Fluoxetine and Sertraline Potently Neutralize the Replication of Distinct SARS-CoV-2 Variants (preprint)

The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. Previous studies have demonstrated the efficacy of functional inhibitors of acid sphingomyelinase (FIASMA) against infections with various viruses, including early variants of SARS-CoV-2. This work investigated whether the acid sphingomyelinase inhibitors fluoxetine and sertraline, usually used as antidepressant molecules in clinical practice, can inhibit the replication of the former and recently emerged SARS-CoV-2 variants in vitro. Fluoxetine and sertraline potently inhibited the infection with pseudotyped virus like particles and SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1 and omicron BA.5. These results highlight fluoxetine and sertraline as priority candidates for large-scale phase 3 clinical trials at different stages of SARS-CoV-2 infections, either alone or in combination with other medications.

Delayed Fatal Pulmonary Hemorrhage Following COVID-19 Vaccination: Case Report, Batch Analysis, And Proposed Autopsy Checklist (preprint)

We present a case of a 47-year-old male who died unexpectedly from acute pulmonary hemorrhage 555 days after completing the BNT162b2 (Pfizer) COVID-19 vaccination primary series. Before death, he exhibited symptoms of a mild respiratory infection. Despite a healthy medical history and no medication use, the patient’s condition rapidly deteriorated and he experienced severe respiratory distress, followed by cardiopulmonary arrest with evidence of profuse pulmonary bleeding. Autopsy findings revealed massive lung congestion without embolism, normal heart size, moderate coronary atherosclerosis without myocardial infarction, and no evidence of other hemorrhagic events. The patient tested negative for COVID-19 and other respiratory pathogens at autopsy. Despite these findings, the medical examiner determined the cause of death was attributed to atherosclerotic and hypertensive cardiovascular disease, without considering the recent pulmonary hemorrhage and unremarkable medical history. Investigation into the vaccine batch indicated a higher-than-average number of serious adverse events, including fatalities. The patient's BNT162b2 batch was among the top 2.8% for reported deaths. Moreover, the autopsy failed to investigate potential contributions from the vaccine, such as the presence of the Spike protein or related antibodies. The evidence suggests that the pulmonary hemorrhage, exacerbated by a viral infection, was the immediate cause of death, with the COVID-19 vaccine potentially playing a role in the development of cardiopulmonary pathology and hemorrhage. We propose autopsy protocols for COVID-19 vaccine recipients to better investigate vaccine-related pathologies among those with one or more prior injections.

Network-based integrative multi-omics approach reveals biosignatures specific to COVID-19 disease phases. (preprint)

Background: COVID-19 disease is characterized by a spectrum of disease phases (mild, moderate, and severe). Each disease phase is marked by changes in omics profiles with corresponding changes in the expression of features (biosignatures). However, integrative analysis of multiple omics data from different experiments across studies to investigate biosignatures at various disease phases is limited. Exploring an integrative multi-omics profile analysis through a network approach could be used to determine biosignatures associated with specific disease phases and enable the examination of the relationships between the biosignatures. Aim: To identify and characterize biosignatures underlying various COVID-19 disease phases in an integrative multi-omics data analysis. Method: We leveraged the correlation network approach to integrate transcriptomics, metabolomics, proteomics, and lipidomics data. The World Health Organization (WHO) Ordinal Scale (WOS) was used as a disease severity reference to harmonize COVID-19 patient metadata across two studies with independent data. A unified COVID-19 knowledge graph was constructed by assembling a disease-specific interactome from the literature and databases. Disease-state omics-specific graphs were constructed by integrating multi-omics data with the unified COVID-19 knowledge graph. We expanded on the network layers of multiXrank, a random walk with restart on multilayer network algorithm, to explore disease state omics-specific graphs and perform enrichment analysis. Results: Network analysis revealed the biosignatures involved in inducing chemokines and inflammatory responses as hubs in the severe and moderate disease phases. We observed more shared biosignatures between severe and moderate disease phases as compared to mild-moderate and mild-severe disease phases. We further identified both biosignatures that discriminate between the disease states and interactions between biosignatures that are either common between or associated with COVID-19 disease phases. Interestingly, cross-layer interactions between different omics profiles increased with disease severity. Conclusion: This study identified both biosignatures of different omics types enriched in disease-related pathways and their associated interactions that are either common between or unique to mild, moderate, and severe COVID-19. These biosignatures include molecular features that underlie the observed clinical heterogeneity of COVID-19 and emphasize the need for disease-phase-specific treatment strategies. In addition, the approach implemented here can be used for other diseases.

