Recombinant Human C1 Esterase Inhibitor for the Management of Adverse Events Related to Intravenous Immunoglobulin Infusion in Patients With Common Variable Immunodeficiency or Polyneuropathy: A Pilot Open-Label Study.

It has been hypothesized that low levels of C1 esterase inhibitor (C1-INH), a key inhibitor of the complement pathway, may play a role in the occurrence of adverse events (AEs) associated with intravenous immunoglobulin (IVIG) therapy. This open-label pilot study evaluated C1-INH replacement, with recombinant human C1-INH (rhC1-INH), as a potential therapy for adults requiring IVIG and experiencing AEs. Patients received two rounds of IVIG infusion [pre-treatment phase (no rhC1-INH), 4-8 weeks] and then three rounds of one dose of intravenous rhC1-INH 50 U/kg (maximum, 4,200 U) with subsequent IVIG infusion (treatment phase, 6-12 weeks). Nineteen adults completed the study; all had an autoimmune condition linked to common variable immunodeficiency (CVID) or polyneuropathy, and 57.9% had low baseline C1-INH levels. Mean ± SD total scores improved significantly with the Headache Impact Test (from 62.8 ± 6.2 at pre-treatment to 57.7 ± 9.1 after treatment; mean Δ, -5.0; p = 0.02) and Modified Fatigue Impact Scale (from 59.3 ± 13.1 to 51.2 ± 15.4; mean Δ, -8.1; p = 0.006). Significant improvements in the Migraine Disability Assessment were observed for three of five items (p ≤ 0.002). Mean ± SD C1-INH level increased from 26.8 ± 5.9 mg/dl after the second round of IVIG (pre-treatment) to 32.1 ± 7.8 mg/dl after the third rhC1-INH treatment; functional C1-INH levels increased from 115.8 ± 34.7% to 158.3 ± 46.8%. Future research is warranted to explore the benefit of C1-INH therapy for reduction of IVIG-related AEs, as well as the role of C1-INH in patients with CVID and autoimmune disease. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03576469.

Suspected Recurrent SARS-CoV-2 Infections Among Residents of a Skilled Nursing Facility During a Second COVID-19 Outbreak - Kentucky, July-November 2020.

Reinfection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is believed to be rare (1). Some level of immunity after SARS-CoV-2 infection is expected; however, the evidence regarding duration and level of protection is still emerging (2). The Kentucky Department for Public Health (KDPH) and a local health department conducted an investigation at a skilled nursing facility (SNF) that experienced a second COVID-19 outbreak in October 2020, 3 months after a first outbreak in July. Five residents received positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results during both outbreaks. During the first outbreak, three of the five patients were asymptomatic and two had mild symptoms that resolved before the second outbreak. Disease severity in the five residents during the second outbreak was worse than that during the first outbreak and included one death. Because test samples were not retained, phylogenetic strain comparison was not possible. However, interim period symptom resolution in the two symptomatic patients, at least four consecutive negative RT-PCR tests for all five patients before receiving a positive test result during the second outbreak, and the 3-month interval between the first and the second outbreaks, suggest the possibility that reinfection occurred. Maintaining physical distance, wearing face coverings or masks, and frequent hand hygiene are critical mitigation strategies necessary to prevent transmission of SARS-CoV-2 to SNF residents, a particularly vulnerable population at risk for poor COVID-19-associated outcomes.* Testing, containment strategies (isolation and quarantine), and vaccination of residents and health care personnel (HCP) are also essential components to protecting vulnerable residents. The findings of this study highlight the importance of maintaining public health mitigation and protection strategies that reduce transmission risk, even among persons with a history of COVID-19 infection.

Evaluation of Intravenous Immunoglobulin in Pediatric Acute-Onset Neuropsychiatric Syndrome.

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a clinical diagnosis in children who have an acute manifestation of varied neuropsychiatric symptoms, including obsessive compulsive disorder, eating disorders, tics, anxiety, irritability, and problems with attention/concentration. PANS may develop as a result of a postinfectious syndrome and may represent a new form of postinfectious autoimmunity. To test the hypothesis that multiple, consecutive infusions of intravenous immunoglobulin (IVIG) for PANS can be efficacious, a multisite, open-label study was designed. Methods: The primary endpoint was evaluation of the efficacy of IVIG [Octagam 5%] in PANS over a period of 6 months (six infusions) based on mean changes in psychological evaluation scores using 6 different assessments, including the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Clinical Global Impression of Severity, and the Parent-Rated Pediatric Acute Neuropsychiatric Symptom Scale (PANS Scale). Results: The final cohort consisted of 21 subjects (7 per site) with moderate to severe PANS. The mean age was 10.86 years (range: 4-16 years). Results demonstrated statistically significant reductions in symptoms from baseline to end of treatment in all six assessments measured. CY-BOCS results demonstrated statistically significant reductions in obsessive compulsive symptoms (p < 0.0001), resulting in >50% improvement sustained for at least 8 weeks after the final infusion and up to 46 weeks in a subset of subjects. Conclusions: In PANS, which may be associated with an underlying immune dysregulation, sequential infusions of IVIG [Octagam 5%] successfully ameliorated psychological symptoms and dysfunction, with sustained benefits for at least 8 weeks, and up to 46 weeks in a subset of subjects. In addition, baseline immune and autoimmune profiles demonstrated significant elevations in a majority of subjects, which requires further evaluation, characterization, and study to clarify the potential immune dysfunction by which PANS manifests and progresses.