Anti-IL-6 Receptor Antibody Treatment for Severe COVID-19 and the Potential Implication of IL-6 Gene Polymorphisms in Novel Coronavirus Pneumonia
TL;DR: It is confirmed that anti-IL-6R antibody treatment could effectively treat severe COVID-19-infected patients, marked by suppression of CRP and improvement of clinical symptoms, and suppression of IL-6 signalling cascade shows a promising therapy in severe forms of SARS-CoV-2 infection.
Abstract: Although severe acute respiratory virus 2 (SARS-CoV-2)-infected patients tend to present with mild to moderate symptoms, some may develop severe or life-threatening disease There remains an urgent need for efficacious management of COVID-19, because despite current ongoing clinical treatment trials, no effective treatments have been reported Previously, our analysis demonstrated that excessive inflammatory responses, marked by an elevated level of interleukin-6 (IL-6) and C- reactive protein (CRP), are strongly associated with COVID-19 progression Moreover, there is also a probable association between the disease progression observed in COVID-19 with IL-6 gene polymorphism
This article summarizes the cumulative evidence on the efficacy of anti-IL-6 receptor (anti-IL-6R) antibody among severe COVID-19-infected patients Additionally, a meta-analysis was also performed to estimate the association between IL-6 gene polymorphism with predisposition as well as disease severity of pneumonia in general Our analysis confirmed that anti-IL-6R antibody treatment could effectively treat severe COVID-19-infected patients, marked by suppression of CRP and improvement of clinical symptoms The second analysis showed that although IL- 6 gene polymorphism did not predispose to pneumonia, carrier status of the IL-6–174C allele is associated with a higher level of IL-6 production and pneumonia severity Altogether, our study strengthens the notion that IL-6 plays a pivotal role in COVID-19 progression, and suppression of IL-6 signalling cascade shows a promising therapy in severe forms of SARS-CoV-2 infection
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13 May 2020
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TL;DR: A review of studies evaluating the role of host (and viral) genetics in the immune response to coronaviruses, as well as the clinical outcome of coronavirus‐mediated disease, concludes by discussing research areas with current knowledge gaps and proposes several avenues for future scientific exploration.
Abstract: This article provides a review of studies evaluating the role of host (and viral) genetics (including variation in HLA genes) in the immune response to coronaviruses, as well as the clinical outcome of coronavirus-mediated disease. The initial sections focus on seasonal coronaviruses, SARS-CoV, and MERS-CoV. We then examine the state of the knowledge regarding genetic polymorphisms and SARS-CoV-2 and COVID-19. The article concludes by discussing research areas with current knowledge gaps and proposes several avenues for future scientific exploration in order to develop new insights into the immunology of SARS-CoV-2.
162 citations
TL;DR: Cytokines, small proteins required in cell signaling and as immunomodulating agents in human body and known to mediate many inflammatory processes in the lungs are studied.
Abstract: Cytokines, small proteins (∼5-20 kDa) required in cell signaling and as immunomodulating agents in human body. Now, these cell signals are known to mediate many inflammatory processes in the lungs ...
31 citations
Cites methods from "Anti-IL-6 Receptor Antibody Treatme..."
...A meta-analysis was also conducted to relate the IL6 gene polymorphism with predisposition as well as disease severity of pneumonia, suggested the carrier status of IL6 174 C allele with higher IL-6 production and pneumonia severity (Ulhaq & Soraya, 2020)....
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TL;DR: In this paper, the authors investigated the genetic susceptibility factors to COVID-19 and its severity, including virus entry receptors, immune response, and inflammation-related genes, as well as the probable genetic predisposition models.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes novel coronavirus disease (COVID-19), is the seventh pathogenic coronavirus recently discovered in December 2019 in Wuhan, China. To date, our knowledge about its effect on the human host remains limited. It is well known that host genetic factors account for the individual differences in the susceptibility to infectious diseases. The genetic susceptibility factors to COVID-19 and its severity are associated with several unanswered questions. However, the experience gained from an earlier strain of coronavirus, SARS-CoV-1, which shows 78% genetic similarity to SARS-CoV-2 and uses the same receptor to bind to host cells, could provide some clues. It, therefore, seems possible to assemble new evidence in order to solve a potential genetic predisposition puzzle for COVID-19. In this chapter, the puzzle pieces, including virus entry receptors, immune response, and inflammation-related genes, as well as the probable genetic predisposition models to COVID-19, are discussed.