Teamwork in the time of COVID-19.

Strong and effective clinical teamwork has been shown to improve medical outcomes and reduce medical errors. Incorporating didactic and clinical activities into undergraduate medical education in which students work in teams will develop skills to prepare them to work in clinical teams as they advance through their education and careers. At the Yale School of Medicine, we foster the development of team skills in the classroom through team-based learning (TBL) and in clinical settings with the Interprofessional Longitudinal Clinical Experience (ILCE). Both TBL and ILCE require students work in close physical proximity. The COVID-19 pandemic forced us to immediately adapt our in-person activities to an online format and then develop clinical and interprofessional experiences that adhere to social distancing guidelines. Here we describe our approaches to solving these problems and the experiences of our students and faculty.

Cognitive predictors of COVID-19 mitigation behaviors in vaccinated and unvaccinated general population members.

BACKGROUND: Given the long-term threat posed by COVID-19, predictors of mitigation behaviors are critical to identify. Prior studies have found that cognitive factors are associated with some COVID-19 mitigation behaviors, but few studies employ representative samples and no prior studies have examined cognitive predictors of vaccination status. The purpose of the present study was to examine associations between cognitive variables (executive function, delay discounting, and future orientation) and COVID-19 mitigation behaviors (mask wearing, social distancing, hand hygiene and vaccination) in a population representative sample. METHODS: A population representative sample of 2,002 adults completed validated measures of delay discounting, future orientation, and executive function. Participants also reported frequency of mitigation behaviors, vaccination status, and demographics. RESULTS: Future orientation was associated with more mask wearing (ß = 0.160, 95 % CI [0.090, 0.220], p < 0.001), social distancing (ß = 0.150, 95 % CI [0.070, 0.240], p < 0.001), hand hygiene behaviors (ß = 0.090, 95 % CI [0.000, 0.190], p = 0.054), and a higher likelihood of being fully vaccinated (OR = 0.80, 95 % CI [0.670, 0.970], p = 0.020). Lower delay discounting predicted more consistent mask wearing (ß = -0.060, 95 % CI[-0.120, -0.010], p = 0.032) and being fully vaccinated (OR = 1.28, 95 % CI [1.13, 1.44], p < 0.001), while more symptoms of executive dysfunction predicted less mask wearing (ß = -0.240, 95 % CI [-0.320, -0.150] p < 0.001) and hand hygiene (ß = -0.220, 95 % CI [-0.320, -0.130], p < 0.001), but not vaccination status (OR = 0.96, 95 % CI [0.80, 1.16], p = 0.690) or social distancing behaviors (ß = -0.080, 95 % CI [-0.180, 0.020], p = 0.097). Overall, social distancing was the least well-predicted outcome from cognitive factors, while mask wearing was most well-predicted. Vaccination status was not a significant moderator of these effects of cognitive predictors on mitigation behaviors. CONCLUSIONS: Cognitive variables predict significant variability in mitigation behaviors. regardless of vaccination status. In particular, thinking about the future and discounting it less may encourage more consistent implementation of mitigating behaviors.

Do the vaccinated perform less distancing, mask wearing and hand hygiene? A test of the risk compensation hypothesis in a representative sample during the COVID-19 pandemic.

The "risk compensation hypothesis" holds that vaccinated individuals may be less motivated to protect themselves using other COVID-19 mitigation behaviors-e.g., masking, distancing and hand hygiene-given that they may percieve thier infection risk to be lower. The current investigation provides an empirical test of the risk compensation hypothesis in the COVID-19 context using prospective data from the Canadian COVID-19 Experiences Survey (CCES). The survey comprised 1,958 unvaccinated and fully vaccinated individuals drawn from a representative sample, using quota sampling to ensure substantial representation of unvaccinated individuals. Two waves of data were collected 6 months apart. Findings revealed that vaccinated individuals performed COVID-19 mitigation behaviors significantly more frequently than their unvaccinated counterparts, and they also showed lower rates of attenuation as the pandemic continued. In summary, our findings do not support the risk compensation hypothesis; instead they support the notion that people adopt vaccination and other protective behaviors in parallel.

Associations between social COVID-19 exposure and psychological functioning.

