Using tocilizumab in sars COV-2 disease: Case report

Coronavirus 19 (COVID-19) may cause a cytokine release syndrome inducing the severity of the disease. Various immune modulating agents are suggested due to the lack of definitive treatment and vaccine. In this case report, we aimed to share the clinical course of a Covid 19 patient who was given tocilizumab (TCZ) for severe ARDS on the 5th day of hospitalization. Although, the patient was extubated 12 days after TCZ treatment with a rapid recovery, we believe that more cases are needed to determine the efficiency and timing of TCZ treatment.Copyright © 2020 Necati Ozpinar. All rights reserved.

Immunomodulatory therapies for COVID-19.

Purpose: As COVID-19 disease progresses, the host inflammatory response contributes to hypoxemia and severe and critical illness. In these latter stages of disease, patients may benefit from immunomodulatory therapies to control the aberrant host inflammatory response. In this review, we provide an overview of these therapies and provide summaries of the studies that led to issuance of FDA Emergency Use Authorization or recommendation by the Infectious Diseases Society of America (IDSA). Materials and methods: We reviewed English-language studies, Emergency Use Authorizations (EUAs), and guidelines from March 2020 to present. Conclusion and relevance: There are several therapies with proposed benefit in severe and critical COVID-19 disease. Few have been issued FDA EUA or recommendation by the Infectious Diseases Society of America (IDSA). Physicians should be familiar with the evidence supporting use of these therapies and the patient populations most likely to benefit from each.

COVID-19 and Autoimmune Demyelinating Diseases

This chapter addresses COVID-19 in the context of patients with demyelinating disorders of the central nervous system (CNS). Multiple sclerosis (MS) is the most common CNS demyelinating disease, and SARS-CoV-2 infection in patients with MS and other autoimmune demyelinating CNS disorders causes numerous concerns. As with other infectious diseases, COVID-19 may exacerbate pathology in patients with MS. Standard therapies for MS and immunosuppressive treatments for other CNS autoimmune disorders may pose unique risks during severe COVID-19. However, preliminary findings on SARS-CoV-2 infection suggest that some MS therapies may limit the aggressive immune response underlying severe COVID-19 complications. Furthermore, infection with SARS-CoV-2 may have the potential to trigger postinfection autoimmune disorders. Here we review the current understanding of COVID-19 in patients with MS and other CNS disorders and the impact of immunomodulatory therapies on these patients. © 2021 Elsevier Inc. All rights reserved.

THE RISK OF COVID-19 SEVERITY IN PATIENTS WITH MS APPEARS TO BE ASSOCIATED WITH IMMUNOTHERAPY

Immunomodulatory drugs are important to control disease activity in relapsing-remitting multiple sclerosis (MS).Anti-CD20-therapy is one of such medications. In Sweden, extensive off label prescription of rituximab (RTX) in MS hasbeen documented;it is presently prescribed for more than half of all treated MS patients. The rationale for the increasingprescription of RTX was previous data from phase II and observational studies supporting high efficacy and safety, in additionto the financial aspect. We report national data on usage of disease modifying therapies in MS patients and risk of severeCOVID-19 in association with RTX exposure within this group.The Swedish National MS Registry (SMSreg) aims to cover all patients with MS in the country, (n = approximately18,000). After COVID-19 pandemic started in Sweden, a new section was established in it to register clinical and demographicparameters in COVID-19-infected patients. Data presented in the current report were obtained from the SMSreg.A total of 85 out of approximately 6,000 RTX-treated Swedish MS patients had been hospitalized with COVID-19(as reported from the SMSreg, June 16, 2021) and adjusted analyses showed a 2–3 fold increase in a risk (OR = 2.89;p = 0.001) of hospitalization for anti-CD20 treated patients. A change of praxis was introduced in Sweden in spring2020, resulting in a majority of patients receiving RTX infusions with extended intervals in order to reduce the risk ofsevere COVID-19 infection.Current Swedish registry data suggest that exposure to RTX in MS may affect the clinical outcome of COVID-19 infection.These observations have rapidly impacted use of immunomodulatory drugs in Swedish MS patients © Iacobaeus E., Boström I., Zhukovsky Ch., Berntsson Sh.G., Landtblom A.-M., 2021

Systematic review of risk of SARS-CoV-2 infection and severity of COVID-19 with therapies approved to treat multiple sclerosis.

