Severe Respiratory Involvement Research Articles

Mycoplasma pneumoniae-associated severe autoimmune haemolytic anaemia in children: a case report from a resource limited setting

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia and respiratory tract infection in children. While traditionally known for its respiratory manifestations, extrapulmonary manifestations of Mycoplasma pneumoniae infections are rare, particularly autoimmune hemolytic anemia (AIHA). Emerging evidence suggests its association with AIHA in pediatric patients, especially with severe respiratory involvement. Here, we present a case of a child with cold AIHA secondary to Mycoplasma pneumoniae infection without marked pulmonary manifestations, from a resource limited setting, highlighting the importance of considering atypical presentations of this pathogen in pediatric patients. Understanding this association is crucial for timely diagnosis, appropriate management, and improved outcomes in affected children.

Advancing the Understanding of Vesicle-Associated Membrane Protein 1-Related Congenital Myasthenic Syndrome: Phenotypic Insights, Favorable Response to 3,4-Diaminopyridine, and Clinical Characterization of Five New Cases

BackgroundCongenital myasthenic syndromes (CMS) are a group of inherited neuromuscular junction (NMJ) disorders arising from gene variants encoding diverse NMJ proteins. Recently, the VAMP1 gene, responsible for encoding the vesicle-associated membrane protein 1 (VAMP1), has been associated with CMS. MethodsThis study presents a characterization of five new individuals with VAMP1-related CMS, providing insights into the phenotype. ResultsThe individuals with VAMP1-related CMS exhibited early disease onset, presenting symptoms prenatally or during the neonatal period, alongside severe respiratory involvement and feeding difficulties. Generalized weakness at birth was a common feature, and none of the individuals achieved independent walking ability. Notably, all cases exhibited scoliosis. The clinical course remained stable, without typical exacerbations seen in other CMS types. The response to anticholinesterase inhibitors and salbutamol was only partial, but the addition of 3,4-diaminopyridine (3,4-DAP) led to significant and substantial improvements, suggesting therapeutic benefits of 3,4-DAP for managing VAMP1-related CMS symptoms. Noteworthy is the identification of the VAMP1 (NM_014231.5): c.340delA; p.Ile114SerfsTer72 as a founder variant in the Iberian Peninsula and Latin America. ConclusionsThis study contributes valuable insights into VAMP1-related CMS, emphasizing their early onset, arthrogryposis, facial and generalized weakness, respiratory involvement, and feeding difficulties. Furthermore, the potential efficacy of 3,4-DAP as a useful therapeutic option warrants further exploration. The findings have implications for clinical management and genetic counseling in affected individuals. Additional research is necessary to elucidate the long-term outcomes of VAMP1-related CMS.

Analysing Pulmonary Effects of the COVID-19 and Treatment Methods

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has had a profound impact on global health. Among its various manifestations, respiratory effects have emerged as a critical aspect of the disease. This paper provides an overview of the respiratory complications associated with COVID-19, including acute respiratory distress syndrome (ARDS), pneumonia, and long-term lung sequelae. We delve into the pathophysiology of these effects, exploring the immune responses, cytokine storms, and vascular complications that contribute to respiratory compromise. Furthermore, we discuss the diagnostic methods, treatment strategies, and potential long-term implications for individuals recovering from severe respiratory involvement. A comprehensive understanding of the respiratory effects of COVID-19 is crucial for informing clinical management, public health policies, and ongoing research efforts.”

Ocular Manifestations among Hospitalized COVID-19 Patients in the Southeast of Iran

Background: COVID-19 has a range of manifestations among different patients. Knowing the various manifestations of COVID-19 could help in better managing the infection. This study aimed to investigate the ocular manifestations of hospitalized COVID-19 patients. Methods: In this study, 379 PCR-positive COVID-19 patients hospitalized in Afzalipour hospital, a tertiary care academic medical center in Kerman city, were recruited. Demographic variables (age and sex), history of systemic diseases (diabetes mellitus and arterial hypertension), systemic COVID-19 signs and symptoms (respiratory, gastrointestinal, neurologic, and sensory), and the severity of the disease were evaluated. Patients were asked about ophthalmic symptoms. If a patient had serious ocular complaints, such as ocular pain or vision loss, and needed specialized examination, an ophthalmologist examined the patient. Results: The patients’ mean (standard deviation) age was 54.2 (15.8) years. Overall, 46 patients (12.1%, 95% confidence interval: 9.0–15.8) showed at least one ocular manifestation. The most common signs and symptoms among those with ocular manifestations were redness (n=37, 80.4%), discharge (n=35, 76.1%), lacrimation (n=31, 67.4%), itching (n=15, 32.6%), and dry eye sensation (n=15, 32.6%). Ocular manifestations were more prevalent among those≥60 years old, those with hospitalization days>7 days, those with more severe respiratory system involvement, and diabetic patients. Conclusion: One out of eight COVID-19 inpatients showed at least one ocular manifestation. As tear and ocular secretions are considered a route for coronavirus transmission, it is essential to pay attention to the early detection of ocular manifestations.

