COVID-19 Vaccine and Biologics: An Impending Dilemma.

The COVID-19 pandemic has forced healthcare providers across all specialties to adjust their methods of clinical practice. In Dermatology, focus on the continued safe usage of immunomodulating biologic therapies has attracted particular interest as the COVID-19 virus represents a novel infection risk. While guidance on biologic initiation and continuation has been established,1 the return to normalcy will likely involve a safe and effective vaccine. This vaccine(s) will represent a new clinical hurdle for prescribers who have continued patients on biologic therapy throughout the pandemic.

Multiple Evanescent White Dot Syndrome Following Medigen Vaccine Biologics Corporation COVID-19 Vaccination.

PURPOSE: To report a case of multiple evanescent white dot syndrome (MEWDS) following severe acute respiratory syndrome coronavirus 2 vaccination. STUDY DESIGN: Case report. RESULTS: A 36-year-old healthy Taiwanese female was presented with flashing lights in the right eye two days after the first dose of Medigen Vaccine Biologics Corporation (MVC) coronavirus disease 19 (COVID-19) vaccine. Examination of the retina revealed multiple white dots in the posterior pole extending to the mid-periphery. Disruption of ellipsoid zone on optical coherence tomography, early hyperfluorescence on fluorescein angiography, late hypo-cyanescence on indocyanine green angiography, and paracentral scotoma on visual field test were consistent with MEWDS. At four-week follow-up, the patient's fundus lesions resolved, and symptoms subsided without treatment. CONCLUSION: Resembling previous post-vaccine MEWDs cases, the symptoms are self-limited, and the visual prognosis is excellent. The presented case demonstrates MEWDS following MVC COVID-19 vaccine and suggests the immune-mediated basis for MEWDS in predisposed patients.

Biological therapies, asthma and coronavirus disease 2019.

PURPOSE OF REVIEW: As of June 2021, coronavirus disease 2019 (COVID-19) exceeded 180 million reported cases and was responsible for almost 4 million deaths globally. Asthma affects approximately 262 million people worldwide and is an important cause of morbidity and mortality. Presently, it appears asthma is neither associated with an increased risk of contracting COVID-19 nor with a risk of severe COVID-19 or COVID-19 related death. Regarding the severe asthma patients on biologics, questions remain. The purpose of this review is to discuss the evidence regarding the relationship between asthma, biologics and COVID-19. RECENT FINDINGS: The available evidence does not suggest that severe asthmatics on treatment with biologics have a higher risk of severe acute respiratory syndrome coronavirus 2 infection compared to the general population. It does not appear that they have a higher risk of severe disease or COVID-19 related death either. SUMMARY: This review suggests that treatment with biologics for severe asthma is safe and should be maintained during the COVID-19 pandemic. However, more studies are needed to address this question and the role of biological therapy on different asthma phenotypes.

Combination therapy with onasemnogene and risdiplam in spinal muscular atrophy type 1.

INTRODUCTION/AIMS: There are currently three medications approved for spinal muscular atrophy (SMA), but the use of these medications in combination has not been well described. METHODS: This is a retrospective report of four cases of SMA treated with dual onasemnogene and risdiplam therapy at our institution. RESULTS: Following onasemnogene therapy, all four patients experienced a perceived plateau of therapeutic benefit, at which time daily risdiplam was started. Transient fatigue and weakness was seen in two patients following risdiplam initiation, but this resolved within 1 mo. One patient was hospitalized with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and post-viral pneumonia, weeks following risdiplam initiation. No other adverse effects related to onasemnogene and risdiplam combination therapy were identified and all patients experienced objective and subjective improvement. DISCUSSION: Combination therapy with onasemnogene and risdiplam in patients with SMA appears to be well-tolerated. Further large prospective trials are needed to determine whether dual therapy is more efficacious than monotherapy, and to identify rare adverse events that may occur with the use of combination therapy.

Systemic Medications of Dermatological Importance in COVID-19.