There is growing concern that multiple sclerosis (MS) patients on certain therapies may be at higher risk for severe coronavirus disease 2019 (COVID-19). We conducted a systematic literature review to examine the available data on U.S. therapies approved to treat MS and the risk of SARS-CoV-2 infection or severe COVID-19 outcomes. We conducted searches in PubMed, Embase, and the WHO COVID-19 database through May 2, 2021, and retrieved articles describing clinical data on therapies approved to treat MS and the risk of infection with SARS-CoV-2 or the effects of such therapies on clinical outcomes of COVID-19. The literature search identified a total of 411 articles: 97 in PubMed, 227 in Embase, and 87 in the WHO database. After excluding duplicates and screening, we identified 15 articles of interest. We identified an additional article through a broader secondary weekly search in PubMed. Thus, ultimately, we reviewed 16 observational studies. Available data, which suggest that MS patients treated with anti-CD20 monoclonal antibodies may be at increased risk for severe COVID-19, are subject to relevant limitations. Generally, studies did not identify increased risk for COVID-19 worsening with other therapies approved to treat MS. Based on observational data, biological plausibility, novelty of the drug-event association, and public health implications in a subpopulation with potential impaired response to the COVID-19 vaccines, this safety signal merits further monitoring.

Frequency, characteristics and outcome of corona virus disease 2019 (COVID-19) infection in Iranian patients with rheumatic diseases

Aim of the work to investigate the frequency, clinical characteristics and outcome of severe acute respiratory syndromecoronavirus 2(SARS-CoV-2) infection in rheumatic diseases patients. Patients and methods One thousand patients with rheumatic diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (SpA), systemic sclerosis (SSc), Sjögren’s syndrome (SS), Behçets disease (BD), vasculitis, idiopathic inflammatory myositis (IIM), relapsing polychondritis, sarcoidosis and antiphospholipid syndrome (APS) were studied. The following data were collected: age, sex, disease diagnosis, rheumatic disease medication. Rheumatic diseases patients were divided into two groups of infected and non-infected patients with COVID-19 and collected data were compared. Results The 1000 patients mean age was 43.4±13 years and 84.1% were females. The main diagnosis was RA (37.1%), followed by SLE (23.8%), SpA (13.4%), SSc (12.4%), vasculitis, BD and rhupus in 2.4%, 2.3% and 2.2% respectively, SS and SSc in 0.7% each. Most patients were taking glucocorticoids (78.4%). A large majority of patients were taking at least one of the cDMARDs. 16.1% were taking biologic therapy. 221 rheumatic diseases patients with COVID-19 were identified. Of these, 38 patients (17.2%) were hospitalized and 9 patients (4.1%) died. No significant difference was observed for compared variables in patients with and without COVID-19 except for prednisolone >20 mg/d (0.64% vs 2.26%;p=0.048). Conclusion Most rheumatic diseases do not seem to be a risk factor for developing COVID-19 infection and despite immunosuppressive therapies, there is no poorer outcome. Only, patients using prednisolone >20mg/d are at higher risk of developing COVID-19 infection.

Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies.

BACKGROUND: In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response. METHODS: We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech,Inc or mRNA-1273, Moderna Tx,Inc). A blood collection before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche-Diagnostics). The log-transform of the antibody levels was analyzed by multivariable linear regression. FINDINGS: 780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariable analysis, the antibody levels of patients on ocrelizumab (201-fold decrease (95%CI=128-317), p < 0·001), fingolimod (26-fold decrease (95%CI=16-42), p < 0·001) and rituximab (20-fold decrease (95%CI=10-43), p < 0·001) were significantly reduced as compared to untreated patients. Vaccination with mRNA-1273 resulted in a systematically 3·25-fold higher antibody level (95%CI=2·46-4·27) than with the BNT162b2 vaccine (p < 0·001). The antibody levels on anti-CD20 therapies correlated to the time since last infusion, and rituximab had longer intervals (mean=386 days) than ocrelizumab patients (mean=129 days). INTERPRETATION: In pwMS, anti-CD20 treatment and fingolimod led to a reduced humoral response to mRNA-based SARS-CoV-2 vaccines. As mRNA-1273 elicits 3·25-higher antibody levels than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 treatment or fingolimod. Combining our data with those on the cellular immune response to vaccines, and including clinical follow-up, will contribute to better define the most appropriate SARS-CoV-2 vaccine strategies in the context of DMTs and MS. FUNDING: FISM[2021/Special-Multi/001]; Italian Ministry of Health'Progetto Z844A 5 × 1000'.

