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Background: Tocilizumab, an interleukin-6 inhibitor is part of many international guidelines for the management of cytokine storm associated with severe coronavirus disease 2019 with observed improvements. However, this drug is not recommended during pregnancy owing to the lack of safety data. Restriction of such medication use makes the management of coronavirus disease 2019 in pregnant women more challenging. Pregnant women are more likely to deteriorate from respiratory infections because of the immunological changes during pregnancy and the hypoxic compromise. We report the use of tocilizumab in two pregnant patients who developed severe coronavirus disease 2019 with a successful outcome. To date, there have not been any published data on tocilizumab use in pregnancy for cytokine storm syndrome associated with coronavirus disease 2019.Case Presentations: In 2020, two pregnant women of Asian origin in the last trimester of pregnancy were admitted to our hospital with severe coronavirus disease 2019. Their clinical condition progressed rapidly despite maximum supportive treatments. Blood testing in the second week of illness showed rising ferritin and interleukin-6 levels, indicating the possibility of cytokine storm syndrome. Both developed respiratory failure necessitating mechanical ventilation. Due to their critical clinical condition and lack of response to supportive treatment, a decision was made to use intravenous tocilizumab therapy. Both were treated with one intravenous infusion of tocilizumab and had a successful outcome. They were extubated later and gradually weaned off supplemental oxygen. The first patient continued with her pregnancy during the hospital stay with normal fetal scans. The second patient needed an emergency cesarean section and delivered a healthy infant.Conclusion: In critical clinical situations, tocilizumab may have a role in managing coronavirus disease 2019 related cytokine storm during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Due to the lack of proven therapies, we evaluated the effects of early administration of tocilizumab for COVID-19. By inhibition of the IL-6 receptor, tocilizumab may help to mitigate the hyperinflammatory response associated with progressive respiratory failure from SARS-CoV-2.Methods: A retrospective, observational study was conducted on hospitalized adults who received intravenous tocilizumab for COVID-19 between March 23, 2020 and April 10, 2020.Results: Most patients were male (66.7%), Hispanic (63.3%) or Black (23.3%), with a median age of 54 years. Tocilizumab was administered at a median of 8 days (range 1-21) after initial symptoms and 2 days (range 0-12) after hospital admission. Within 30 days from receiving tocilizumab, 36 patients (60.0%) demonstrated clinical improvement, 9 (15.0%) died, 33 (55.0%) were discharged alive, and 18 (30.0%) remained hospitalized. Successful extubation occurred in 13 out of 29 patients (44.8%). Infectious complications occurred in 16 patients (26.7%) at a median of 10.5 days. After tocilizumab was administered, there was a slight increase in PaO2/FiO2 and an initial reduction in CRP, but this effect was not sustained beyond day 10.Conclusions: Majority of patients demonstrated clinical improvement and were successfully discharged alive from the hospital after receiving tocilizumab. We observed a rebound effect with CRP, which may suggest the need for higher or subsequent doses to adequately manage cytokine storm. Based on our findings, we believe that tocilizumab may have a role in the early treatment of COVID-19, however larger randomized controlled studies are needed to confirm this. [ABSTRACT FROM AUTHOR]

A severe pneumonia-associated respiratory syndrome caused by a new coronavirus was identified in December 2019 (COVID-19), spread rapidly and has become a world-wide public health challenge. About 25% of COVID-19 patients experienced severe complications including acute respiratory distress syndrome (ARDS), and even progressed into an intensive care unit (ICU) admission and died. The exploration for the mortality causes and advancing novel therapeutic development of severe COVID-19 is crucial at the moment. The biopsy samples analysis at autopsy suggested that increased alveolar exudate caused by aberrant host immune response and inflammatory cytokine storm probably impedes alveolar gas exchange and contributes to the high mortality of severe COVID-19 patients. Our research has identified that pathogenic T cells and inflammatory monocytes incite inflammatory storm with large amount of interleukin 6, therefore monoclonal antibody that targets the IL-6 pathways may potentially curb inflammatory storm. Moreover, Tocilizumab treatment that blocking IL-6 receptors showed inspiring clinical results including temperature returned to normal quickly and respiratory function improved. Therefore, we suggest that Tocilizumab is an effective treatment in severe patients of COVID-19 to calm the inflammatory storm and reduce mortality. [ABSTRACT FROM AUTHOR]

