Neurological Sequelae Research Articles

Characteristics and Impact of Long COVID at a Neurology Clinic

Introduction: Long COVID can also lead to neurological sequelae that affect existing diseases. This study explored how COVID-19 infection affects neurological patients and the relationship between long COVID and exacerbating factors. Methods: This retrospective study was conducted on 85 patients with neurological diseases after COVID-19 at the Neurology Department, Inje University Busan Paik Hospital, Korea. The data were collected between August and October 2022. The patients had a medical history, including COVID-19 infection, and completed symptom questionnaires. A long COVID questionnaire consisting of 35 inquiries in 10 categories was completed. Anxiety, depression, fatigue, functional difficulties, QOL, and health status changes were assessed. Results: The analysis comprised 85 participants (age: 56.4 ± 15.2 years; 63.5% women). Of the categories, neurological symptoms (68.2%) were the most prevalent, followed by systemic symptoms (64.7%) and cardiopulmonary symptoms (56.5%). Anxiety, depression, and fatigue symptoms were reported by 36.5%, 34.1%, and 42.4% of the participants. Subjective neurological deterioration after COVID-19 was reported in 28 participants (28/81, 34.6%). Anxiety, depression, and fatigue were influenced by long COVID symptoms and the subjective deterioration of neurological conditions. Conclusion: This study analyzed the long COVID symptoms in patients with preexisting neurological conditions and their impact on mental health and quality of life. One-third of the participants reported a subjective worsening of their preexisting neurological conditions. This study highlights the need for comprehensive follow-ups and a multidisciplinary approach for patients with neurological conditions and prolonged COVID-19 symptoms.

Exploring the Potential Long-term Impact of SARS-CoV-2 on Protein Misfolding and Amyloid-related Conditions.

The long-term impact of the COVID-19 pandemic concerns risk to human health, particularly its potential association with protein misfolding and amyloidosis. This review article explores the causality relationship between SARS-CoV-2 infection, and protein misfolding, leading to amyloid-related conditions. It delves into the mechanisms by which viral proteins may accelerate amyloid formation, exacerbating post-infection complications, including neurological sequelae. Drawing from interdisciplinary research and clinical observations, the potential links between COVID-19, vaccination, and amyloidosis, emphasize the importance of understanding the longterm effect of post-COVID symptoms. This review examines the potential role of COVID-19-related proteins in the formation of amyloid in other related proteins of amyloidosis.

Evaluation of end-organ protection in newborns and infants after surgery of aortic arch hypoplasia: A prospective randomized study.

Surgical repair of aortic arch hypoplasia in children requires a "dry" surgical field with reliable end-organ protection. Perfusion strategies commonly involve deep hypothermic circulatory arrest (DHCA) and variations of the continuous perfusion techniques, such as selective antegrade cerebral perfusion (SACP) and full-flow perfusion with double aortic cannulation (DAC). We aimed to evaluate the end-organ protection in the surgery of aortic arch hypoplasia in newborns and infants using DHCA and DAC. 66 newborns and infants with aortic arch hypoplasia and biventricular anatomy were enrolled in this prospective study. Patients were randomly assigned into two groups according to the perfusion strategy - DHCA (n = 33); and DAC (n = 33). Primary endpoint: acute kidney injury (AKI), graded according to the KDIGO score. Secondary endpoints: neurological sequelae (pre- and postoperative MRI), in-hospital mortality. The lowest temperature was 32 (28; 34)°С in the DAC group and 23 (20; 25)°С in the DHCA group. The patients with DAC had lower incidence of AKI (6 patients (18.2%) versus 19 patients (57.6%); p = .017). In the multivariate analysis, the inotropic index at 48h was identified as a risk factor, increasing the risk of AKI by 4%. The DHCA group was associated with a 3.8-fold increase in the risk of AKI. There was no difference in hospital mortality between the DAC and DHCA groups (1 patient (3%) versus 3 patients (9.1%); p = .61). Neurological sequelae by MRI scan were observed in 18 patients (54.5%) in the DHCA group compared to 5 patients (15.15%) in the DAC group (p = .026). The only risk factor identified in the multivariate analysis for neurological lesions on MRI scan was the DHCA group, which increased the risk by 8.8 times. Surgical reconstruction of the aortic arch hypoplasia using the method of full-body perfusion reduces the incidence of neurological lesions and renal complications requiring renal replacement therapy compared with the deep hypothermic circulatory arrest in neonates and infants.

