Convalescent Phase Research Articles

Clinical characteristics, management, and prevention of coronavirus disease 2019

Abstract Coronavirus disease 2019 (COVID-19) is the third severe acute respiratory disease of the 21st century and the most aggressive global pandemic to date. The whole population has been susceptible to the disease, particularly the emerging variants of the virus. The core pathophysiological mechanism is viral sepsis that can lead to the respiratory tract disorders and even systemic disorders such as cytokine release syndrome, thrombosis, abnormal angiogenesis, and multiple organ dysfunction. Despite only few licensed treatments to date, rapid advances have been made in exploring the effectiveness and safety of pharmacological interventions and vaccines. However, three pillars of preventative and control measures - proactive contact tracing, wearing facial masks, and social distancing - are essential to combat the ongoing pandemic. As the number of patients recovering from COVID-19 rapidly increases, the world has entered the era of caring for patients during the convalescence phase. This phase still represents a largely unmet medical need globally.

Clinical Profile of SARS-CoV-2 Infection: Mechanisms of the Cellular Immune Response and Immunogenetic Markers in Patients from Brazil.

The aim of this study is to evaluate some mechanisms of the immune response of people infected with SARS-CoV-2 in both acute infection and early and late convalescence phases. This is a cohort study of 70 cases of COVID-19, confirmed by RT-PCR, followed up to 60 days. Plasma Samples and clinical data were. Viral load, blood count, indicators inflammation were the parameters evaluated. Cellular immune response was evaluated by flow cytometry and Luminex immunoassays. In the severe group, hypertension was the only reported comorbidity. Non severe patients have activated memory naive CD4+ T cells. Critically ill patients have central memory CD4+ T cell activation. Severe COVID-19 patients have both central memory and activated effector CD8+ T cells. Non-severe COVID-19 cases showed an increase in IL1β, IL-6, IL-10 and TNF and severely ill patients had higher levels of the cytokines IL-6, IL-10 and CXCL8. The present work showed that different cellular responses are observed according to the COVID-19 severity in patients from Brazil an epicenter the pandemic in South America. Also, we notice that some cytokines can be used as predictive markers for the disease outcome, possibility implementation of strategies effective by health managers.

Unique Immune Blood Markers Between Severe Dengue and Sepsis in Children.

Pediatric dengue and sepsis share clinical and pathophysiologic aspects. Multiple inflammatory and regulatory cytokines, decoy receptors and vascular permeability factors have been implicated in the pathogenesis of both diseases. The differential pattern and dynamic of these soluble factors, and the relationship with clinical severity between pediatric dengue and sepsis could offer new diagnosis and therapeutic strategies. We evaluated the concentration levels of 11 soluble factors with proinflammatory, regulatory and vascular permeability involvement, in plasma from children with dengue or sepsis, both clinically ranging from mild to severe, in the early, late and convalescence phases of the disease. During early acute infection, children with sepsis exhibited specific higher concentration levels of IL-6, vascular endothelial growth factor (VEGF), and its soluble decoy receptor II (sVEGFR2) and lower concentration levels of IL-10 and the soluble tumor necrosis factor receptor 2 (sTNFR2), in comparison with children with severe dengue. In addition, the circulating amounts of soluble ST2, and VEGF/sVEGFR2 were widely associated with clinical and laboratory indicators of dengue severity, whereas secondary dengue virus infections were characterized by an enhanced cytokine response, relative to primary infections. In severe forms of dengue, or sepsis, the kinetics and the cytokines response during the late and convalescence phases of the disease also differentiate. Dengue virus infection and septic processes in children are characterized by cytokine responses of a specific magnitude, pattern and kinetics, which are implicated in the pathophysiology and clinical outcome of these diseases.

Population pharmacokinetic/pharmacodynamic target attainment of ceftriaxone 2 g once daily in non-critically ill hospitalized adult patients during the acute phase of infection.

