atrophy – American ME and CFS Society

Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature review

Abstract:

The neurological complications of coronavirus disease 2019 (COVID-19) can range from simple tremors and dystonia to features of encephalopathy. Toll-like receptor 7 (TLR7) belongs to a family of innate immune receptors responsible for viral RNA detection (such as SARS-CoV-2) and immune response initiation. TLR7 loss of function variants have been previously reported as genetic risk factors for severe COVID-19 infection in young patients with no comorbidities.

In this case, we report a pediatric patient who developed severe long-term neurological deterioration following his COVID-19 infection. Presenting first to the clinic with episodic dystonia and finger spasticity, the patient’s condition rapidly deteriorated with a significant drop in the Glasgow Coma Scale (GCS). Despite improvement following initial treatment with rituximab and intravenous immunoglobulin, the patient’s symptoms relapsed, and GCS further dropped to 3/15.

Serial brain magnetic resonance imaging scans revealed diffuse parenchymal atrophy, ventricular enlargement, and spinal cord thickening. Autoimmune investigations were negative but clinical whole genome sequencing prioritized four gene variants, the most significant of which was a novel frameshift null variant of the X chromosomal TLR7 gene (c.1386_1389dup, p.[His464Ilefs*7]). This case illustrates a role for TLR7 in long-term COVID-19 complications and highlights that TLR7 deficiency in the future may be addressed as a therapeutic measure.

Source: Noor Eddin A, Al-Rimawi M, Peer-Zada F, Hundallah K, Alhashem A. Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature review. Front Neurol. 2023 Nov 29;14:1268035. doi: 10.3389/fneur.2023.1268035. PMID: 38093758; PMCID: PMC10716429. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10716429/ (Full text)

Sonographic Diaphragm Abnormalities are an Unexpectedly Frequent Feature of Long COVID Outpatients with Unexplained Dyspnea and Fatigue

Abstract:

Purpose: The primary aim of this study is to define the sonographic diaphragm phenotype of Long COVID rehabilitation outpatients with non-specific dyspnea and fatigue. We analyzed patients referred from a pulmonary post-COVID clinic that were lacking a specific cardiopulmonary diagnosis for their symptoms. Additionally, we report the functional outcomes of subset of patients who completed an outpatient cardiopulmonary physical therapy program.

Methods: This was a retrospective cohort study (n = 58) of consecutive patients referred for neuromuscular ultrasound assessment of diaphragm muscle using B-mode technique. Patients were recruited from a single academic hospital between February 25, 2021 and November 22, 2022.

Results: Sonographic abnormalities were identified in 57% (33/58) of patients, and in the vast majority of cases (33/33) was defined by a low diaphragm muscle thickness. Thinner diaphragm muscles are correlated with lower serum creatinine and creatine kinase values, but there was no association with markers of systemic inflammation. Thirty three patients participated in outpatient cardiopulmonary physical therapy that included respiratory muscle training, and 75.8% (25/33) had documented improvement.

Conclusion: In the outpatient rehabilitation setting, patients with Long COVID display low diaphragm muscle thickness, but intact muscle contractility, with surprising frequency on neuromuscular ultrasound. We speculate this represents a form of disuse atrophy. Also, these patients appear to have a favorable response to cardiopulmonary physical therapy that includes respiratory muscle training.

Source: Prabhav P. Deo, Joseph I. Bailey, Alexandra S. Jensen, Ellen Farr, Meghan Fahey, Matthew Isherwood, Keerthana Chakka, Lisa F. Wolfe, Ishan Roy, Marc A. Sala, Colin K. Franz. Sonographic Diaphragm Abnormalities are an Unexpectedly Frequent Feature of Long COVID Outpatients with Unexplained Dyspnea and Fatigue. medRxiv 2022.06.29.22277054; doi: https://doi.org/10.1101/2022.06.29.22277054 (Full text)