BNIP3-mediated mitophagy attenuates hypoxic-ischemic brain damage in neonatal rats by inhibiting ferroptosis through P62-KEAP1-NRF2 pathway activation to maintain iron and redox homeostasis.

As a major contributor to neonatal death and neurological sequelae, hypoxic-ischemic encephalopathy (HIE) lacks a viable medication for treatment. Oxidative stress induced by hypoxic-ischemic brain damage (HIBD) predisposes neurons to ferroptosis due to the fact that neonates accumulate high levels of polyunsaturated fatty acids for their brain developmental needs but their antioxidant capacity is immature. Ferroptosis is a form of cell death caused by excessive accumulation of iron-dependent lipid peroxidation and is closely associated with mitochondria. Mitophagy is a type of mitochondrial quality control mechanism that degrades damaged mitochondria and maintains cellular homeostasis. In this study we employed mitophagy agonists and inhibitors to explore the mechanisms by which mitophagy exerted ferroptosis resistance in a neonatal rat HIE model. Seven-days-old neonatal rats were subjected to ligation of the right common carotid artery, followed by exposure to hypoxia for 2 h. The neonatal rats were treated with a mitophagy activator Tat-SPK2 peptide (0.5, 1 mg/kg, i.p.) 1 h before hypoxia, or in combination with mitochondrial division inhibitor-1 (Mdivi-1, 20 mg/kg, i.p.), and ferroptosis inhibitor Ferrostatin-1 (Fer-1) (2 mg/kg, i.p.) at the end of the hypoxia period. The regulation of ferroptosis by mitophagy was also investigated in primary cortical neurons or PC12 cells in vitro subjected to 4 or 6 h of OGD followed by 24 h of reperfusion. We showed that HIBD induced mitochondrial damage, ROS overproduction, intracellular iron accumulation, lipid peroxidation and ferroptosis, which were significantly reduced by the pretreatment with Tat-SPK2 peptide, and aggravated by the treatment with Mdivi-1 or BNIP3 knockdown. Ferroptosis inhibitors Fer-1 and deferoxamine B (DFO) reversed the accumulation of iron and lipid peroxides caused by Mdivi-1, hence reducing ferroptosis triggered by HI. We demonstrated that Tat-SPK2 peptide-activated BNIP3-mediated mitophagy did not alleviate neuronal ferroptosis through the GPX4-GSH pathway. BNIP3-mediated mitophagy drove the P62-KEAP1-NRF2 pathway, which conferred ferroptosis resistance by maintaining iron and redox homeostasis via the regulation of FTH1, HO-1, and DHODH/FSP1-CoQ10-NADH. This study may provide a new perspective and a therapeutic drug for the treatment of neonatal HIE.

Chronic subdural hematoma that may be caused by nephrotic syndrome: a case report and literature review.

Chronic subdural hematoma (CSDH) is a common complication of neurosurgery. Craniocerebral trauma is the likely cause. There are no reports relating CSDH with nephrotic syndrome. Its pathogenesis is very rare, and there are no previous reports on treatments for this disease. We report a case of chronic subdural hematoma that may be caused by nephrotic syndrome and review the previous literature on this subject. We report a rare case of chronic subdural hematoma that may be caused by nephrotic syndrome. After the patient was admitted to the hospital, relevant laboratory tests were conducted, and a large amount of protein was detected in the patient's urine, indicating hypoproteinaemia and hyperlipidemia. The patient was diagnosed with nephrotic syndrome. After the exclusion of related surgical contraindications, the patient underwent trepanation and drainage of the chronic subdural hematoma. Subsequent treatment with oral atorvastatin was provided after surgery. The patient was transferred to the nephrology department for further treatment of nephrotic syndrome if his neurological condition improved. No neurological sequelae were detected at the follow-up visit 3 months after the operation. Chronic subdural hematomas are rarely caused by nephrotic syndrome. Trepanation and drainage may be considered for patients confirmed to have adequate hematoma liquefaction on imaging and who can tolerate craniotomy. Atorvastatin should be supplemented as prophylactic treatment after the operation. Nephrotic syndrome should be treated as soon as the patient's neurological condition is stable.