Early December 2019 witnessed an international outbreak of a novel coronavirus (COVID 19) designated severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Since then, a number of therapeutic molecules have been explored to have potential efficacy against the SARS-Cov-2 per se or its sequelae. There are no Food and Drug Administration specific therapies approved so far; however, numerous drugs based on varying levels of evidence, in vitro studies and compassionate drug trials are being established as therapeutic agents, especially drugs approved for previous emergence of the severe acute respiratory syndrome (SARS-CoV-1) and Middle east respiratory syndrome coronavirus (MERS-Cov). Numerous active clinical trials for COVID-19 with more than 150 drugs and products are under study. Needless to say, many dermatological drugs are being employed to mitigate this pandemic threat. We aim to review drugs with potential against SARS-Cov-2 widely used in dermatology practice. Additionally, rampant and overzealous use of these drugs as well as introduction of new molecules might lead to emergence of adverse effects associated with these agents. Dermatologists must be on lookout for any cutaneous adverse effects of these drugs. J Drugs Dermatol. 2020;19(9):889-892. doi:10.36849/JDD.2020.5323.

Can we safely use systemic treatment in atopic dermatitis during the COVID-19 pandemic? Overview of selected conventional and biologic systemic therapies.

Introduction: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the medical community has faced major challenges that affect disease management in all areas. Dermatologists and immunologists have to choose appropriate treatment strategy taking into consideration the risk of infection and possible exacerbation of the course of the disease in patients with confirmed infection. Management of atopic dermatitis (AD) in moderate to severe cases is based on systemic therapy such as cyclosporine, azathioprine, methotrexate and dupilumab.Areas covered: A literature search in PubMed database was performed until 6 March 2021. In this review, the authors discuss non-biologic and biologic systemic medications for AD and provide an overview of therapeutic recommendations during COVID-19 pandemic.Expert opinion: In case of an active COVID-19 infection, conventional systemic treatment and biological treatment needs to be stopped until clinical recovery. Noninfected patients with systemic treatment of AD should continue their therapy via self-application. The authors can conclude that understanding of dupilumab therapy is better recognized in context AD treatment during COVID-19 pandemic in comparison to cyclosporine, azathioprine and methotrexate. However, this systemic immunosuppressants still require further investigation and literature complementation.

Oral inhalation for delivery of proteins and peptides to the lungs.

Oral inhalation is the preferred route for delivery of small molecules to the lungs, because high tissue levels can be achieved shortly after application. Biologics are mainly administered by intravenous injection but inhalation might be beneficial for the treatment of lung diseases (e.g. asthma). This review discusses biological and pharmaceutical challenges for delivery of biologics and describes promising candidates. Insufficient stability of the proteins during aerosolization and the biological environment of the lung are the main obstacles for pulmonary delivery of biologics. Novel nebulizers will improve delivery by inducing less shear stress and administration as dry powder appears suitable for delivery of biologics. Other promising strategies include pegylation and development of antibody fragments, while carrier-encapsulated systems currently play no major role in pulmonary delivery of biologics for lung disease. While development of various biologics has been halted or has shown little effects, AIR DNase, alpha1-proteinase inhibitor, recombinant neuraminidase, and heparin are currently being evaluated in phase III trials. Several biologics are being tested for the treatment of coronavirus disease (COVID)-19, and it is expected that these trials will lead to improvements in pulmonary delivery of biologics.

Safe handling and delivery of biological medications during the COVID-19 pandemic.

WHAT IS KNOWN AND OBJECTIVE: During the coronavirus disease of 2019 (COVID-19) pandemic, there were periods when patients were not able to collect their medications from the hospital. The purpose of this study is to report on our management of the handling and delivery of biological medications to patients during periods of lockdown in the Kingdom of Saudi Arabia (KSA). METHODS: A descriptive study conducted at our 380-bed tertiary care hospital. Managing the delivery of the biological medications was organized in six phases: (1) taskforce development, (2) identification of the relevant biological medications, (3) identification of patients, (4) organization of transportation, (5) medication delivery/pickup and (6) locating patients with unidentified addresses. The study was approved by our hospital's Institutional Review Board. RESULTS AND DISCUSSION: Biological medications were delivered to 1235/1373 (90%) patients. This included 1875/2036 (92%) prescriptions. 900 prescriptions were delivered to 570 patients living in 95 cities and villages across the kingdom. 141 patients received 183 prescribed oral biological medications and 477 patients received 787 prescribed parenteral biological medications delivered with temperature control. 224 parenteral biological medication were delivered by car to 116 patients living in less accessible cities in the west of the country. The car deliveries of parenteral biological medications required particularly careful handling, packaging and temperature control. Delivering biological medications to patients during the curfew was a unique experience. However, the approach we have used ensured safe access to medications under appropriate conditions. WHAT IS NEW AND CONCLUSION: Delivering biological medications to patients during the lockdown was challenging. With the possibility of a second wave of COVID-19, hospitals should have a standardized process in-place for delivering such medications.