1094. Comparison of Demographic and Clinical Characteristics in Survivors Vs. Decedents with Multisystem Inflammatory Syndrome in Children (MIS-C) During the COVID-19 Pandemic—CDC National Surveillance, February 2020-December 2022

Abstract Background Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe complication of SARS-CoV-2. Identifying clinical and demographic characteristics associated with MIS-C mortality and description of MIS-C decedents over time may help identify children at increased risk for poor outcomes and potentially inform treatment decisions. Methods This investigation included all MIS-C cases with known outcome reported to CDC MIS-C national surveillance from February 2020─December 2022. Clinical and demographic characteristics were compared between survivors and decedents. Decedents were described over time and classified by date of MIS-C illness onset into five pandemic waves corresponding to five peaks of MIS-C activity (Figure 1): (1) 2/19/2020─6/28/2020, (2) 6/29/2020─10/17/2020, (3) 10/18/2020─7/8/2021, (4) 7/9/2021─12/7/ 2021, and (5) 12/8/2021─12/31/2022. Waves 4 and 5 were periods of predominant Delta and Omicron SARS-CoV-2 variant circulation, respectively.Figure 1.Multisystem Inflammatory Syndrome in Children (MIS-C) Decedents by Pandemic MIS-C Wave, February 19, 2020-December 31, 2022, N=76 Results Seventy-six decedents and 8,691 survivors were reported (Table). A higher proportion of decedents compared with survivors were aged 16-20 years (41% vs 9%; p< 0.01), from the South (55% vs 41%; p=0.01) and had MIS-C illness onset in wave 1 (18% vs 7%; p< .01). Half (51%) of decedents had an underlying medical condition compared with 24% of survivors (p< 0.01). A higher proportion of decedents than survivors had severe cardiovascular (95% vs 76%), respiratory (99% vs 36%), renal (59% vs 19%), and neurologic (30% vs 4%) involvement, and fewer had mucocutaneous (33% vs 75%). Deaths in the 16-20 age group were predominant in waves 1-4 but comprised only 15% of deaths in wave 5, when 57% of decedents were aged 0-4 years (Figure 2). Race and ethnicity of decedents varied over time. Severe cardiovascular and respiratory involvement was high ( >85-100%) over time in decedents; other organ manifestations varied by MIS-C wave.Table.Demographic and Clinical Characteristics of Children with Multisystem Inflammatory Syndrome in Children (MIS-C)-CDC National Surveillance, February 2020-December 2022Figure 2.Demographic Characteristics and Organ Involvement of Children with Multisystem Inflammatory Syndrome in Children (MIS-C) Who Died Stratified by Pandemic MIS-C Wave, February 19, 2020-December 31, 2022, N=76 Conclusion Older age (16-20 years), residing in the South, illness early in the pandemic, underlying medical conditions, and severe organ involvement were all significantly associated with death among children with MIS-C. MIS-C decedent characteristics are dynamic and may continue to evolve with changes in underlying population immunity, SARS-CoV-2 transmission, and variant emergence. Disclosures All Authors: No reported disclosures

