Favorable changes of CT findings in a patient with COVID-19 pneumonia after treatment with tocilizumab

Cellina, Michaela; Orsi, Marcello; Bombaci, Francesco; Sala, Marc A.; Marino, Pietro; Oliva, Giancarlo

doi:10.1016/j.diii.2020.03.010

Cited by 96 publications

(92 citation statements)

References 2 publications

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“…To date, although other reports have shown favorable outcomes and imaging improvement after TCZ administration [21,22], the peculiarity of our case was the rapid (96 h) and impressive positive results after only a single dose of TCZ.…”

Section: Discussioncontrasting

confidence: 51%

Rapid and Impressive Response to a Combined Treatment with Single-Dose Tocilizumab and NIV in a Patient with COVID-19 Pneumonia/ARDS

Cascella

Mauro²,

Blasio³

et al. 2020

Medicina

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Treatment of acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia (CARDS) represents a clinical challenge, requiring often invasive mechanical ventilation (IMV). Since the pathogenesis of CARDS it probably involves a direct viral attack to pulmonary and endothelium cells, and immune-mediated inflammation with dysfunctional coagulation, it was suggested to interfere with interleukin-6 (IL-6) activity by using the IL-6 receptor monoclonal antibody tocilizumab (TCZ). We reported the case of a 54-year-old 100 kg male COVID-19 patient (BMI 29) with severe respiratory insufficiency featuring dyspnea and hypoxia (SpO2 89% on room; PaO2 53 mmHg). Despite treatment with antiviral and non-invasive ventilation (NIV), after 24 h there was a progressive worsening of clinical conditions with higher fever (40 °C), increased dyspnea, and hypoxia (PaO2/FiO2 or P/F ratio of 150). The patient was at the limit to be sedated and intubated for IMV. He was treated with tocilizumab (8 mg/Kg i.v., single shot 800 mg) and NIV in the prone positioning. After only 96 h, the clinical, laboratory, and imaging findings showed incredible improvement. There was an important gain in oxygenation (P/F 300), a decrease of C-reactive protein values, and a decrease of the fever. Both the neutrophil-to-lymphocyte ratio (NLR) and the derived NLR ratio dropped down to 44%. Chest imaging confirmed the favorable response. This case suggested that for CARDS management efforts are needed for reducing its underlying inflammatory processes. Through a multiprofessional approach, the combination of IL-6-targeting therapies with calibrated ventilatory strategies may represent a winning strategy for improving outcomes.

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Section: Discussioncontrasting

confidence: 51%

Rapid and Impressive Response to a Combined Treatment with Single-Dose Tocilizumab and NIV in a Patient with COVID-19 Pneumonia/ARDS

Cascella

Mauro²,

Blasio³

et al. 2020

Medicina

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“…As a result, it is not clear yet whether IL-6 inhibitors can be used to prevent and treat the cytokine storm. Fortunately, several research groups have published a protocol for a RCT to assess the efficacy and safety of tocilizumab as treatment of COVID-19 ( Cellina et al., 2020 ; Fu et al., 2020 ; Rilinger et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Immunosuppressive Drugs and COVID-19: A Review

et al. 2020

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Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is currently unknown whether immunosuppressive drugs are advantageous or detrimental in patients with COVID-19. Immunosuppressive drugs could be harmful in the initial phase of COVID-19. In this phase, the host immune response is necessary to inhibit viral replication. However, immunosuppressive drugs might have a beneficial effect in the later, more severe phase of COVID-19. In this phase, an overshoot of the host immune response (the “cytokine storm”) can cause ARDS, multiorgan failure and mortality. Aim To summarize the available evidence on the effect of immunosuppressive drugs on infection with SARS-CoV-2. The effects of immunosuppressive drugs on similar pandemic coronaviruses may resemble the effects on SARS-CoV-2. Thus, we also included studies on the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) Methods The study protocol was registered in PROSPERO (registration number CRD42020181137). We included randomized controlled trials (RCTs), cohort studies with a control group and case-control studies concerning humans ≥ 18 years old. We also included in-vitro studies and animal studies with a control group. Results and Conclusion Sixty-nine studies were included. Interestingly, MPA inhibits SARS-CoV-2 replication in-vitro . Clinical studies are needed to confirm the inhibitory effect of MPA on SARS-CoV-2 replication in-vivo . There are indications that corticosteroids and IL-6 inhibitors, like tocilizumab, can reduce mortality and prevent mechanical ventilation in patients with COVID-19. However, observational studies have contradictory results and the risk of bias is high. Thus, these results have to be confirmed in high-quality clinical trials before these drugs can be implemented as standard care. Based on the positive results of CNIs, mTOR inhibitors and thiopurine analogues in in-vitro studies with SARS-CoV and MERS-CoV, it would be interesting to investigate their effects on SARS-CoV-2 replication.

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“…56 Understanding the mechanisms underlying different prognosis in children is essential for designing targeted therapies for COVID-19. targeting the CRS and hyperinflammatory status of lung destruction via anti-IL-6R antibodies, [218][219][220][221][222][223][224][225][226][227][228][229][230][231][232][233][234][235][236][237] IL-1R antagonists, [238][239][240] JAK-STAT inhibitors, 241 or inhibition of entrance by anti CD147 antibodies 237 and destruction of the virus via protective antibody delivered with convalescent plasma 51,54,66,133,134,242 (Table 2). Eculizumab targets complement protein C5 preventing activation of complement terminal complex, which was used off label in patients with SARS-CoV-2 infection and severe pneumonia or ARDS and is now evaluated in an ongoing trail (SOLID-C19).…”

Section: Kids Versus Adults: Mechanisms Explaining the Clinical Difmentioning

confidence: 99%

Immunology of COVID‐19: Mechanisms, clinical outcome, diagnostics, and perspectives—A report of the European Academy of Allergy and Clinical Immunology (EAACI)

Sokołowska

Łukasik

Agache

et al. 2020

Allergy

149

167

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With the worldwide spread of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS-CoV-2-induced coronavirus disease-19 (COVID-19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS-CoV-2 infection and COVID-19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multiorgan disease. The similarities of the human immune response to SARS-CoV-2 and the SARS-CoV and MERS-CoV are underlined. We also summarize known and potential SARS-CoV-2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular, and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender, and age in development of COVID-19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID-19 studies.

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Favorable changes of CT findings in a patient with COVID-19 pneumonia after treatment with tocilizumab

Cited by 96 publications

References 2 publications

Rapid and Impressive Response to a Combined Treatment with Single-Dose Tocilizumab and NIV in a Patient with COVID-19 Pneumonia/ARDS

Rapid and Impressive Response to a Combined Treatment with Single-Dose Tocilizumab and NIV in a Patient with COVID-19 Pneumonia/ARDS

Immunosuppressive Drugs and COVID-19: A Review

Immunology of COVID‐19: Mechanisms, clinical outcome, diagnostics, and perspectives—A report of the European Academy of Allergy and Clinical Immunology (EAACI)

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