The DERIVO2 Heal Embolization Device in the Treatment of Ruptured and Unruptured Intracranial Aneurysms: aRetrospective Multicenter Study.

The use of flow diverting stents in the treatment of intracranial aneurysms is associated with arisk of neurological morbidity due to their thrombogenicity. To reduce this risk different surface modifications have been developed. The Derivo2 Embolization Device (Acandis, Pforzheim, Germany) has proven to be asafe and effective flow diverter. To overcome the risk of thrombo-embolism, the device was modified by adding an anti-thrombogenic fibrin-heparin coating. We aimed to assess the safety and effectiveness of the Derivo2 heal Embolization Device. Retrospective multicenter data from nine German neurovascular centers between February 2022 until December 2023 were used. Patients treated with the Derivo2 heal Embolization Device for unruptured or ruptured intracranial aneurysms were included. Peri- and postprocedural adverse events, clinical outcomes, and angiographic follow-up results were evaluated. 84patients (73.8% female; mean age58.7 years) with 89aneurysms (mean size 9.8 mm) were included. 87.6% were located in the anterior circulation. Most of them were sidewall aneurysms (88.8%). 96flow diverters were used. 99.0% were successfully implanted. An in-stent balloon angioplasty was performed in 6.0% of the cases. An additional coiling was performed in 28.6%. Technical difficulties were present in 12.0% of the cases. Thrombotic events occurred in 4.8% with no neurological sequelae. Mortality and morbidity were 0 and 1.2% respectively. Adequate aneurysm occlusion was achieved in 80.7% with amean follow-up time of 6.6months. The Derivo2 heal Embolization Device showed asatisfying aneurysm occlusion and safety with alow rate of neurological morbidity.

Neuropsychological outcomes of patients with haematological malignancies undergoing chimeric antigen receptor T-cell therapy: protocol for a prospective study

IntroductionImmune effector cell-associated neurotoxicity syndrome (ICANS) is a common side-effect of chimeric antigen receptor T-cell (CAR-T) therapy, with symptoms ranging from mild to occasionally life-threatening. The neurological, cognitive, psychiatric and...

Machine learning-causal inference based on multi-omics data reveals the association of altered gut bacteria and bile acid metabolism with neonatal jaundice

ABSTRACT Early identification of neonatal jaundice (NJ) appears to be essential to avoid bilirubin encephalopathy and neurological sequelae. The interaction between gut microbiota and metabolites plays an important role in early life. It is unclear whether the composition of the gut microbiota and metabolites can be used as an early indicator of NJ or to aid clinical decision-making. This study involved a total of 196 neonates and conducted two rounds of “discovery-validation” research on the gut microbiome-metabolome. It utilized methods of machine learning, causal inference, and clinical prediction model evaluation to assess the significance of gut microbiota and metabolites in classifying neonatal jaundice (NJ), as well as the potential causal relationships between corresponding clinical variables and NJ. In the discovery stage, NJ-associated gut microbiota, network modules, and metabolite composition were identified by gut microbiome-metabolome association analysis. The NJ-associated gut microbiota was closely related to bile acid metabolites. By Lasso machine learning assessment, we found that the gut bacteria were associated with abnormal bile acid metabolism. The machine learning-causal inference approach revealed that gut bacteria affected serum total bilirubin and NJ by influencing bile acid metabolism. NJ-associated gut bile acids are potential biomarkers of NJ, and clinical prediction models constructed based on these biomarkers have some clinical effects and the model may be used for disease risk prediction. In the validation stage, it was found that intestinal metabolites can predict NJ, and the machine learning-causal inference approach revealed that bile acid metabolites affected NJ itself by affecting the total bilirubin content. Intestinal bile acid metabolites are potential biomarkers of NJ. By applying machine learning-causal inference methods to gut microbiome-metabolome association studies, we found NJ-associated intestinal bacteria and their network modules and bile acid metabolite composition. The important role of intestinal bacteria and bile acid metabolites in NJ was determined, which can predict the risk of NJ.

Imaging panorama of pediatric central nervous system tuberculosis.

Central nervous system tuberculosis (CNS TB) is the most dreaded manifestation of systemic tuberculosis in the pediatric age group. It is associated with high morbidity and mortality due to severe neurological complications and sequelae. Knowledge about the imaging spectrum of CNS TB will help in early presumptive diagnosis and prompt treatment, reducing the development of complications. Imaging also plays a vital role in monitoring the progression of disease after the initiation of antituberculosis therapy. Advanced magnetic resonance imaging (MRI) techniques have recently improved the diagnostic efficacy manifold.In this review, we describe the imaging characteristics, the role of advanced imaging techniques, and follow-up imaging in various types of CNS TB in the pediatric population.

Neurological Impact of Respiratory Viruses: Insights into Glial Cell Responses in the Central Nervous System.

Respiratory viral infections pose a significant public health threat, particularly in children and older adults, with high mortality rates. Some of these pathogens are the human respiratory syncytial virus (hRSV), severe acute respiratory coronavirus-2 (SARS-CoV-2), influenza viruses (IV), human parvovirus B19 (B19V), and human bocavirus 1 (HBoV1). These viruses cause various respiratory symptoms, including cough, fever, bronchiolitis, and pneumonia. Notably, these viruses can also impact the central nervous system (CNS), leading to acute manifestations such as seizures, encephalopathies, encephalitis, neurological sequelae, and long-term complications. The precise mechanisms by which these viruses affect the CNS are not fully understood. Glial cells, specifically microglia and astrocytes within the CNS, play pivotal roles in maintaining brain homeostasis and regulating immune responses. Exploring how these cells interact with viral pathogens, such as hRSV, SARS-CoV-2, IVs, B19V, and HBoV1, offers crucial insights into the significant impact of respiratory viruses on the CNS. This review article examines hRSV, SARS-CoV-2, IV, B19V, and HBoV1 interactions with microglia and astrocytes, shedding light on potential neurological consequences.

FERN: is it possible to conduct a randomised controlled trial of intervention or expectant management for early-onset selective fetal growth restriction in monochorionic twin pregnancy – protocol for a prospective multicentre mixed-methods feasibility study

IntroductionSelective fetal growth restriction (sFGR) in monochorionic twin pregnancy, defined as an estimated fetal weight (EFW) of one twin <10th centile and EFW discordance ≥25%, is associated with stillbirth and...

Long-term Health Outcomes After Hospital Discharge Among Children Hospitalized for MIS-C or COVID-19, September 29, 2021, to June 21, 2022.

The long-term effects of children hospitalized with multisystem inflammatory syndrome in children (MIS-C) or acute COVID-19 are not well known. Our objective was to determine long-term outcomes. Children hospitalized with MIS-C or COVID-19 at 3 US hospitals from March 2020, through February 2021 were followed to assess health through 2 years post-hospitalization using medical records and patient surveys. Medical record abstraction was performed for 183 patients hospitalized with MIS-C, 53 of whom participated in surveys, and 97 patients hospitalized with COVID-19, 35 of whom participated in surveys. Patients with MIS-C were younger (median, 9 vs. 14 years of age for COVID-19 patients; P = 0.004), more frequently male (62% vs. 39%; P < 0.001) and had more cardiac (14% vs. 2%; P = 0.001) and neurologic sequelae (8% vs. 1%; P = 0.023). Children with COVID-19 more often had other comorbidities (59% vs. 19%; P < 0.001). Full mental recovery at the time of survey 2 (median, 16 months post-hospitalization for patients with MIS-C and 20 months for patients with COVID-19) was 85% and 88%, respectively; full physical recovery was 87% and 81%, respectively; and nearly all had resumption of normal activities. Patients with MIS-C reported more frequent headache at 1 month (45% vs. 20%; P = 0.037). Patients with COVID-19 were more likely to report cough at 1 month (37% vs. 17%; P = 0.045). Fatigue persisted >1 year in 15%-20% of patients in both groups. Approximately 20% of children with MIS-C and COVID-19 continued to have symptoms including fatigue and headache >1 year after hospital discharge. The duration of these findings emphasizes the importance of providers following patients until sequelae have resolved.

Central Nervous System Disorders of Marine Mammals: Models for Human Disease?

This article deals with Central Nervous System (CNS) disorders of marine mammals as putative neuropathology and neuropathogenesis models for their human and, to some extent, their animal "counterparts" in a dual "One Health" and "Translational Medicine" perspective. Within this challenging context, special emphasis is placed upon Alzheimer's disease (AD), provided that AD-like pathological changes have been reported in the brain tissue of stranded cetacean specimens belonging to different Odontocete species. Further examples of potential comparative pathology interest are represented by viral infections and, in particular, by "Subacute Sclerosing Panencephalitis" (SSPE), a rare neurologic sequela in patients infected with Measles virus (MeV). Indeed, Cetacean morbillivirus (CeMV)-infected striped dolphins (Stenella coeruleoalba) may also develop a "brain-only" form of CeMV infection, sharing neuropathological similarities with SSPE. Within this framework, the global threat of the A(H5N1) avian influenza virus is another major concern issue, with a severe meningoencephalitis occurring in affected pinnipeds and cetaceans, similarly to what is seen in human beings. Finally, the role of Brucella ceti-infected, neurobrucellosis-affected cetaceans as putative neuropathology and neuropathogenesis models for their human disease counterparts is also analyzed and discussed. Notwithstanding the above, much more work is needed before drawing the conclusion marine mammal CNS disorders mirror their human "analogues".

A Study of Neurological Involvement in Dengue and Chikungunya Infection.

Chikungunya virus (CHIKV) and dengue fever have been reported for recent epidemics worldwide, with varied clinical involvement. Chikungunya was first reported to affect the nervous system in the 1960s. The clinical profile of dengue with multi-organ involvement is varied with reported involvement of the central nervous system in some. The aim of this study was to study the frequency and pattern of neurological involvement in patients admitted with dengue and chikungunya in a tertiary care hospital. Patients admitted with confirmed chikungunya and dengue were evaluated clinically and investigations were enrolled in the study. Patients with preexisting neurological issues, obvious metabolic, vascular, or septic causes for neurological involvement were excluded from the study. A total of 309 patients with chikungunya were included in the study. Out of these, 11 (3.56%) patients were found to have neurological involvement. The most common presentations were altered sensorium (100%) followed by headache (81.81%). The relative risk of mortality in patients with neurological involvement due to chikungunya was 7.96. A total of 443 patients with dengue fever were enrolled in the study. Out of these, 5 (1.10%) patients were found to have neurological involvement. The most common presentations were altered sensorium and headache (100%), followed by vomiting (80%). The relative risk of mortality in patients with neurological involvement due to dengue was 5.15. The recent epidemic of chikungunya and dengue virus infections was associated with various neurological complications. Neurological involvement of chikungunya and dengue was identified to be a bad prognostic factor with significantly higher mortality. This is a single center study, involving only the patients admitted to the hospital. Furthermore, being an observational study, follow-up could not be done to look for neurological sequelae.

Preclinical Assessment of a Cannabinoid CB2 Receptor Antagonist in a Murine Model of Cerebral Malaria

Malaria is a most important parasitic disease due to its highest impact worldwide. It results in around 200 million clinical cases and 0,5-1 million deaths per year, mainly due to cerebral malaria (CM), a life-threatening neurological syndrome that predominantly affects predominantly children under five years old. CM follows neurological alterations leading to the death if left untreated, and, even when it is treated, it is fatal in 15-20% of cases. Moreover, among the survivors, more than 10% of the children develop neurological sequelae. Consequently, there is an urgent need to find therapies to attenuate these neurological signs. Recent evidence has proposed the endocannabinoid system, which plays an important neuromodulatory function in the central nervous system (CNS), also including immunomodulation preferentially exerted by CB2 receptor. Previous studies have shown that the genetic ablation of this receptor improved mice survival against CM, suggesting a potential for the pharmacological treatment of CM with selective antagonists of this receptor. Considering this background, we investigated CM therapy by a classic CB2 antagonist SR144528 in a murine model of the disease. First, we carried out binding studies with SR144528 to confirm its pharmacodynamic profile (binding affinity [Ki] value = 2.34 ± 0.61 nM; and efficacy [IC50] = 96.17 ± 1.41 nM, at the CB2 receptor). Second, P. berghei ANKA infected C57BL/6 mice were treated daily with SR144528 and assessed for parasitemia growth and neurological alterations. 30% of the treated mice showed partial recovery of CM symptoms with 20% increased survival, but finally succumbing to hyperparasitemia and severe anemia. These preliminary preclinical results suggest that, although part of the CM course might be modulated by the pharmacological blockade of the CB2 receptor, other elements trigger the lethal outcome. Thus, while our hypothesis could not be completely validated in this CM model, we detail here all obtained results for further research.

An integrated bioinformatics approach reveals the potential role of microRNA-30b-5p and let-7a-5p during SARS CoV-2 spike-1 mediated neuroinflammation

SARS-CoV-2 induced neuroinflammation contributing to neurological sequelae is one of the critical outcomes of long-COVID, however underlying regulatory mechanisms involved therein are poorly understood. We deciphered the profile of dysregulated microRNAs, their targets, associated pathways, protein–protein interactions (PPI), transcription factor-hub genes interaction networks, hub genes–microRNA co-regulatory networks in SARS-CoV-2 Spike-1 (S1) stimulated microglial cells along with candidate drug prediction using RNA-sequencing and multiple bioinformatics approaches. We identified 11 dysregulated microRNAs in the S1-stimulated microglial cells (p < 0.05). KEGG analysis revealed involvement of important neuroinflammatory pathways such as MAPK signalling, PI3K-AKT signalling, Ras signalling and axon guidance. PPI analysis further identified 11 hub genes involved in these pathways. Real time PCR validation confirmed a significant upregulation of microRNA-30b-5p and let-7a-5p; proinflammatory cytokines- IL-6, TNF-α, IL-1β, GM-CSF; and inflammatory genes- PIK3CA and AKT in the S1-stimulated microglial cells, while PTEN and SHIP1 expression was decreased as compared to the non-stimulated cells. Drug prediction analysis further indicated resveratrol, diclofenac and rapamycin as the potential drugs based on their degree of interaction with hub genes. Thus, targeting of these microRNAs and/or their intermediate signalling molecules would be a prospective immunotherapeutic approach in alleviating SARS-CoV-2-S1 mediated neuroinflammation; and needs further investigations.

Identification of the risk factors for insomnia in nurses with long COVID-19

PurposeTo investigate the prevalence of insomnia among nurses with long COVID-19, analyze the potential risk factors and establish a nomogram model.MethodsNurses in Ningbo, China, were recruited for this study. General demographic information and insomnia, burnout, and stress assessment scores were collected through a face-to face questionnaire survey administered at a single center from March to May 2023. We used LASSO regression to identify potential factors contributing to insomnia. Then, a nomogram was plotted based on the model chosen to visualize the results and evaluated by receiver operating characteristic curves and calibration curves.ResultsA total of 437 nurses were recruited. 54% of the nurses had insomnia according to the Insomnia Severity Index (ISI) score. Eleven variables, including family structure, years of work experience, relaxation time, respiratory system sequelae, nervous system sequelae, others sequelae, attitudes toward COVID-19, sleep duration before infection, previous sleep problems, stress, and job burnout, were independently associated with insomnia. The R-squared value was 0.464, and the area under the curve was 0.866. The derived nomogram showed that neurological sequelae, stress, job burnout, sleep duration before infection, and previous sleep problems contributed the most to insomnia. The calibration curves showed significant agreement between the nomogram models and actual observations.ConclusionThis study focused on insomnia among nurses with long COVID-19 and identified eleven risk factors related to nurses’ insomnia. A nomogram model was established to illustrate and visualize these factors, which will be instrumental in future research for identifying nurses with insomnia amid pandemic normalization and may increase awareness of the health status of healthcare workers with long COVID-19.

Structural basis for VLDLR recognition by eastern equine encephalitis virus

Eastern equine encephalitis virus (EEEV) is the most virulent alphavirus that infects humans, and many survivors develop neurological sequelae, including paralysis and intellectual disability. Alphavirus spike proteins comprise trimers of heterodimers of glycoproteins E2 and E1 that mediate binding to cellular receptors and fusion of virus and host cell membranes during entry. We recently identified very-low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as cellular receptors for EEEV and a distantly related alphavirus, Semliki Forest virus (SFV). Here, we use single-particle cryo-electron microscopy (cryo-EM) to determine structures of the EEEV and SFV spike glycoproteins bound to the VLDLR ligand-binding domain and found that EEEV and SFV interact with the same cellular receptor through divergent binding modes. Our studies suggest that the ability of LDLR-related proteins to interact with viral spike proteins through very small footprints with flexible binding modes results in a low evolutionary barrier to the acquisition of LDLR-related proteins as cellular receptors for diverse sets of viruses.

Nirmatrelvir/ritonavir treatment and risk for postacute sequelae of COVID-19 in older Singaporeans

ObjectivesSignificant heterogeneity has been reported in cohort studies evaluating the impact of early oral antiviral treatment on preventing postacute sequelae after COVID-19. We evaluated the impact of early nirmatrelvir/ritonavir on risk of postacute cardiovascular, neurological, respiratory, and autoimmune diagnoses, as well as postacute symptoms amongst older Singaporeans. MethodsNational COVID-19 registries and healthcare claims databases were used to construct a retrospective population-based cohort enrolling all Singaporeans aged ≥60 years diagnosed with SARS-CoV-2 infection in primary care during Omicron transmission (18 March 2022–4 August 2023). The cohort was divided into nirmatrelvir/ritonavir-treated and untreated groups. Between-group differences in baseline characteristics were adjusted using overlap weighting. Risks of postacute cardiovascular, neurological, respiratory, and autoimmune diagnoses and postacute symptoms (31–180 days) after SARS-CoV-2 infection were contrasted in treated/untreated groups using competing risks regressions (adjusted for demographics/vaccination status/comorbidities). ResultsA total of 188 532 older Singaporeans were included; 5.8% (10 905/188 532) received nirmatrelvir/ritonavir. No significantly decreased risk of postacute sequelae (any sequelae: adjusted hazards ratio [aHR], 1.06; 0.94–1.19; cardiovascular sequelae: aHR, 1.01; 0.83–1.24; neurological sequelae: aHR, 1.09; 0.95–1.27; respiratory sequelae: aHR, 1.14; 0.84–1.55; autoimmune sequelae: aHR, 0.76; 0.53–1.09; or any postacute symptom: aHR, 0.97; 0.80–1.18) was observed up to 180 days post-infection in nirmatrelvir/ritonavir-treated individuals vs. untreated cases. Across all vaccination and age subgroups, no significantly decreased risk of any postacute diagnosis/symptom or any cardiovascular, neurological, respiratory, and autoimmune complications up to 180 days post-infection was observed. DiscussionEarly outpatient receipt of nirmatrelvir/ritonavir did not significantly reduce risk of postacute cardiovascular, neurological, respiratory, and autoimmune sequelae or the risk of postacute symptoms in a boosted cohort of older Singaporeans.

Herpes simplex virus in infancy: Evaluation of national surveillance case capture.

As herpes simplex virus (HSV) in infancy is not a mandatory notifiable condition in Australia, completeness of ascertainment by the Australian Paediatric Surveillance Unit (APSU) has been difficult to evaluate to date. We evaluated case capture in Queensland (QLD) and Western Australia (WA) using statewide laboratory and clinical data and complementary surveillance data collected via the APSU. HSV polymerase chain reaction positive results in infants (0-3 months) from 2007 to 2017 were obtained from statewide public pathology providers in QLD and WA. Clinical data were extracted from patient records and compared to APSU reported cases. A total of 94 cases of HSV disease in infancy (70 QLD; 24 WA) were identified from laboratory data sets, compared to 36 cases (26 QLD; 10 WA) reported to the APSU. In total there was 102 unique cases identified; 28 cases were common to both data sets (seven skin eye mouth (SEM) disease, 13 central nervous system (CNS)disease and eight disseminated disease). Active surveillance captured 35% (36/102) of cases overall including 74% (14/19) of CNS, 71% (10/14) of disseminated and 17% (12/69) of SEM disease cases, respectively. Surveillance reported cases had a higher case-fatality rate compared to those not reported (14% vs. 3%, P = 0.038). Neurological sequelae at discharge were comparable between the groups. Active surveillance captures one third of hospitalised HSV cases in QLD and WA, including the majority with severe disease. However, morbidity and mortality remain high. Future studies on HSV will rely on observational studies. Enhanced case ascertainment through combined laboratory and surveillance data is essential for better understanding and improving outcomes.