The negative consequences of the COVID-19 pandemic on mental health have been widely reported, but less is known about how the impact of COVID-19 on others in one's social circle shapes these high distress levels. This study examines associations between social COVID-19 exposure-knowing someone who had a COVID-19 infection-and psychological functioning, as well as whether socio-demographic factors moderate these relationships. In June 2020, respondents (N = 343) from clinics in Tampa, Florida, U.S.A. reported whether they had social COVID-19 exposure, anxiety, depression, and stress, and other COVID-19-related concerns. Social COVID-19 exposure was associated with increased anxiety, stress, and concerns about a family member getting sick, and concerns about drinking and substance use. Several associations between exposure and psychological functioning were stronger in women, younger people, and people with lower income, implying these groups face elevated psychological risks due to the pandemic, and should be prioritized in mental health recovery efforts.

Adsorption of Favipiravir on pristine graphene nanosheets as a drug delivery system: a DFT study.

The efficiency of pristine graphene (GN) in the delivery process of the Favipiravir (FPV) anti-COVID-19 drug was herein revealed within the FPV⋯GN complexes in perpendicular and parallel configurations in terms of the density functional theory (DFT) method. Adsorption energy findings unveiled that the parallel configuration of FPV⋯GN complexes showed higher desirability than the perpendicular one, giving adsorption energy up to -15.95 kcal mol-1. This favorability could be interpreted as a consequence of the contribution of π-π stacking to the overall strength of the adsorption process in the parallel configuration. Frontier molecular orbitals (FMO) findings demonstrated the ability of the GN nanosheet to adsorb the FPV drug by the alteration in the EHOMO, ELUMO, and Egap values before and after the adsorption process. Based on Bader charge results, the FPV drug and GN sheet exhibited electron-donating and -accepting characters, respectively, which was confirmed by the negative sign of the computed charge transfer (Qt) values. The FPV(R)⋯T@GN complex showed the most desirable Qt value of -0.0377e, which was in synoptic with the adsorption energy pattern. Electronic properties of GN were also altered after the adsorption of the FPV drug in both configurations, with more observable changes in the parallel one. Interestingly, the Dirac point of the GN sheet coincided with the Fermi level after the adsorption process, indicating that the adsorption process unaffected the presence of the Dirac point. The occurrence of the adsorption process was also noticed by the existence of new bands and peaks in the band structure and DOS plots, respectively. Short recovery time rendered the GN nanosheet an efficient FPV drug delivery system. The obtained findings provide new insight into the biomedical applications of the GN sheet as a promising drug delivery system.

Social cognitive predictors of vaccination status, uptake and mitigation behaviors in the Canadian COVID-19 Experiences survey.

Emerging infectious diseases like COVID-19 will remain a concern for the foreseeable future, and determinants of vaccination and other mitigation behaviors are therefore critical to understand. Using data from the first two waves of the Canadian COVID-19 Experiences Survey (CCES; N = 1,958; 66.56 % female), we examined social cognitive predictors of vaccination status, transition to acceptance and mitigation behaviors in a population-representative sample. Findings indicated that all social cognitive variables were strong predictors of mitigation behavior performance at each wave, particularly among unvaccinated individuals. Among those who were vaccine hesitant at baseline, most social cognitive variables predicted transition to fully vaccinated status at follow-up. After controlling for demographic factors and geographic region, greater odds of transitioning from unvaccinated at CCES Wave 1 to fully vaccinated at CCES Wave 2 was predicted most strongly by a perception that one's valued peers were taking up the vaccine (e.g., dynamic norms (OR = 2.13 (CI: 1.54,2.93)), perceived effectiveness of the vaccine (OR = 3.71 (CI: 2.43,5.66)), favorable attitudes toward the vaccine (OR = 2.80 (CI: 1.99,3.95)), greater perceived severity of COVID-19 (OR = 2.02 (CI: 1.42,2.86)), and stronger behavioral intention to become vaccinated (OR = 2.99 (CI: 2.16,4.14)). As a group, social cognitive variables improved prediction of COVID-19 mitigation behaviors (masking, distancing, hand hygiene) by a factor of 5 compared to demographic factors, and improved prediction of vaccination status by a factor of nearly 20. Social cognitive processes appear to be important leverage points for health communications to encourage COVID-19 vaccination and other mitigation behaviors, particularly among initially hesitant members of the general population.

SARS-CoV-2 seroprevalence among blood donors in Uganda: 2019-2022.

