Early Treatment with Pegylated Interferon Lambda for Covid-19.

BACKGROUND: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. METHODS: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 µg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. RESULTS: A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Evaluation of a novel medical device for pegfilgrastim administration.

Pegfilgrastim, a pegylated form of granulocyte colony-stimulating factor, has reduced the risk of developing febrile neutropenia, which is associated with an increase in severe infection and prolonged hospitalization. However, pegfilgrastim administration requires that patients visit hospital following cancer chemotherapy, thus imposing a burden on patients and those around them. An on-body injector (OBI), which automatically administers pegfilgrastim about 27 hours after chemotherapy, was used in this study. The OBI, which consists of a main pump unit and infusion set, is a drug delivery device designed to be attached to the patient's body, with a timer-controlled dosing function. This study was conducted in breast cancer patients to evaluate the safety of pegfilgrastim administered subcutaneously via the OBI. The study period consisted of screening and treatment observation periods involving four cycles of neoadjuvant or adjuvant chemotherapy with docetaxel plus cyclophosphamide. One 3.6-mg pegfilgrastim dose was administered subcutaneously via OBI during each cycle of chemotherapy. The study enrolled 35 patients, and no serious adverse events or febrile neutropenia occurred. Administration of pegfilgrastim was successfully completed at all times when the OBI was attached to the patient, and no safety concerns associated with OBI function arose. For outpatients requiring pegfilgrastim following cancer chemotherapy, the use of an OBI was considered to be a safe option to reduce the need for outpatient visits that restrict their activities of daily living.

Successful Use of Certolizumab Pegol for Refractory Psoriatic Arthritis Triggered by COVID-19 Infection.

Recently, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread worldwide. Although nearly all patients incur mild-to-moderate disease from this viral infection, some develop severe manifestations with a poor prognosis. COVID-19 can also induce autoimmune disease; several cases of arthritis following COVID-19 have been documented in the literature, such as reactive arthritis and chronic arthritis. We herein report a case of psoriatic arthritis triggered by COVID-19. Although the arthritis had been refractory to glucocorticoids and methotrexate, certolizumab pegol subsequently led to remission.

Clinical Experience with Ropeginterferon Alfa-2b in the Off-Label Use for the Treatment of COVID-19 Patients in Taiwan.

INTRODUCTION: This study, for the first time to our knowledge, evaluated the efficacy of ropeginterferon alfa-2b, a long-acting pegylated interferon (IFN)-alfa, in the treatment of COVID-19. METHODS: We retrospectively evaluated ropeginterferon alfa-2b administered subcutaneously at a single dose of 250 µg for the treatment of mild and moderate COVID-19. Primary outcome was to compare the overall negative conversion time from the confirmed, last positive SARS-CoV-2 RT-PCR to the first RT-PCR negative conversion between patients receiving ropeginterferon alfa-2b plus standard of care (SOC) and those receiving SOC alone. RESULTS: Thirty-five patients with mild COVID-19 and 37 patients with moderate disease were included. Of them, 19 patients received SOC plus ropeginterferon alfa-2b and 53 patients received SOC alone. All patients with moderate disease in the ropeginterferon alfa-2b group showed RT-PCR negative conversion within 8 days, while a significant portion of patients in the SOC alone group failed to do so. For patients with moderate disease and age ≤ 65 years old, the ropeginterferon alfa-2b group had statistically significant shorter median RT-PCR conversion time than the SOC alone group (7 vs. 11.5 days, p < 0.05). CONCLUSIONS: Ropeginterferon alfa-2b showed the potential for the treatment of moderate COVID-19 patients. A randomized, controlled Phase III study is planned to further assess the effectiveness of ropeginterferon alfa-2b in COVID-19 patients.

Synthetic hydrogel nanoparticles for sepsis therapy.

Sepsis is a life-threatening condition caused by the extreme release of inflammatory mediators into the blood in response to infection (e.g., bacterial infection, COVID-19), resulting in the dysfunction of multiple organs. Currently, there is no direct treatment for sepsis. Here we report an abiotic hydrogel nanoparticle (HNP) as a potential therapeutic agent for late-stage sepsis. The HNP captures and neutralizes all variants of histones, a major inflammatory mediator released during sepsis. The highly optimized HNP has high capacity and long-term circulation capability for the selective sequestration and neutralization of histones. Intravenous injection of the HNP protects mice against a lethal dose of histones through the inhibition of platelet aggregation and migration into the lungs. In vivo administration in murine sepsis model mice results in near complete survival. These results establish the potential for synthetic, nonbiological polymer hydrogel sequestrants as a new intervention strategy for sepsis therapy and adds to our understanding of the importance of histones to this condition.

