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10.1002/jmv.26038

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32436994!7280615!32436994
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suck abstract from ncbi


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pmid32436994      J+Med+Virol 2020 ; 92 (11): 2516-2522
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  • Clinical outcomes in COVID-19 patients treated with tocilizumab: An individual patient data systematic review #MMPMID32436994
  • Antwi-Amoabeng D; Kanji Z; Ford B; Beutler BD; Riddle MS; Siddiqui F
  • J Med Virol 2020[Nov]; 92 (11): 2516-2522 PMID32436994show ga
  • BACKGROUND: Current evidence suggests an important role of the interleukin-6 (IL-6) pathway in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cytokine release storm in severely ill coronavirus disease 2019 (COVID-19) patients. Inhibition of the IL-6 pathway with tocilizumab has been employed successfully in some of these patients but the data is mostly consistent of case reports and series. METHODS: We performed a systematic search of PubMed, Embase, and Medline from 22nd April 2020 and again on 27th April 2020 using the following search terms alone or in combination: "COVID-19," "coronavirus," "SARS-CoV-2," "COVID," "anti-interleukin-6 receptor antibodies," "anti-IL-6," "tocilizumab," "sarilumab," "siltuximab." We included studies that reported individual patient data. We extracted and analyzed individual level data on baseline characteristics, laboratory findings, and clinical outcomes. The primary endpoint was in-hospital mortality. Secondary endpoints included in-hospital complications, recovery rates, effect of patient characteristics on the primary outcome and changes in levels of inflammatory markers. RESULTS: Three hundred fifty-two records were identified through a systematic search, of which 10 studies met the inclusion criteria. A single study currently under review was also added. Eleven observational studies encompassing 29 patients were included in the present review. There were more males (24 [82.8%]), and hypertension was the most common comorbidity (16 [48.3%]). Over an average of 5.4 hospital days, the primary endpoint occurred in 6 (20.7%) patients. Among surviving patients, about 10% had worsened disease and 17% recovered. The most common complication was acute respiratory distress syndrome (8 [27.6%]). The IL-6 level was significantly higher after the initiation of tocilizumab with median (interquartile range) of 376.6 (148-900.6) pg/mL compared to the baseline of 71.1 (31.9-122.8) pg/mL (P = .002). Mean (standard deviation) levels of C-reactive protein (CRP) were significantly decreased following treatment 24.6 (26.9) mg/L compared to baseline 140.4 (77) mg/L (P < .0001). Baseline demographics were not significantly different among survivors and nonsurvivors by Fisher's exact test. CONCLUSION: In COVID-19 patients treated with tocilizumab, IL-6 levels are significantly elevated, which are supportive of cytokine storm. Following initiation of tocilizumab, there is elevation in the IL-6 levels and CRP levels dramatically decrease, suggesting an improvement in this hyperinflammatory state. Ongoing randomized control trials will allow for further evaluation of this promising therapy. IMPORTANCE: Recent data indicate that severe COVID-19 causes a cytokine release storm and is associated with worse clinical outcomes and IL-6 plays an important role. It is suggestive that anti-IL-6 results in the improvement of this hyperinflammatory state. However, to our knowledge, there is no individual patient data systematic review performed to summarize baseline characteristics and clinical outcomes of COVID-19 patients who received tocilizumab.
  • |*Hospital Mortality[MESH]
  • |Antibodies, Monoclonal, Humanized/*therapeutic use[MESH]
  • |COVID-19/immunology/*therapy[MESH]
  • |Cytokine Release Syndrome/immunology/therapy[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Interleukin-6/*antagonists & inhibitors/immunology[MESH]
  • |Male[MESH]
  • |Observational Studies as Topic[MESH]
  • |Receptors, Interleukin-6/antagonists & inhibitors[MESH]
  • |Severity of Illness Index[MESH]
  • |Time Factors[MESH]


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