Nurses' experiences of critical care in the COVID-19 Intensive nursing unit

Background: The intensive care unit is one of the essential and vital departments of hospitals that accommodate patients in critical condition. Intensive care nurses play an important role in the evaluation, treatment, and management of these patients. The outbreak of the COVID-19 (Coronavirus disease ) pandemic, followed by severe respiratory involvement, highlighted the importance of nurses' performance in the intensive care unit. The aim of this study was to explain the nurses' experiences of nursing care in the COVID-19 intensive care unit.Methods: This study was qualitative content analysis. Participants were 12 nurses who were selected based on purposive sampling. Data collected by semi and unstructured interview. Data analysis was performed based on Graneheim and Lundman (2004) at three-phase. Research trustworthiness was confirmed by four criteria of credibility, transferability, dependability, and conformability.Results: In this study, a total of 1311 meaning units were extracted; after condensation and abstraction, 257 codes were obtained, which were extracted into 32 primary subcategories, eight secondary subcategories, and two themes. The first theme was nursing care inhibitors in the COVID-19 (Coronavirus disease) Intensive Care Unit included five categories: "Problems with personal protective equipment, lack of care supplies, Insufficient preparation of intensive care nurses, burnout of nurses, and care burden." The second theme was the strengths of nursing care in the intensive care unit in the COVID-19 included three categories: "Acquiring new knowledge and experience of intensive care, upgrading and developing the intensive care system and improving the image of nursing in the community."Conclusion: The COVID-19 pandemic was associated with challenges and problems for nursing and nursing care, the identification of which can help prepare for future crises. Also, due to its positive achievements for nursing, it can be used to improve the position of nursing and its care.

Sociodemographic and clinical characteristics of early COVID-19 deaths in Almadinah Almonawarah, Saudi Arabia: An analytical cross-sectional study.

Identification of clinical characteristics and risk factors for mortality in COVID-19 is important for early detection and precise case management. The study aimed to describe the sociodemographic, clinical, and laboratory characteristics of in-hospital COVID-19 deaths in Almadinah Almonawarah city, Saudi Arabia, and to identify risk factors for early mortality among them. This is an analytical cross-sectional study. The main outcomes were demographic and clinical characteristics of COVID 19 patients who died from March till December 2020, during the hospital stay. We collected 193 records of COVID-19 patients, from two major hospitals in Al Madinah region, Saudi Arabia. Descriptive and inferential analysis were performed to identify and relate the factors of early death. Out of the total deaths, 110 died during the first 14 days of admission (Early death group) and 83 died after 14 days of admission (Late death group). Early death group had a significantly higher percentages of old age patients (p=0.027) and males (72.7%). Comorbidities were found in 166 (86%) of cases. Multimorbidity were significantly higher in early deaths than in late deaths 74.5% (p=<0.001). Women had significantly higher mean values of CHA2SD2 comorbidity scores (3.28 versus 1.89 for men; p <0.001). Moreover, predictors of high comorbidity scores were older age (p=0.005), higher respiratory rate (p=0.035), and raised alanine transaminase (p=0.047). Old age, comorbid illness, and severe respiratory involvement were prevalent among COVID-19 deaths. Comorbidity scores were significantly higher in women. Comorbidity was found to be significantly more associated with early deaths.

Generation of an MTM1-mutant iPSC line (CRICKi008-A) from an individual with X-linked myotubular myopathy (XLMTM)

Centronuclear myopathies (CNMs) are a group of inherited rare muscle disorders characterised by the abnormal position of the nucleus in the center of the muscle fiber. One of CNM is the X-Linked Myotubular Myopathy, caused by mutations in the myotubularin (MTM1) gene (XLMTM), characterised by profound muscle hypotonia and weakness, severe bulbar and respiratory involvement. Here, we generated an induced pluripotent stem cell (iPSC) line from a patient with a severe form of XLMTM. Dermal fibroblasts were reprogrammed to pluripotency using a non-integrating mRNA-based protocol. This new MTM1-mutant iPSC line could facilitate disease-modelling and therapy development studies for XLMTM.

Comparison of T Lymphocyte Subsets and Natural Killer Lymphocytes in Moderate Versus Severe COVID-19 Patients.

Severe respiratory involvement that follows a process of immune dysregulation and intense cytokine production remains to be the most dreaded complication of Coronavirus Disease-2019 (COVID-19) infection. The aim of this study was to analyze T lymphocyte subsets and natural killer (NK) lymphocytes in moderate and severe cases of COVID-19 infection and assess their significance in disease severity and prognosis. Twenty moderate cases and 20 severe cases of COVID-19 were studied and compared regarding blood picture, biochemical markers, T lymphocyte population subsets, and NK lymphocytes, which were determined by flow cytometric analysis. On analyzing the flow cytometric data of T lymphocyte cells and their subsets and NK cells in two groups of COVID-19 infection (one group moderate and the other severe cases), some immature NK lymphocyte relative and absolute counts were higher in the severe patients with worse outcome and death, while some mature NK lymphocyte relative and absolute counts were depressed in both groups. Also, interleukin (IL)-6 was significantly higher in severe cases when compared to moderate cases, and there was a positive significant correlation between immature NK lymphocyte relative and absolute counts and IL-6. There was no statistically significant difference between T lymphocyte subsets (T helper and T cytotoxic) with disease severity or outcome. Some immature NK lymphocyte subsets contribute to the widespread inflammatory response that complicates severe cases of COVID-19; therapeutic approaches directed to enhancing NK maturation or drugs that block NK cell inhibitory receptors have a potential role in controlling COVID-19 induced cytokine storm.