Multiple sclerosis immunomodulatory therapies tested for effectiveness in COVID-19.

INTRODUCTION: The global pandemic of COVID-19 began in Wuhan, China in December 2019. Research into effective therapies has been conducted worldwide. Currently, there is no antiviral treatment and many patients develop a severe course of the disease, including severe respiratory failure. Due to similar pathomechanisms of inflammation in multiple sclerosis (MS) and COVID-19, immunomodulatory drugs that are registered for the treatment of MS are under study in the SARS-CoV-2 infection in clinical trials. MATERIALS AND METHODS: Using clinicaltrials.gov, we found information related to ongoing clinical studies on potential drugs for COVID-19 which are also used in MS therapy. The outcomes of several trials were published on pubmed.ncbi.nlm.nih.gov. RESULTS: There were 18 clinical trials evaluating the effectiveness and safety of interferon-ß, fingolimod, or leflunomide in COVID-19. Some trial outcomes available at pubmed.ncbi.nlm.nih.gov suggested an association of these drug treatments with improvements in signs and symptoms, and the disease course. CONCLUSION: The administration of immunomodulatory drugs in COVID-19 may result in potential beneficial effects probably associated with their anti-inflammatory and antiviral properties. Further research is warranted to confirm the long-term effects of immunomodulatory therapies in patients with COVID-19.

SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study.

BACKGROUND: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. OBJECTIVE: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. METHODS: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. RESULTS: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). CONCLUSION: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.

SARS-CoV-2 (COVID-19) vaccination in dermatology patients on immunomodulatory and biologic agents: Recommendations from the Australasian Medical Dermatology Group.

As the phase III COVID-19 vaccine trials excluded patients on immunosuppressive treatments, or patients with significant autoimmunity, the Australasian Medical Dermatology Group make the following preliminary recommendations around COVID-19 vaccination in dermatology patients on immunomodulatory and/or biologic agents. Vaccination against COVID-19 is strongly encouraged for all patients on immunomodulatory drugs and/or biologic agents. There are currently insufficient data to recommend one COVID-19 vaccine or vaccine type (mRNA, recombinant, inactivated virus) over another. No specific additional risk in patients on immunomodulatory or biologic therapies has so far been identified. Data on vaccine efficacy in patients on immunomodulatory or biologic therapies are missing, so standard vaccination protocols are recommended until otherwise advised.

The most recent advances in understanding and managing hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, and debilitating skin disease of the hair follicle unit that typically develops after puberty. HS has a significant negative impact on both the quality of life (QOL) of patients affected by this disease as well as family members and caregivers. However, the pathogenesis of HS is multifactorial and still remains to be fully elucidated, which makes the development of treatments difficult. The last 10 years have seen a surge in HS research, and many new findings have come to light, yet much more remains to be elucidated. Physicians must employ a multidisciplinary approach to maximally address all facets of HS. Clinical characteristics of the disease that differ between females and males as well as across different races and ethnic groups must be considered. Targeted topical, oral, and injectable therapies continue to be developed for HS as a greater understanding of the pathogenesis is reached. However, randomized controlled trials regarding dietary factors that may contribute to HS are needed to meet our patients' growing concerns and questions about the role of diet in HS pathogenesis. Finally, improved outcome measures are needed to standardize HS severity and grading between physicians and clinical trials, and a more diverse representation of HS populations is needed in clinical trials.