Outcome of early-stage combination treatment with favipiravir and methylprednisolone for severe COVID-19 pneumonia: A report of 11 cases

Murohashi, Kota; Hagiwara, Eri; Kitayama, Takaaki; Yamaya, Takafumi; Higa, Katsuyuki; Sato, Yozo; Otoshi, Ryota; Shintani, Ryota; Okabayashi, Hiroko; Ikeda, Satoshi; Niwa, Takashi; Nakazawa, Atsuhito; Oda, Toshiatsu; Okuda, Ryo; Sekine, Akimasa; Kitamura, Hideya; Baba, Tomohisa; Komatsu, Shigeru; Iwasawa, Tae; Kaneko, Takeshi; Ogura, Takashi

doi:10.1016/j.resinv.2020.08.001

Cited by 31 publications

(25 citation statements)

References 8 publications

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“…As of December 2020, the numbers of patients with COVID-19 and associated deaths are still rapidly increasing. Some existing drugs have been reported to be effective in patients with COVID-19 [ 1 , 2 , 3 ]. However, many patients with COVID-19 become severe or critical despite treatment with antiviral or anti-inflammatory drugs.…”

Section: Introductionmentioning

confidence: 99%

Serum Krebs von den Lungen-6 levels are associated with mortality and severity in patients with coronavirus disease 2019

Yamaya

Hagiwara

Baba

et al. 2021

Respiratory Investigation

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Background The serum Krebs von den Lungen-6 (KL-6) level is a predictive factor for acute respiratory distress syndrome (ARDS). The development of ARDS has been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to determine whether serum KL-6 levels are associated with mortality and severity in patients with COVID-19. Methods Among 361 Japanese patients with COVID-19 who were hospitalized at Kanagawa Cardiovascular and Respiratory Center between February 2020 and December 2020, 356 patients with data on serum KL-6 levels were enrolled and their medical records were retrospectively analyzed. Results A negative correlation was observed between KL-6 levels and the ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen on admission. The KL-6 levels on admission and the maximal KL-6 levels were higher in patients with severe disease (n = 60) than in those with nonsevere disease (n = 296). Furthermore, the maximal KL-6 levels were higher in nonsurvivors (n = 6) than in survivors (n = 350). In nonsurvivors, the KL-6 levels increased as the disease progressed. The optimal cutoff value of the maximal KL-6 level for discriminating between survivors and nonsurvivors was 684 U/mL, with a sensitivity of 83.3%, a specificity of 90.5%, and an area under the curve of 0.89. Conclusions The serum KL-6 level was associated with disease severity. Patients with KL-6 levels ≥ 684 U/mL had a significantly poorer outcome than those with KL-6 levels < 684 U/mL.

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Section: Introductionmentioning

confidence: 99%

Serum Krebs von den Lungen-6 levels are associated with mortality and severity in patients with coronavirus disease 2019

Yamaya

Hagiwara

Baba

et al. 2021

Respiratory Investigation

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“…It was reported that the use of dexamethasone in patients hospitalized with COVID-19 resulted in a lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone ( 6 ). We recently reported that the combined treatment of mPSL and favipiravir during the early stage of infection in patients with severe COVID-19 pneumonia may prevent aggravation ( 15 ), as seen in this case. We also used ciclesonide and nafamostat mesylate to anticipate an anti-viral effect and intravenous immunoglobulin to anticipate dual effects of immune substitution and immunomodulation.…”

Section: Discussionmentioning

confidence: 52%

COVID-19 Pneumonia Resembling an Acute Exacerbation of Interstitial Pneumonia

et al. 2020

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An 84-year-old man was admitted with hypoxemia and ground-glass opacities with traction bronchiectasis in both lungs and mild fibrosis on computed tomography. We first suspected that he had acute exacerbation of interstitial pneumonia and initiated methylprednisolone pulse therapy. On day 4, he was diagnosed with COVID-19 pneumonia. Although the ground-glass opacities were improved with corticosteroid treatment alone, the hypoxemia persisted, and the plasma D-dimer level increased. Anticoagulant therapy was initiated, and the hypoxemia was improved. COVID-19 pneumonia may result in radiological findings similar to those of acute exacerbation of interstitial pneumonia, and corticosteroids and anticoagulant therapy may lead to favorable outcomes.

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“…Authors conclude that in their pilot study, favipiravir appeared beneficious among moderately ill patients [16]. In small case series studies, favipiravir was administered with nafamostat mesylate or methylprednisolone for COVID-19 patients in different disease stages, but due to the lack of control groups and antiviral combination usage, the extent favipiravir effect on clinical cure remains ambiguous [17-19]. In all, we think that our findings could be reflected by data from current literature, and the role for favipiravir should not be overestimated in the treatment of adults with moderate to severe COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Role of favipiravir in the treatment of adult patients with moderate to severe COVID-19: a single-center, prospective, observational, sequential cohort study from Hungary

Szabó

Lenart²,

Petrik

et al. 2020

Preprint

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BackgroundPreliminary data suggests that favipiravir might have a role in COVID-19 treatment. Our aim was to assess the role of favipiravir in the treatment of COVID-19.MethodsA single-center, prospective, observational, sequential cohort study was performed among consecutive adults hospitalized with PCR-confirmed COVID-19 between March– July,2020. Patients were screened for inclusion by a priori criteria, and were included in the favipiravir cohort if SOC+FVP, or the non-favipiravir group if SOC±other antiviral medications without FVP were administered for >48 hours. Treatment allocation was done per national guidelines. For COVID-19 diagnosis and severity, ECDC and WHO definitions were utilized, and daily per protocol hospital follow-up was done. Primary composite end-point was disease progression (14-day all-cause death, need for mechanical ventilation, or immunomodulatory therapy). For statistical comparison, Fisher’s exact test and Mann– Whitney U-test were used.ResultsIn all, 75 patients were included per cohort. In the FVP cohort, chronic heart disease (36/75, 48.0% vs. 16/75, 21.3%, p<0.01) and diabetes mellitus (23/75, 30.7% vs. 10/75, 13.3%, p<0.01) were more prevalent, hospital LOS (18.5±15.5 days vs. 13.0±8.5 days, p<0.01) was higher. Disease progression (17/75, 22.7% vs. 10/75, 13.3%, p=0.13), 14-day all-cause death (9/75, 12.0% vs. 10/75, 13.3%, p=0.8) and need for mechanical ventillation (8/75, 10.7% vs. 4/75, 5.3%, p=0.22) were similar between groups. Immunomodulatory therapies were administered frequently among patients receiving FVP (10/75, 13.3% vs. 1/75, 1.3%, p<0.01).ConclusionsIn this study, favipiravir did not seem to affect disease progression. Further data are needed to position this drug among the anti-SARS-CoV-2 armamentarium.

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Outcome of early-stage combination treatment with favipiravir and methylprednisolone for severe COVID-19 pneumonia: A report of 11 cases

Cited by 31 publications

References 8 publications

Serum Krebs von den Lungen-6 levels are associated with mortality and severity in patients with coronavirus disease 2019

Serum Krebs von den Lungen-6 levels are associated with mortality and severity in patients with coronavirus disease 2019

COVID-19 Pneumonia Resembling an Acute Exacerbation of Interstitial Pneumonia

Role of favipiravir in the treatment of adult patients with moderate to severe COVID-19: a single-center, prospective, observational, sequential cohort study from Hungary

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