Surfactant for the Treatment of ARDS in a Patient With COVID-19.

Patients with COVID-19 report severe respiratory symptoms consistent with ARDS. The clinical presentation of ARDS in COVID-19 is often atypical, as patients with COVID-19 exhibit a disproportionate hypoxemia compared with relatively preserved lung mechanics. This pattern is more similar to neonatal respiratory distress syndrome secondary to surfactant deficiency, which has been shown to benefit from exogenous surfactant. We present our experience with exogenous surfactant treatment in a patient with COVID-19 experiencing COVID-19-related ARDS. The patient responded with improved oxygenation, and we believe surfactant was the catalyst for the successful extubation and clinical improvement of the patient.

Understanding molecular mechanisms of biologics drug delivery and stability from NMR spectroscopy.

Protein therapeutics carry inherent limitations of membrane impermeability and structural instability, despite their predominant role in the modern pharmaceutical market. Effective formulations are needed to overcome physiological and physicochemical barriers, respectively, for improving bioavailability and stability. Knowledge of membrane affinity, cellular internalization, encapsulation, and release of drug-loaded carrier vehicles uncover the structural basis for designing and optimizing biopharmaceuticals with enhanced delivery efficiency and therapeutic efficacy. Understanding stabilizing and destabilizing interactions between protein drugs and formulation excipients provide fundamental mechanisms for ensuring the stability and quality of biological products. This article reviews the molecular studies of biologics using solution and solid-state NMR spectroscopy on structural attributes pivotal to drug delivery and stability. In-depth investigation of the structure-function relationship of drug delivery systems based on cell-penetrating peptides, lipid nanoparticles and polymeric colloidal, and biophysical and biochemical stability of peptide, protein, monoclonal antibody, and vaccine, as the integrative efforts on drug product design, will be elaborated.

Surfactant therapy for COVID-19 related ARDS: a retrospective case-control pilot study.

BACKGROUND: COVID-19 causes acute respiratory distress syndrome (ARDS) and depletes the lungs of surfactant, leading to prolonged mechanical ventilation and death. The feasibility and safety of surfactant delivery in COVID-19 ARDS patients have not been established. METHODS: We performed retrospective analyses of data from patients receiving off-label use of exogenous natural surfactant during the COVID-19 pandemic. Seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline, divided into five 30 ml aliquots) and delivered via a bronchoscope into second-generation bronchi. Patients were matched with 14 comparable subjects receiving supportive care for ARDS during the same time period. Feasibility and safety were examined as well as the duration of mechanical ventilation and mortality. RESULTS: Patients showed no evidence of acute decompensation following surfactant installation into minor bronchi. Cox regression showed a reduction of 28-days mortality within the surfactant group, though not significant. The surfactant did not increase the duration of ventilation, and health care providers did not convert to COVID-19 positive. CONCLUSIONS: Surfactant delivery through bronchoscopy at a dose of 720 mg in 150 ml normal saline is feasible and safe for COVID-19 ARDS patients and health care providers during the pandemic. Surfactant administration did not cause acute decompensation, may reduce mortality and mechanical ventilation duration in COVID-19 ARDS patients. This study supports the future performance of randomized clinical trials evaluating the efficacy of meticulous sub-bronchial lavage with surfactant as treatment for patients with COVID-19 ARDS.

Treatment Adherence and Clinical Outcomes of Patients with Inflammatory Bowel Disease on Biological Agents During the SARS-CoV-2 Pandemic.

BACKGROUND: The outbreak of COVID19 evolved rapidly into a global pandemic, forcing hospitals, including inflammatory bowel disease (IBD) referral units, to change their practices to ensure quality of care. AIMS: To describe the clinical outcomes and the fulfilment of the treatment schedule of patients with IBD treated with biological agents in a single-center of a red-zone of the pandemic, and to report the patients' perceptions about COVID-19 and the measures adopted at our center. METHODS: Therapeutic adherence and clinical outcomes were collected for all patients undergoing treatment with intravenous biologicals and subcutaneous biologicals at our center. A telephone survey was also performed to assess these patients' perceptions of the COVID pandemic and the related measures adopted at their IBD unit. RESULTS: A total of 234 patients were included (117 on intravenous and 117 on subcutaneous biologicals). Only 10% of patients postponed intravenous infusions intentionally and 5% postponed the collection of subcutaneous biologicals at the hospital pharmacy. Only five confirmed COVID-19 cases were registered (2.1%), all of them of mild severity. One hundred and fifty-five patients participated in the survey (77 on intravenous and 78 on subcutaneous drugs). Fear of going to the hospital was the most common reason for postponing biological administrations. Among those on combination therapy, only 7% admitted to have withdrawn immunosuppressants. CONCLUSIONS: Adherence to intravenous and subcutaneous biological therapies during the pandemic was high in a single-center cohort of IBD patients even though the cumulative incidence of confirmed COVID-19 was low.