Multisystem Inflammatory Syndrome in American Indian/Alaska Native Children, March 2020-May 2022.

We describe characteristics, clinical features and outcomes of multisystem inflammatory syndrome in children among American Indian and Alaska Native (AI/AN) persons compared with non-Hispanic white persons. AI/AN patients with multisystem inflammatory syndrome in children were younger, more often obese, and from areas of higher social vulnerability. A greater proportion of AI/AN patients had severe respiratory involvement and shock.

Gut microbiota composition in COVID-19 hospitalized patients with mild or severe symptoms.

Background and aimCOVID-19, the infectious disease caused by SARS-CoV-2 virus that has been causing a severe pandemic worldwide for more than 2 years, is characterized by a high heterogeneity of clinical presentations and evolution and, particularly, by a varying severity of respiratory involvement. This study aimed to analyze the diversity and taxonomic composition of the gut microbiota at hospital admission, in order to evaluate its association with COVID-19 outcome. In particular, the association between gut microbiota and a combination of several clinical covariates was analyzed in order to characterize the bacterial signature associate to mild or severe symptoms during the SARS-CoV-2 infection.Materials and methodsV3–V4 hypervariable region of 16S rRNA gene sequencing of 97 rectal swabs from a retrospective cohort of COVID-19 hospitalized patients was employed to study the gut microbiota composition. Patients were divided in two groups according to their outcome considering the respiratory supports they needed during hospital stay: (i) group “mild,” including 47 patients with a good prognosis and (ii) group “severe,” including 50 patients who experienced a more severe disease due to severe respiratory distress that required non-invasive or invasive ventilation. Identification of the clusters of bacterial population between patients with mild or severe outcome was assessed by PEnalized LOgistic Regression Analysis (PELORA).ResultsAlthough no changes for Chao1 and Shannon index were observed between the two groups a significant greater proportion of Campylobacterota and Actinobacteriota at phylum level was found in patients affected by SARS-CoV-2 infection who developed a more severe disease characterized by respiratory distress requiring invasive or non-invasive ventilation. Clusters have been identified with a useful early potential prognostic marker of the disease evolution.DiscussionMicroorganisms residing within the gut of the patients at hospital admission, were able to significantly discriminate the clinical evolution of COVID-19 patients, in particular who will develop mild or severe respiratory involvement. Our data show that patients affected by SARS-CoV-2 with mild or severe symptoms display different gut microbiota profiles which can be exploited as potential prognostic biomarkers paving also the way to new integrative therapeutic approaches.

Positive Aspects, Negative Aspects and Challenges Associated with Stem Cell Therapy for COVID - 19: A Mini-review.

Like any other pandemic, Covid-19 scenario has also demanded effective treatment options. The circumstances demand to utilize all the possible weapons in the armamentarium. There have been many issues regarding the short-term and long-term safety and efficacy of these options. Some options are like uncharted seas and these need a detailed and critical review with respect to safety, efficacy, feasibility and financial constraints. Mesenchymal stem cells (MSCs) therapy has been studied for many years for its potential role in diseases with complex pathogenesis. Its efficacy in controlling cytokine imbalance and immuno-modulatory properties is well proven. These effects are being extensively studied for potential extension of the benefits for an effective option for management of COVID-19 patients with severe respiratory involvement. In this mini-review, an attempt has been made to review positive aspects, negative aspects, and challenges influencing MSCs therapy in the management of COVID-19 disease. The results of various studies and literature reviews show that MSCs therapy can be considered as one of the potential options. This article reviews the role of Mesenchymal Stem Cell (MSC) transplantation in critically ill SARS-COV-19 patients with lung involvement. The MSCs counteract the cytokine storm, regulate the immune responses, facilitate the expression of essential growth factors, and eventually improve the local milieu and promote the restoration of pulmonary vascular and alveolar linings for early healing. As with all new therapeutic options, MSC therapy will also have to stand the test of time with respect to safety, specificity, and constraints like mass production and "available for all" at "affordable cost."

