and randomized. The primary endpoint did not differ significantly between groups (A: 5.0 days, B: 4.0 days, C: 4.0 days), though the seven symptoms tended to disappear earlier in group A than group C (p = 0.08), and fatigue significantly decreased in group A (p = 0.005). Serum inflammatory cytokines, tumor necrosis factor (TNF)-α, granulocyte colony stimulating factor (G-CSF), interleukin (IL)-7, IL-15, and proliferation factors, transforming growth factor (TGF)-α, fibroblast growth factor (FGF)-2, and fms-like tyrosine kinase 3 ligand (Flt3-L), significantly decreased in group A. IL-8 and IFN-γ in nasal drip significantly decreased in both group A and B. Serious adverse events did not increase in CAM groups, though mild gastrointestinal and liver events occurred in group A.
Conclusion: CAM is safe and potentially useful for improving partial COVID-related symptoms and exerting immunomodulation during COVID-19 pneumonia.
Trial registration: Japan Registry of Clinical Trials (jRCT; registration number: jRCTs071210011; https://jrct.mhlw.go.jp/latest-detail/jRCTs071210011) on April 13, 2021.
Keywords: clarithromycin; coronavirus disease 2019 (COVID-19); cytokines; fatigue; long COVID; pneumonia.