Does therapy with biological drugs influence COVID-19 infection? Observational monocentric prevalence study on the clinical and epidemiological data of psoriatic patients treated with biological drugs or with topical drugs alone.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, there has been an open debate on the impact of biological drugs used in the treatment of psoriasis. To define whether patients under treatment with biologics suffer from increased morbidity and mortality from COVID-19, compared to psoriatic patients treated only with topical drugs, we designed an observational monocentric prevalence study recording the personal and clinical data of psoriatic patients, with focus on the presentation of signs and symptoms related to COVID-19 in the period of time ranging from 1 January 2020 to 31 May 2020. A total of 180 patients were enrolled into two groups: 100 patients in the topical therapy group and 80 patients in the biological therapy group. No statistically significant difference was found between the groups regarding the prevalence of COVID-19 infection and symptoms at a bivariable analysis with adjustment for confounders. In conclusion, psoriatic patients under treatment with biologics do not seem to be more susceptible to COVID-19 compared to other psoriatic patients and we suggest not interrupting treatment with biological drugs, even in areas suffering from active outbreaks of the disease.

Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review.

BACKGROUND: Based on current evidence, recent guidelines of the National Institute of Health, USA indicated the use of remdesivir and dexamethasone for the treatment of COVID-19 patients with mild-moderate disease, not requiring high-flow oxygen. No therapeutic agent directed against the immunologic pathogenic mechanisms related to the cytokine release syndrome complicating the disease was indicated. OBJECTIVES: The purpose of this review was to assess the clinical impact of different therapies for COVID-19; thus, helping to identify the optimal management of the disease. To explain the rationale for the different therapeutic approaches, the characteristics of SARS-CoV-2, the pathogenesis of COVID-19, and the immune response triggered by SARS-CoV-2 infection were reported. METHODS: The efficacy assessment of the different treatments was performed by a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Available English language published articles including randomised controlled trials, open-label trials of antivirals and immune therapies extracted from Medline, Google Scholar, and MedRxiv databases were analysed. For inclusion, the primary end point of the trials had to be the efficacy as measured by the improvement of clinical features, or mortality, or the Intensive Care Unit Admission rate, or the discharge number. Case reports, paediatric studies, and studies without control group were excluded. The literature search was extended up to August 15, 2020. RESULTS: After the removal of duplicate articles, and the exclusion of studies not meeting the eligibility criteria, 2 trials of lopinavir/ritonavir, 1 of favipiravir, 3 of remdesivir, 1 of dexamethasone, 3 of hydroxychloroquine, 2 of colchicine, 6 of tocilizumab, 1 of sarilumab, 1 of siltuximab, 2 of anakinra, 3 of baricitinib, 1 of ruxolitinib, 1 of mavrilimumab, and 1 of itolizumab were suitable for the review. Among antivirals, only remdesivir significantly reduced the time to recovery, and mortality. Data for chloroquine and hydroxychloroquine were largely inconclusive. In a large trial, dexamethasone 6 mg/day reduced mortality by one-third. Trials of tocilizumab and sarilumab did not definitively demonstrate efficacy. Anakinra significantly reduced the mortality in 2 trials. Three retrospective trials on a cumulative number of 145 patients, reported the efficacy of baricitinib, with significant reduction of intensive care unit admission, and deaths. These results were recently confirmed by the ACTT-2 trial. Due to paucity of studies and to the small size clinical series, the results of other immune therapies were not conclusive. CONCLUSIONS: Beyond the supportive therapy, up to now the best therapeutic approach for COVID-19 may be a three-step combination therapy, including remdesivir 100 mg/day (200 mg loading dose on first day) in the first stage of the disease, and combined dexamethasone 6 mg/day plus baricitinib 4 mg/day to target the immune dysregulation triggered by the SARS-CoV-2 infection. The promising results of anakinra should be confirmed by the ongoing RCTs.