Development of a model for early differentiation of adenovirus pneumonia from Mycoplasma pneumoniae pneumonia.

Adenovirus pneumonia (AVP) and Mycoplasma pneumoniae pneumonia (MPP) have similar clinical manifestations such as a high prevalence of lung consolidation, making the differential diagnosis difficult before the etiology is reported. This study aimed to compare AVP and MPP, and to build a predictive model to differentiate them early. We selected 198 cases of AVP and 876 cases of MPP. Clinical manifestations, computed tomography (CT) features, and biomarkers were compared. A logistic regression model was built to predict AVP. The area under the curve (AUC) of the receiver-operating characteristic was calculated to evaluate the discriminant ability of the prediction model. Patients in the AVP group were mainly infants and toddlers, while the MPP group had more pre-school age children. The rate of hypoxemia and severe pneumonia was 3- and 11-times higher, respectively, in the AVP group than in the MPP group (5.6% vs. 1.8%, 27.8% vs. 2.5%, P<0.01). The proportion of patients with a Pediatric Logistic Organ Dysfunction-2 score ≥2 was 10 times higher in the AVP group than in the MPP group (17.4% vs. 1.7%, P<0.01). Bilateral pneumonia was present in 90.2% of the AVP group. Biomarkers, such as interleukin (IL)-2 receptor, IL-10 and lactic dehydrogenase (LDH), were considerably higher in the AVP group than in the MPP group (P<0.01). The predictive model included eight variables, namely: age, severe pneumonia, bilateral pneumonia, ground-glass attenuation, consolidation, atelectasis, C-reactive protein, and LDH. The AUC was 86.6%. Compared with MPP, AVP affects younger children, presents a more severe respiratory tract involvement, results in a larger range of lung lesions, and is associated with higher inflammatory biomarkers. Our predictive model includes a combination of clinical features, imaging findings, and biomarkers. It may help pediatricians in the early differentiation of AVP from MPP.

Autosomal dominant GDAP1 mutation with severe phenotype and respiratory involvement: A case report

Charcot Marie Tooth (CMT) is a heterogeneous group of genetic disorders characterized by progressive motor and sensory neuropathy. CMT is a multi-gene disorder with several possible mutations responsible for a wide range of clinical presentations. A specific mutation of the ganglioside-induced-differentiation-associated protein 1 (GDAP1) gene is associated with the axonal subtype of CMT (CMT2K) which is inherited in an autosomal dominant fashion, as well as the demyelinating subtype (CMT4A) which is inherited in an autosomal recessive pattern. Phenotypic disease expression is largely dependent on these inheritance patterns. While the autosomal recessive form (CMT4A) exhibits severe disease with an early onset, the autosomal dominant variant (CMT2K) tends to have milder phenotypes and a later onset. We describe an atypical presentation of a patient with severe CMT2K with rapidly progressive polyneuropathy, respiratory failure, and dysphonia. We suggest that this case will inspire further evaluation of disease heterogeneity and variants.

Characteristics and Outcomes of Cases of Children and Adolescents With Pediatric Inflammatory Multisystem Syndrome in a Tertiary Care Center in Mexico City.

BackgroundPediatric inflammatory multisystem syndrome (PIMS) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children that resembles Kawasaki syndrome and places them at high risk of cardiorespiratory instability and/or cardiac damage. This study aims to describe the clinical presentation and outcomes of patients with PIMS in Mexico City.MethodsThis was an observational study of children hospitalized for PIMS based on the Centers for Disease Control and Prevention case definition criteria, in a single tertiary care pediatric center in Mexico City between May 1, 2020, and September 30, 2021. Demographic characteristics, epidemiological data, medical history, laboratory tests, cardiologic evaluations, treatment, and clinical outcomes were analyzed.ResultsSeventy-five cases fulfilled the case definition criteria for PIMS [median age: 10.9 years, Interquartile range (IQR): 5.6–15.6]. Fifteen (20%) patients had a severe underlying disease, 48 (64%) were admitted to the intensive care unit, 33 (44%) required invasive mechanical ventilation and 39 (52%) received vasopressor support. The patients were clustered through latent class analysis based on identified symptoms: Cluster 1 had rash or gastrointestinal symptoms (n = 60) and cluster 2 were those with predominantly respiratory manifestations (n = 15). Two patients (2.7%) died, and both had severe underlying conditions. Five patients (6.7%), all from cluster 1, developed coronary aneurysms.ConclusionThere were a high proportion of patients with severe respiratory involvement and positive RT-PCR SARS-CoV-2 and very few cases of coronary aneurysms in our study which suggests that a high proportion of the children had severe acute COVID-19. The clinical manifestations and outcomes are comparable to previously reported international studies.