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TL;DR: A structured summary is provided including, as applicable, background, objectives, data sources, study eligibility criteria, participants, interventions, study appraisal and synthesis methods, results, limitations, conclusions and implications of key findings.
31,379 citations
TL;DR: Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.
Abstract: After analyzing the immune characteristics of patients with severe coronavirus disease 2019 (COVID-19), we have identified that pathogenic T cells and inflammatory monocytes with large amount of interleukin 6 secreting may incite the inflammatory storm, which may potentially be curbed through monoclonal antibody that targets the IL-6 pathways. Here, we aimed to assess the efficacy of tocilizumab in severe patients with COVID-19 and seek a therapeutic strategy. The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People’s Hospital were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography (CT) scan image, and laboratory examinations were retrospectively analyzed. Fever returned to normal on the first day, and other symptoms improved remarkably within a few days. Within 5 d after tocilizumab, 15 of the 20 patients (75.0%) had lowered their oxygen intake, and 1 patient needed no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% of patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% of patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% of patients (16/19). No obvious adverse reactions were observed. All patients have been discharged on average 15.1 d after giving tocilizumab. Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.
2,204 citations
TL;DR: TCZ appears to be an effective treatment option in COVID‐19 patients with a risk of cytokine storms and for these critically ill patients with elevated IL‐6, the repeated dose of the TCZ is recommended.
Abstract: Tocilizumab (TCZ), a monoclonal antibody against interleukin-6 (IL-6), emerged as an alternative treatment for COVID-19 patients with a risk of cytokine storms recently. In the present study, we aimed to discuss the treatment response of TCZ therapy in COVID-19 infected patients. The demographic, treatment, laboratory parameters of C-reactive protein (CRP) and IL-6 before and after TCZ therapy and clinical outcome in the 15 COVID-19 patients were retrospectively assessed. Totally 15 patients with COVID-19 were included in this study. Two of them were moderately ill, six were seriously ill and seven were critically ill. The TCZ was used in combination with methylprednisolone in eight patients. Five patients received the TCZ administration twice or more. Although TCZ treatment ameliorated the increased CRP in all patients rapidly, for the four critically ill patients who received an only single dose of TCZ, three of them (No. 1, 2, and 3) still dead and the CRP level in the rest one patient (No. 7) failed to return to normal range with a clinical outcome of disease aggravation. Serum IL-6 level tended to further spiked firstly and then decreased after TCZ therapy in 10 patients. A persistent and dramatic increase of IL-6 was observed in these four patients who failed treatment. TCZ appears to be an effective treatment option in COVID-19 patients with a risk of cytokine storms. And for these critically ill patients with elevated IL-6, the repeated dose of the TCZ is recommended.
1,069 citations
TL;DR: Clinical improvement and mortality were not statistically significant different between tocilizumab and standard treatment patients in this retrospective study on severe COVID-19 patients with hyper-inflammatory features.
345 citations
Journal Article•
TL;DR: In hospitalised adult patients with severe COVID-19, TCZ could be a safe option and an improvement in respiratory and laboratory parameters was observed, requiring future controlled trials to confirm the definite benefit with IL-6 target therapy.
Abstract: OBJECTIVES: No agent has yet been proven to be effective for the treatment of patients with severe COVID-19. METHODS: We conducted a pilot prospective open, single-arm multicentre study on off-label use of tocilizumab (TCZ) involving 63 hospitalised adult patients (56 males, age 62.6+/-12.5) with severe COVID-19. Clinical and laboratory parameters were prospectively collected at baseline, day 1, 2, 7 and 14. No moderate-to severe adverse events attributable to TCZ were recorded. RESULTS: We observed a significant improvement in the levels of ferritin, C-reactive protein, D-dimer. The ratio of the partial pressure of oxygen (Pa02) to the fraction of inspired oxygen (Fi02) improved (mean+/-SD Pa02/Fi02 at admission: 152+/-53; at day 7: 283.73 +/- 115.9, at day 14: 302.2 +/- 126, p<0.05). The overall mortality was 11%; D-dimer level at baseline, but not IL-6 levels were predictors of mortality. TCZ administration within 6 days from admission in the hospital was associated with an increased likelihood of survival (HR 2.2 95%CI 1.3-6.7, p<0.05). CONCLUSIONS: In hospitalised adult patients with severe COVID-19, TCZ could be a safe option. An improvement in respiratory and laboratory parameters was observed. Future controlled trials in patients with severe illness are urgently needed to confirm the definite benefit with IL-6 target therapy.
253 citations