BACKGROUND: The true burden of COVID-19 in low- and middle-income countries remains poorly characterized, especially in Africa. Even prior to the availability of SARS-CoV-2 vaccines, countries in Africa had lower numbers of reported COVID-19 related hospitalizations and deaths than other regions globally. METHODS: Ugandan blood donors were evaluated between October 2019 and April 2022 for IgG antibodies to SARS-CoV-2 nucleocapsid (N), spike (S), and five variants of the S protein using multiplexed electrochemiluminescence immunoassays (MesoScale Diagnostics, Rockville, MD). Seropositivity for N and S was assigned using manufacturer-provided cutoffs and trends in seroprevalence were estimated by quarter. Statistically significant associations between N and S antibody seropositivity and donor characteristics in November-December 2021 were assessed by chi-square tests. RESULTS: A total of 5393 blood unit samples from donors were evaluated. N and S seropositivity increased throughout the pandemic to 82.6% in January-April 2022. Among seropositive individuals, N and S antibody levels increased ≥9-fold over the study period. In November-December 2021, seropositivity to N and S antibody was higher among repeat donors (61.3%) compared with new donors (55.1%; p = .043) and among donors from Kampala (capital city of Uganda) compared with rural regions (p = .007). Seropositivity to S antibody was significantly lower among HIV-seropositive individuals (58.8% vs. 84.9%; p = .009). CONCLUSIONS: Despite previously reported low numbers of COVID-19 cases and related deaths in Uganda, high SARS-CoV-2 seroprevalence and increasing antibody levels among blood donors indicated that the country experienced high levels of infection over the course of the pandemic.

No Substrate Left behind-Mining of Shotgun Proteomics Datasets Rescues Evidence of Proteolysis by SARS-CoV-2 3CLpro Main Protease.

Proteolytic processing is the most ubiquitous post-translational modification and regulator of protein function. To identify protease substrates, and hence the function of proteases, terminomics workflows have been developed to enrich and detect proteolytically generated protein termini from mass spectrometry data. The mining of shotgun proteomics datasets for such 'neo'-termini, to increase the understanding of proteolytic processing, is an underutilized opportunity. However, to date, this approach has been hindered by the lack of software with sufficient speed to make searching for the relatively low numbers of protease-generated semi-tryptic peptides present in non-enriched samples viable. We reanalyzed published shotgun proteomics datasets for evidence of proteolytic processing in COVID-19 using the recently upgraded MSFragger/FragPipe software, which searches data with a speed that is an order of magnitude greater than many equivalent tools. The number of protein termini identified was higher than expected and constituted around half the number of termini detected by two different N-terminomics methods. We identified neo-N- and C-termini generated during SARS-CoV-2 infection that were indicative of proteolysis and were mediated by both viral and host proteases-a number of which had been recently validated by in vitro assays. Thus, re-analyzing existing shotgun proteomics data is a valuable adjunct for terminomics research that can be readily tapped (for example, in the next pandemic where data would be scarce) to increase the understanding of protease function and virus-host interactions, or other diverse biological processes.

The Complex Association between COPD and COVID-19.

Chronic obstructive pulmonary disease (COPD) is significant cause of morbidity and mortality worldwide. There is mounting evidence suggesting that COPD patients are at increased risk of severe COVID-19 outcomes; however, it remains unclear whether they are more susceptible to acquiring SARS-CoV-2 infection. In this comprehensive review, we aim to provide an up-to-date perspective of the intricate relationship between COPD and COVID-19. We conducted a thorough review of the literature to examine the evidence regarding the susceptibility of COPD patients to COVID-19 infection and the severity of their disease outcomes. While most studies have found that pre-existing COPD is associated with worse COVID-19 outcomes, some have yielded conflicting results. We also discuss confounding factors such as cigarette smoking, inhaled corticosteroids, and socioeconomic and genetic factors that may influence this association. Furthermore, we review acute COVID-19 management, treatment, rehabilitation, and recovery in COPD patients and how public health measures impact their care. In conclusion, while the association between COPD and COVID-19 is complex and requires further investigation, this review highlights the need for careful management of COPD patients during the pandemic to minimize the risk of severe COVID-19 outcomes.

External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.

BACKGROUND: Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa. METHODS: An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days. RESULTS: Of the 446 084 patients, 15 397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage. CONCLUSION: No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.

RNA analysis of tape strips to rule out melanoma in lesions clinically assessed as cutaneous malignant melanoma: A diagnostic study.