Liver and Gastrointestinal Involvement in Patients With COVID-19: A Retrospective Study

BackgroundCoronavirus disease 2019 (COVID-19) classically presents as a respiratory illness with fever, dry cough, and dyspnea on exertion. Along with respiratory signs and symptoms, gastrointestinal (GI) manifestations and liver injury have been recognized during the progression of the disease. This study aimed to determine the prevalence of GI symptoms and hepatic injury during COVID-19 infections and their consequences on the outcome of the disease.MethodologyWe conducted a retrospective survey of 715 participants age 16 or older diagnosed with COVID-19 and reported GI and hepatic manifestations in the Dammam Medical Complex in Dammam, Eastern Province, Saudi Arabia, from March 1, 2020, to May 31, 2020. We recorded clinical manifestations, laboratory test results, patient demographics, comorbidities, and treatments.ResultsThe mean age of the study population was 46 years (88% were male, 12% were female), and 80% were non-Saudi. While most patients recovered and were discharged (n=603, 84.62%), 100 (13.99%) died due to COVID-19. Type 2 diabetes was present in 182 patients (79%) discharged and 45 patients (21%) who died. Hypertension was present in 26 (67%) discharged and 158 patients (81%) who died. Cardiovascular disease was present in 26 patients (67%) discharged and 13 (33%) who died. Chronic kidney disease was found in 11 patients (61%) discharged and six (33%) who died. Diarrhea was present in 11% of patients, nausea in 8%, and vomiting in 9% of patients. Twenty percent of patients had at least one GI symptom. Only 10% of those who died had GI symptoms, while 88% of those discharged had GI symptoms. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, and γ-glutamyl transpeptidase were generally higher in the patients who died than in those who were discharged.ConclusionsWe noted an increase in at least one liver enzyme with no clinically significant acute liver injury or cases of acute liver failure as sequelae of COVID-19. However, the presence of injury at the time of admission resulted in a significantly higher mortality rate. Only a small number of patients infected with COVID-19 exhibited GI manifestations. The etiology of severe acute respiratory syndrome coronavirus 2-related GI involvement is due to multiple factors. It is not yet fully understood if GI manifestations are clinical signs of high viral loads or another physiological process. The clinical manifestation and laboratory test results indicate that COVID-19 impacts the hepatic system and GI tract, indicating that COVID-19 infection may risk liver and GI tract injury.

Muscle MRI characteristic pattern for late-onset TK2 deficiency diagnosis

Background and objectiveTK2 deficiency (TK2d) is a rare mitochondrial disorder that manifests predominantly as a progressive myopathy with a broad spectrum of severity and age of onset. The rate of progression is variable, and the prognosis is poor due to early and severe respiratory involvement. Early and accurate diagnosis is particularly important since a specific treatment is under development. This study aims to evaluate the diagnostic value of lower limb muscle MRI in adult patients with TK2d.MethodsWe studied a cohort of 45 genetically confirmed patients with mitochondrial myopathy (16 with mutations in TK2, 9 with mutations in other nuclear genes involved in mitochondrial DNA [mtDNA] synthesis or maintenance, 10 with single mtDNA deletions, and 10 with point mtDNA mutations) to analyze the imaging pattern of fat replacement in lower limb muscles. We compared the identified pattern in patients with TK2d with the MRI pattern of other non-mitochondrial genetic myopathies that share similar clinical characteristics.ResultsWe found a consistent lower limb muscle MRI pattern in patients with TK2d characterized by involvement of the gluteus maximus, gastrocnemius medialis, and sartorius muscles. The identified pattern in TK2 patients differs from the known radiological involvement of other resembling muscle dystrophies that share clinical features.ConclusionsBy analyzing the largest cohort of muscle MRI from patients with mitochondrial myopathies studied to date, we identified a characteristic and specific radiological pattern of muscle involvement in patients with TK2d that could be useful to speed up its diagnosis.