Background: Cytokine storm triggered by Severe Coronavirus Disease 2019 (COVID-19) is associated with high mortality. With high Interleukin -6 (IL-6) levels reported in COVID-19 related deaths in China, IL-6 is considered to be the key player in COVID-19 cytokine storm. Tocilizumab, a monoclonal antibody against IL-6 receptor, is used on compassionate grounds for treatment of COVID-19 cytokine storm. The aim of this study was to assess effect of tocilizumab on mortality due to COVID-19 cytokine storm.Method: This retrospective, observational study included patients of severe COVID-19 pneumonia with persistent hypoxia (defined as saturation 94% or less on supplemental Oxygen of 15 L per minute through non-rebreathing mask or PaO2/FiO2 ratio of less than 200) who were admitted to a tertiary care center in Mumbai, India, between 31st March to 5th July 2020. In addition to standard care, single Inj. Tocilizumab 400 mg was given intravenously to 151 consecutive COVID-19 patients with persistent hypoxia, from 13th May to 5th July 2020. These 151 patients were retrospectively analysed and compared with historic controls, ie consecutive COVID-19 patients with persistent hypoxia, defined as stated above (N = 118, from our first COVID-19 admission on 31st March to 12th May 2020 i.e., till tocilizumab was available in hospital). Univariate and multivariate Cox regression analysis was performed for identifying predictors of survival. Statistical analysis was performed using IBM SPSS version 26.Results: Out of 269 (151 in tocilizumab group and 118 historic controls) patients studied from 31st March to 5th July 2020, median survival in the tocilizumab group was significantly longer than in the control group; 18 days (95% CI, 11.3 to 24.7) versus 9 days (95% CI, 5.7 to 12.3); log rank p 0.007. On multivariate Cox regression analysis, independent predictors of survival were use of tocilizumab (HR 0.621, 95% CI 0.427-0.903, P 0.013) and higher oxygen saturation.Conclusion: Tocilizumab may improve survival in severe COVID-19 pneumonia with persistent hypoxia. Randomised controlled trials on use of tocilizumab as rescue therapy in patients of severe COVID-19 pneumonia with hypoxia (PaO2/FiO2 less than 200) due to hyperinflammatory state, are warranted. [ABSTRACT FROM AUTHOR]

We would like to comment on the article entitled "Association between cytokine profiles and lung injury in COVID-19 pneumonia" by Li-Da Chen and colleagues, with respect to emerging data regarding the immunopathogenesis of COVID-19. Chen et al. demonstrated the relevance of IL-2R, IL-6 and TNF-α in the cytokine storm and IL-6 as an independent predictor for COVID-19 severity. Del Valle et al. corroborated these findings with regard to IL-6 and disease severity, however, they also showed IL-8 to be of significance. This may be explained by the varying techniques used by the two studies to determine severity. Further studies including critically ill patients and the analysis of mortality rates in this patient cohort would greatly enhance the clinical relevance of these findings. As speculated by Chen et al., early studies on the use of tocilizumab in COVID-19 patients were promising, however, full results from ongoing trials are required to confirm a survival benefit in patients treated with tocilizumab. Moreover, investigating the roles of other pro-inflammatory cytokines and their impact on disease severity could potentially inform novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is characterized by fast deterioration in the mechanism of cytokine storm. Therefore, treatment with immunomodulating agents should be initiated as soon as hyperinflammation is established. Evidence for the use of tocilizumab (TCZ) in COVID-19 is emerging, but the drug in this setting is used "off label" with limited data on both effectiveness and safety. Therefore, Hospital for Infectious Diseases in Warsaw established a Standard Operating Procedure (SOP) for the use of TCZ in severe COVID-19 cases. Case presentation: Here, we present a case of 27-year-old, otherwise healthy man, who was successfully treated with chloroquine, azithromycin, tocilizumab and a standard of care. Initially the magnitude of lung devastation, clinical deterioration and the need for mechanical ventilation suggested unfavorable prognosis. However, we observed complete regression in radiological changes and rapid clinical improvement. Irrespective of this, patient's serum interleukin 6 and aminotransferases remained elevated even after a month from treatment. Conclusions: An overlapping effect of hyperinflammation, hypoxic organ injury and drug-related toxicity warrants a long-term follow-up for COVID-19 survivors. In addition, residual IL-6 receptors blockage may mask new infections. A standardized approach to follow-up for COVID-19 survivors is urgently needed. Current and future research should also investigate the impact of experimental therapies on lung tissue healing and regeneration, as well as long-term treatment toxicities. [ABSTRACT FROM AUTHOR]