COVID-19 Vaccines in Children with Cow's Milk and Food Allergies.

The COVID-19 pandemic is the most challenging global health crisis of our times. Vaccination against COVID-19 plays a key role to control the current pandemic situation. The risk of allergic reactions to new COVID-19 vaccines is low. However, there is a debate on the safety in allergic patients following post marketing findings by different agencies. Our aim is to understand from current experiences whether children with cow's milk or food allergy are at higher risk than a general population for allergic reactions to COVID-19 vaccines. Current data indicate that patients with a history of allergy to cow's milk or other foods, even if severe, should receive COVID-19 vaccine in a setting with availability of treatments for anaphylactic reactions and under medical supervision. Recipients should be discharged after a protracted observation period of 30 min if no reaction developed.

Successful treatment of positive-sense RNA virus coinfection with autoimmune hepatitis using double filtration plasmapheresis.

Double filtration plasmapheresis (DFPP) is an apheretic technique that selectively removes high molecular weight substances using a plasma component filter. DFPP has been used to treat positive-sense RNA virus infections, mainly chronic hepatitis C virus (HCV) infection, because of its ability to directly eliminate viral particles from blood plasma from 2008 to about 2015, before direct-acting antiviral agents was marketed. This effect has been termed virus removal and eradication by DFPP. HCV is a positive-sense RNA virus similar to West Nile virus, dengue virus and the SARS and Middle East respiratory syndrome coronaviruses. SARS-CoV-2 is classified same viral species. These viruses are all classified in Family Flaviviridae which are family of single-stranded plus-stranded RNA viruses. Viral particles are 40-60 nm in diameter, enveloped and spherical in shape. We present a rare case of HCV removal where an RNA virus infection that copresented with virus-associated autoimmune hepatitis was eliminated using DFPP. Our results indicate that DFPP may facilitate prompt viraemia reduction and may have novel treatment applications for SARS-CoV-2, that is, use of therapeutic plasma exchange for fulminant COVID-19.

Efficacy and safety of pegylated interferon alfa-2b in moderate COVID-19: A phase II, randomized, controlled, open-label study.

OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alfa-2b (PEG IFN-α2b) along with the standard of care (SOC) in subjects with moderate COVID-19. METHODS: In this phase 2, randomized, open-label study, adult subjects aged ≥18 years with RT-PCR confirmed COVID-19 with moderate symptoms were randomized in a 1:1 to receive PEG IFN-α2b plus SOC, or SOC alone. The primary endpoint was improvement in clinical status on day 15, measured by the WHO 7-point ordinal scale. RESULTS: Forty subjects were randomized to PEG IFN-α2b plus SOC (n = 20) and SOC (n = 20). Overall, 19 (95.00%) subjects in PEG IFN-α2b plus SOC had achieved clinical improvement on day 15 compared to 13 (68.42%) subjects in SOC (p < 0.05). Overall, 80% and 95% of subjects in the PEG IFN-α2b plus SOC group had a negative RT-PCR result on day 7 and day 14, respectively, compared to 63% and 68% in the SOC group. Adverse events (AEs) were reported for eleven subjects in the PEG IFN-α2b plus SOC group and eight subjects in the SOC group. All reported AEs were mild. CONCLUSION: The significant improvement in clinical status on day 15 is likely due to faster viral reduction compared to SOC with the PEG IFN-α2b treated moderate COVID-19 subjects showing a difference as early as day seven and becoming significant by day 14.

Sterilizing Immunity against SARS-CoV-2 Infection in Mice by a Single-Shot and Lipid Amphiphile Imidazoquinoline TLR7/8 Agonist-Adjuvanted Recombinant Spike Protein Vaccine*.

The search for vaccines that protect from severe morbidity and mortality because of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19) is a race against the clock and the virus. Here we describe an amphiphilic imidazoquinoline (IMDQ-PEG-CHOL) TLR7/8 adjuvant, consisting of an imidazoquinoline conjugated to the chain end of a cholesterol-poly(ethylene glycol) macromolecular amphiphile. It is water-soluble and exhibits massive translocation to lymph nodes upon local administration through binding to albumin, affording localized innate immune activation and reduction in systemic inflammation. The adjuvanticity of IMDQ-PEG-CHOL was validated in a licensed vaccine setting (quadrivalent influenza vaccine) and an experimental trimeric recombinant SARS-CoV-2 spike protein vaccine, showing robust IgG2a and IgG1 antibody titers in mice that could neutralize viral infection in vitro and in vivo in a mouse model.

Cytokine storm intervention in the early stages of COVID-19 pneumonia.

Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.