Impact of SARS-CoV-2 Infection Among Non-Invasive Ventilated ALS Patients

The impact of SARS-CoV-2 infection among neuromuscular diseases with respiratory involvement, including amyotrophic lateral sclerosis (ALS), is still to be elucidated. We aim to characterize the clinical outcome of ALS patients non-invasive ventilated (NIV), following SARS-CoV-2 infection. We analyzed retrospectively our patients followed regularly at our ALS clinic, from the beginning of the COVID-19 pandemic (middle March 2020) to March 2021. We included patients on NIV with a documented SARS-CoV-2 infection. We recorded demographic and clinical data, including from the acute infectious illness. Three men with spinal-onset ALS are described, mean age of onset was 55±9.1 years (45-61), and mean disease duration was 17.5±15.9 months (6.1-41). All of them were wheelchair-bounded, with a mean ALSFRS-R of 15.3±0.6 (15-16). One patient used NIV 15 hours/day, 2 between 4 to 7 hours/day, and all used assisted coughing twice daily. None had coexistent comorbidities. They were managed for SARS-CoV-2 infection as outpatients with fluticasone, bronchodilators, azithromycin and increasing frequency of assisted coughing. Supplemental oxygen (mean of 2 liters per minute) was needed in two patients, and one required NIV also during the daytime. Total recovery from SARS-CoV-2 infection was observed in all, despite being in an advanced stage of their disease, with severe respiratory involvement. Prompt medical treatment is recommended for ALS patients with severe disease infected by SARS-CoV-2.

Clinical and Histopathologic Features of Myocarditis in Multisystem Inflammatory Syndrome (Adult)–Associated COVID-19

Background:Multisystem inflammatory syndrome (MIS) associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a life-threatening condition first described in children (MIS-C). It is characterized by a hyperinflammatory state that involves the cardiovascular, gastrointestinal, dermatologic, and neurologic systems without severe respiratory system involvement. Myocarditis is one of the cardiovascular presentations of MIS that might be complicated with cardiogenic shock. There are few case reports describing SARS-CoV-2-related MIS in adults (MIS-A).Case Summary:Three cases of healthy young adults diagnosed with severe acute respiratory syndrome-CoV-2 related (MIS-A). The main presentation was cardiogenic shock secondary to histologically proven myocarditis, which resolved rapidly after initiation of medical therapy including anti-inflammatory and immunosuppressive drugs. All the cases, however, required mechanical circulatory support (MCS) as a bridge to recovery.CONCLUSIONS:It appears reasonable to treat the patient with fulminant myocarditis in SARS-CoV-2-associated MIS-A with high-dose corticosteroid “pulse” therapy in order to suppress the inflammatory response and MCS to correct initial metabolic derangement and reestablish/maintain vital organ perfusion. Addition of IV immunoglobulin and other immunomodulators should be assessed in a case-by-case basis especially considering the associated cost resource allocation.

Canine junctional epidermolysis bullosa due to a novel mutation in LAMA3 with severe upper respiratory involvement.

Junctional epidermolysis bullosa (JEB) is a group of congenital blistering skin diseases characterized by clefting through the lamina lucida of the basement membrane zone. To characterize the clinical and morphological features of a congenital mechanobullous disease in a litter of puppies with severe upper respiratory involvement, and to identify an associated genetic variant. Five of eight puppies in an Australian cattle dog cross-bred litter showed signs of skin fragility. Three were stillborn and one died at one month of age. The two surviving puppies were presented with blistering skin disease and severe respiratory distress. Additionally, one unaffected sibling was examined and blood was obtained for genetic testing. Post-mortem examination, histopathological evaluation and electron microscopy were performed. Whole genome sequencing (WGS) of one affected puppy was compared to a database of 522 dogs of 55 different breeds for variant analysis. Sanger sequencing of one additional affected and one unaffected sibling confirmed the variant. Clinically, severe mucocutaneous ulcers occurred in frictional areas with claw sloughing. Histopathological results revealed subepidermal clefts and electron microscopy confirmed the split in the lamina lucida. Post-mortem examination documented extensive pharyngeal and laryngeal lesions with granulation tissue and fibrinous exudate obscuring the airway. Moderate tracheal hypoplasia contributed. The WGS revealed a novel missense variant in the laminin α3-chain XP_537297.2p(Asp2867Val), with an autosomal recessive mode of inheritance. A novel variant in LAMA3 caused a generalized and severe phenotype of JEB with an unique clinical presentation of upper airway obstruction.