BACKGROUND: Distinguishing cutaneous malignant melanoma (CMM) from nevi can be clinically challenging. Suspicious lesions are therefore excised, resulting in many benign lesions being removed surgically to find 1 CMM. It has been proposed to use tape strip derived ribonucleic acid (RNA) to distinguish CMM from nevi. OBJECTIVE: To develop this technique further and validate if RNA profiles can rule out CMM in clinically suspicious lesions with 100% sensitivity. METHODS: Before surgical excision, 200 lesions clinically assessed as CMM were tape stripped. Expression levels of 11 genes on the tapes were investigated by RNA measurement and used in a rule-out test. RESULTS: Histopathology showed that 73 CMMs and 127 non-CMMs were included. Our test correctly identified all CMMs (100% sensitivity) based on the expression levels of 2 oncogenes, PRAME and KIT, relative to a housekeeping gene. Patient age and sample storage time were also significant. Simultaneously, our test correctly excluded CMM in 32% of non-CMM lesions (32% specificity). LIMITATIONS: Our sample contained a very high proportion of CMMs, perhaps due to inclusion during COVID-19 shutdown. Validation in a separate trial must be performed. CONCLUSION: Our results demonstrate that the technique can reduce removal of benign lesions by one-third without overlooking any CMMs.

Fighting pandemics: Collaborative governance in development perspective

As the fight against COVID-19 marked its second anniversary in March, collaboration gained attention as a tool for preparedness and response. Most collaborative models derive from industrialized countries, and coverage in outlets remains focused on the Global North. To complement existing studies, the article asks how collaboration looks like in a development setting. It analyzes the policies of Global South countries, focusing on Africa, where the pandemic is shifting. By exploring responses there and highlighting complexities that familiar governing paths struggle to resolve, it posits whether the pandemic could spur change. It concludes by discussing lessons and suggesting ways to improve collaboration. [ FROM AUTHOR] Copyright of Administrative Theory & Praxis (Taylor & Francis Ltd) is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

An ACAT inhibitor suppresses SARS-CoV-2 replication and boosts antiviral T cell activity.

The severity of disease following infection with SARS-CoV-2 is determined by viral replication kinetics and host immunity, with early T cell responses and/or suppression of viraemia driving a favourable outcome. Recent studies uncovered a role for cholesterol metabolism in the SARS-CoV-2 life cycle and in T cell function. Here we show that blockade of the enzyme Acyl-CoA:cholesterol acyltransferase (ACAT) with Avasimibe inhibits SARS-CoV-2 pseudoparticle infection and disrupts the association of ACE2 and GM1 lipid rafts on the cell membrane, perturbing viral attachment. Imaging SARS-CoV-2 RNAs at the single cell level using a viral replicon model identifies the capacity of Avasimibe to limit the establishment of replication complexes required for RNA replication. Genetic studies to transiently silence or overexpress ACAT isoforms confirmed a role for ACAT in SARS-CoV-2 infection. Furthermore, Avasimibe boosts the expansion of functional SARS-CoV-2-specific T cells from the blood of patients sampled during the acute phase of infection. Thus, re-purposing of ACAT inhibitors provides a compelling therapeutic strategy for the treatment of COVID-19 to achieve both antiviral and immunomodulatory effects. Trial registration: NCT04318314.

Engaging Multistakeholder Perspectives to Identify Patient-Centered Research Priorities Regarding Vaccine Uptake Among Adults With Autoimmune Conditions.

OBJECTIVE: The study objective was to prioritize topics for future patient-centered research to increase uptake of common vaccines, such as for pneumococcal pneumonia, influenza, herpes zoster, human papillomavirus, and severe acute respiratory syndrome coronavirus 2, among adults living with autoimmune conditions. METHODS: A steering committee (SC) was formed that included clinicians, patients, patient advocates, and researchers associated with rheumatic diseases (psoriatic arthritis, rheumatoid arthritis, vasculitis), inflammatory bowel disease, and multiple sclerosis. Through a scoping review and discussions, SC members identified research topics regarding vaccine uptake and/or hesitancy for prioritization. A larger multistakeholder alliance that included patients and patient advocates, clinicians, researchers, policy makers, regulators, and vaccine manufacturers conducted a modified Delphi exercise online with three rating rounds and one ranking round. Frequency analysis and comparisons across stakeholder groups were conducted. A weighted ranking score was generated for each item in the ranking round for final prioritization. RESULTS: Through the Delphi process, 33 research topics were identified, of which 13 topics were rated as critical by more than 70% of all stakeholders (n = 31). The two highest ranked critical topics per the full stakeholder group were "How well a vaccine works for adults with autoimmune conditions" and "How beliefs about vaccine safety affect vaccine uptake." CONCLUSION: A multistakeholder group identified key topics as critically important priorities for future research to decrease vaccine hesitancy and improve uptake of vaccines for adults with autoimmune conditions.

Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update.

BACKGROUND: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway. METHODS: A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document. RESULTS: The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, Castleman's disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring. CONCLUSIONS: The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers.