RESUMO
BACKGROUND: Immunity to SARS-CoV-2 vaccination and infection differs considerably among individuals. We investigate the critical pathways that influence vaccine-induced cross-variant serological immunity among individuals at high-risk of COVID-19 complications. METHODS: Neutralizing antibodies to the wild-type SARS-CoV-2 virus and its variants (Beta, Gamma, Delta and Omicron) were analyzed in patients with autoimmune diseases, chronic comorbidities (multimorbidity), and healthy controls. Antibody levels were assessed at baseline and at different intervals up to 12 months following primary and booster vaccination with either BNT162b2 or mRNA-1273. Immunity induced by vaccination with and without infection (hybrid immunity) was compared with that of unvaccinated individuals with recent SARS-CoV-2 infection. Plasma cytokines were analyzed to investigate variations in antibody production following vaccination. RESULTS: Patients with autoimmune diseases (n = 137) produced lesser antibodies to the wild-type SARS-CoV-2 virus and its variants compared with those in the multimorbidity (n = 153) and healthy groups (n = 229); antibody levels were significantly lower in patients with neuromyelitis optica and those on prednisolone, mycophenolate or rituximab treatment. Multivariate logistic regression analysis identified neuromyelitis optica (odds ratio 8.20, 95% CI 1.68-39.9) and mycophenolate (13.69, 3.78-49.5) as significant predictors of a poorer antibody response to vaccination (i.e, neutralizing antibody <40%). Infected participants exhibited antibody levels that were 28.7% higher (95% CI 24.7-32.7) compared to non-infected participants six months after receiving a booster vaccination. Individuals infected during the Delta outbreak generated cross-protective neutralizing antibodies against the Omicron variant in quantities comparable to those observed after infection with the Omicron variant itself. In contrast, unvaccinated individuals recently infected with the wild-type (n = 2390) consistently displayed lower levels of neutralizing antibodies against both the wild-type virus and other variants. Pathway analyses suggested an inverse relationship between baseline T cell subsets and antibody production following vaccination. CONCLUSION: Hybrid immunity confers a robust protection against COVID-19 among immunocompromised individuals.
RESUMO
The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR < 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.
RESUMO
Dysferlin is a sarcolemmal protein present in muscle cells. It is responsible for muscle membrane repair. Dysferlin gene (DYSF) mutation, resulting in deficiency in this protein, is termed dysferlinopathy. Clinically, it manifests as early adulthood onset of muscle weakness with markedly elevated creatine kinase levels. The main phenotypes are limb-girdle muscular dystrophy type 2B (LGMD2B), affecting proximal muscles, and Miyoshi myopathy (MM), affecting distal muscles. Dysferlin is also present in cardiomyocytes, and case reports have emerged of cardiac abnormalities in dysferlinopathy. While routine methods of cardiac screening, namely, electrocardiography or echocardiography, are convenient and noninvasive, they often exhibit insufficient diagnostic sensitivity for detecting subclinical cardiac remodeling during early stages of cardiomyopathy. Cardiac magnetic resonance imaging though can provide accurate assessment of cardiac chamber sizes and function. With gadolinium administration, it can also detect areas of myocardial scarring and fibrosis. Early diagnosis of neuromuscular disease-related cardiomyopathy is of clinical significance, as appropriate treatment can retard myocardial fibrosis, delaying cardiomyopathy progression. We present a case of a patient with MM incidentally diagnosed with concomitant cardiomyopathy.
Assuntos
Técnicas de Imagem Cardíaca , Cardiomiopatias/etiologia , Miopatias Distais/complicações , Gadolínio , Imageamento por Ressonância Magnética , Atrofia Muscular/complicações , Adulto , Cardiomiopatias/diagnóstico por imagem , Feminino , HumanosRESUMO
PURPOSE: To describe the spectrum of COVID-19 neurology in Singapore. METHOD: We prospectively studied all microbiologically-confirmed COVID-19 patients in Singapore, who were referred for any neurological complaint within three months of COVID-19 onset. Neurological diagnoses and relationship to COVID-19 was made by consensus guided by contemporaneous literature, refined using recent case definitions. RESULTS: 47,572 patients (median age 34 years, 98% males) were diagnosed with COVID-19 in Singapore between 19 March to 19 July 2020. We identified 90 patients (median age 38, 98.9% males) with neurological disorders; 39 with varying certainty of relationship to COVID-19 categorised as: i) Central nervous system syndromes-4 acute disseminated encephalomyelitis (ADEM) and encephalitis, ii) Cerebrovascular disorders-19 acute ischaemic stroke and transient ischaemic attack (AIS/TIA), 4 cerebral venous thrombosis (CVT), 2 intracerebral haemorrhage, iii) Peripheral nervous system-7 mono/polyneuropathies, and a novel group, iv) Autonomic nervous system-4 limited dysautonomic syndromes. Fifty-one other patients had pre/co-existent neurological conditions unrelated to COVID-19. Encephalitis/ADEM is delayed, occurring in critical COVID-19, while CVT and dysautonomia occurred relatively early, and largely in mild infections. AIS/TIA was variable in onset, occurring in patients with differing COVID-19 severity; remarkably 63.2% were asymptomatic. CVT was more frequent than expected and occurred in mild/asymptomatic patients. There were no neurological complications in all 81 paediatric COVID-19 cases. CONCLUSION: COVID-19 neurology has a wide spectrum of dysimmune-thrombotic disorders. We encountered relatively few neurological complications, probably because our outbreak involved largely young men with mild/asymptomatic COVID-19. It is also widely perceived that the pandemic did not unduly affect the Singapore healthcare system.
Assuntos
COVID-19/epidemiologia , Doenças do Sistema Nervoso/epidemiologia , Adulto , Comorbidade , Feminino , Humanos , Masculino , Pandemias , Estudos Prospectivos , SARS-CoV-2 , Singapura/epidemiologia , Adulto JovemRESUMO
PURPOSE: The significance of periodic EEG patterns in patients with impaired consciousness is controversial. We aimed to determine if treating these patterns influences clinical outcome. METHOD: We studied all patients who had periodic discharges on their EEG recordings from January 2007 to December 2009. Patients with clinical seizures within the preceding 24h, or with unequivocal electrographical seizure activity were excluded. Logistic regression was performed to analyze for factors associated with (a) mortality (b) functional status (c) resolution of EEG pattern. RESULTS: Of the 4246 patients who had EEG, 111 (2.6%) had periodic EEG patterns. 64 met inclusion criteria. In adjusted analysis, higher mortality was associated with acute symptomatic etiology (OR 17.74, 95% CI 1.61-196.07, p=0.019), and presence of clinical seizures (OR 4.73, 95% CI 1.10-20.34, p=0.037). For each unit decrement of GCS, the odds of inpatient mortality and a poorer functional state on discharge increased by 23% (95% CI 7-37%, p=0.009) and 33% (95% CI 9-51%, p=0.011) respectively. Administration of abortive therapy was an independent risk factor for poorer functional status on discharge (adjusted OR 41.39, 95% CI 2.88-594.42, p=0.006), while patients with history of pre-existing cerebral disease appeared more likely to return to baseline functional status on discharge (unadjusted OR 5.00, 95% CI 1.40-17.86, p=0.013). CONCLUSION: Treatment of periodic EEG patterns does not independently improve clinical outcome of patients with impaired conscious levels. Occurrence of seizures remote to the time of EEG and lower GCS scores independently predict poor prognoses.
Assuntos
Encéfalo/fisiopatologia , Transtornos da Consciência/fisiopatologia , Transtornos da Consciência/terapia , Idoso , Transtornos da Consciência/mortalidade , Eletroencefalografia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Convulsões/fisiopatologia , Resultado do TratamentoRESUMO
INTRODUCTION: Organisms of the Streptococcus milleri group consists of Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus. Though they are commonly associated with abscesses, bacteremia with subsequent septic shock and mortality is infrequent. CASE PRESENTATION: We report a case of a 27-year-old Chinese man who presented with Streptococcus constellatus bacteremia following an incomplete tooth extraction resulting in septic shock. CONCLUSION: Bacteremia from the Streptococcus milleri group is infrequent but must trigger the search for an underlying abscess. Knowledge of each member's predilection for different clinical presentations can aid in determining the location of the underlying source of infection.