Treatment of Long-Haul COVID Patients With Off-Label Acyclovir.

The SARS-CoV-2 virus (COVID-19) became a global pandemic in March 2020. This novel, highly infectious virus caused millions of infections and deaths around the world. Currently, there are few medications that are available for the treatment of COVID-19. Those affected are most commonly given supportive care, with some experiencing symptoms for months. We report a series of four cases depicting the successful use of acyclovir in the treatment of the virus SARS-CoV-2 in patients with long-haul symptoms, especially those in the realm of encephalopathy and neurological problems. Treatment with acyclovir in these patients resolved their symptoms and lowered their IgG and IgM titers, supporting the use of acyclovir as a safe and effective treatment for COVID-19 neurologic symptoms. We suggest the use of the antiviral medication, acyclovir, as a treatment for patients with long-term symptoms and unusual presentations of the virus, such as encephalopathy or coagulopathy.

Comparative analysis of functional assay evidence use by ClinGen Variant Curation Expert Panels.

BACKGROUND: The 2015 American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) guidelines for clinical sequence variant interpretation state that "well-established" functional studies can be used as evidence in variant classification. These guidelines articulated key attributes of functional data, including that assays should reflect the biological environment and be analytically sound; however, details of how to evaluate these attributes were left to expert judgment. The Clinical Genome Resource (ClinGen) designates Variant Curation Expert Panels (VCEPs) in specific disease areas to make gene-centric specifications to the ACMG/AMP guidelines, including more specific definitions of appropriate functional assays. We set out to evaluate the existing VCEP guidelines for functional assays. METHODS: We evaluated the functional criteria (PS3/BS3) of six VCEPs (CDH1, Hearing Loss, Inherited Cardiomyopathy-MYH7, PAH, PTEN, RASopathy). We then established criteria for evaluating functional studies based on disease mechanism, general class of assay, and the characteristics of specific assay instances described in the primary literature. Using these criteria, we extensively curated assay instances cited by each VCEP in their pilot variant classification to analyze VCEP recommendations and their use in the interpretation of functional studies. RESULTS: Unsurprisingly, our analysis highlighted the breadth of VCEP-approved assays, reflecting the diversity of disease mechanisms among VCEPs. We also noted substantial variability between VCEPs in the method used to select these assays and in the approach used to specify strength modifications, as well as differences in suggested validation parameters. Importantly, we observed discrepancies between the parameters VCEPs specified as required for approved assay instances and the fulfillment of these requirements in the individual assays cited in pilot variant interpretation. CONCLUSIONS: Interpretation of the intricacies of functional assays often requires expert-level knowledge of the gene and disease, and current VCEP recommendations for functional assay evidence are a useful tool to improve the accessibility of functional data by providing a starting point for curators to identify approved functional assays and key metrics. However, our analysis suggests that further guidance is needed to standardize this process and ensure consistency in the application of functional evidence.

Prospective Assessment of Pill-Swallowing Ability in Pediatric Patients.

Difficulty with pill-swallowing ability (PSA) is common in children, yet formal evaluation is rare. The objective of this study was to prospectively evaluate and compare PSA of inpatient and outpatient children using the Pediatric Oral Medications Screener. We identified children aged 3 to 17 years admitted to a general or subspecialty pediatric service at a university hospital or outpatient clinic. Using the Pediatric Oral Medications Screener, patients were observed swallowing 3 different-sized placebo pills (5 mm tablet, 10 mm tablet, and 22 mm capsule), and subjective measures were assessed from parents and children. We analyzed 47 inpatients and 62 outpatients. Sixteen percent of patients could not swallow any pill, 11% only swallowed the small pill, 14% swallowed up to the medium pill, and 60% swallowed all formulations. After controlling for multiple factors, inpatients had superior PSA compared with outpatients ( P = .004). These results suggest targeted inpatient screening and widespread outpatient screening would likely identify children with reduced PSA.