Pharmacokinetic/pharmacodynamic target attainment of ceftriaxone is compromised in intensive care unit (ICU) patients and non-ICU hospitalized patients in Beira, Mozambique. Whether this also accounts for non-ICU patients in a high-income setting is unknown. We therefore assessed the probability of target attainment (PTA) of the currently recommended dosing regimen of 2 g every 24 h (q24h) in this patient group. We performed a multicentre population pharmacokinetic study in hospitalized non-ICU adult patients empirically treated with intravenous ceftriaxone. During both the acute phase of infection (i.e. first 24 h of treatment) and convalescence, a maximum of 4 random blood samples were obtained per patient for ceftriaxone total and unbound concentration measurements. PTA was calculated using NONMEM and was defined as the percentage of patients of which the unbound ceftriaxone concentration exceeded the minimum inhibitory concentration (MIC) for >50% of the first dosing interval of 24 h. Monte Carlo simulations were performed to determine PTA for different estimated glomerular filtration rates (eGFR; CKD-EPI) and MICs. PTA >90% was considered adequate. Forty-one patients provided 252 ceftriaxone total and 253 unbound concentrations. The median eGFR was 65 mL/min/1.73 m2 (5th to 95th percentile 36-122). With the recommended dose of 2 g q24h, PTA >90% was achieved for bacteria with an MIC ≤2 mg/L. Simulations showed that PTA was insufficient for an MIC of 4 mg/L in case the eGFR was 122 mL/min/1.73 m2 (PTA 56.9%) and for an MIC of 8 mg/L regardless of eGFR. The PTA of 2 g q24h ceftriaxone dosing is adequate for common pathogens during the acute phase of infection in non-ICU patients.

The Result of the Treatment of Optic Nerve Edema after COVID-19

The neuro-ophthalmic symptoms and signs associated with COVID-19 infection are varied and span the course of the infection to the convalescent phase. In addition to the anterior segment of the eye, there is a possibility of damage to the posterior segment of the eyeball. The described cases are isolated and there are no results of treatment of patients who have undergone COVID-19.Purpose: To describe the outcome of treatment of bilateral optic nerve edema after COVID-19.Methods. A 59-year-old man with reduced visual functions in the post-surgical period was examined. A standard ophthalmological examination was performed. In addition, spectral optical coherence tomography (OCT) of the macular area of the retina and optic disc (OND) was performed using the RTVue XR Avanti apparatus (Optovue, USA). The patient underwent a laboratory study.Results. Bilateral papilledema was detected in a patient after COVID-19. According to OCT data, a thickening of the nerve fiber layer of the retina of both eyes was revealed, according to OCT angiography, a decrease in the density of the RPC. Conducted a course of conservative and physiotherapy treatment.Conclusion. The COVID-19 epidemic poses several challenges for the ophthalmological community: to determine algorithms for timely diagnosis and treatment, as well as to ensure the prevention of complications from the organ of vision in patients who have undergone COVID-19. It may make sense to screen for coronaviruses in patients with inflammatory diseases of the posterior segment of the eye of unknown etiology. The inclusion of spectral optical coherence tomography with the function of angiography in a comprehensive examination of patients is important for the early detection of microcirculatory and morphometric changes in the optic disc, macular and peripapillary retina. It is advisable to use physiotherapeutic methods of treatment in patients with visual impairment in the post-COVID period, which will reduce the long-term drug load and increase the effectiveness of treatment.

Left atrial subclinical dysfunction in children with Kawasaki disease: a two-dimensional speckle-tracking echocardiography study.

Left atrial (LA) function is a very important prognostic indicator for many cardiovascular diseases. In this study, we aimed to determine whether LA function is impaired in children with Kawasaki disease (KD) and to analyze the relationships between LA deformation and conventional echocardiographic parameters and laboratory markers. A total of 50 KD patients during different disease phases and 50 age- and sex-matched controls were retrospectively analyzed. Patients in the acute phase based on coronary artery dilation (CAD) were subdivided into Group I (with CAD) and Group II (without CAD) and compared. During the acute phase, KD patients had a lower peak LA longitudinal strain (PLALS), a lower LA strain peak during LA contraction (LASct), and a lower LA strain rate peak during LA contraction (LASRct) than the controls. The PLALS, LASct and LASRct began to increase during the subacute phase, and during the convalescent phase, all LA strains in patients had recovered to normal compared with the control subjects. Subgroup analysis revealed that, compared with Group II, Group I had higher C-reactive protein (CRP) and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels; however, there were no significant differences in LA strains. Only the PLALS during the acute phase was negatively correlated with left ventricular mass index, CRP and NT-proBNP. In patients with KD, LA function is impaired during the acute phase, and this impairment is transient. Two-dimensional speckled tracking echocardiography is a useful tool for detecting subclinical LA dysfunction.

Determining Differentially Expressed Genes in Dengue Patients During Disease Progression

Gene expression studies on gene transcription to synthesize functional gene products have been used extensively to understand biological differences between different disease conditions. Thus, this study determines differentially expressed genes in dengue infection during disease progression following the three phases: Febrile, Defervescence and Convalescent. Integrative data analysis of two publicly available longitudinal datasets in Gene Expression Omnibus (GEO) database has been employed to accomplish the prime objective of exploring temporal gene expression patterns. The Friedman test was given more emphasis due to the non-normality distributions of data. Repeated measures analysis of variance (ANOVA) and linear mixed models were also implemented to examine the potential of detecting differentially expressed genes despite non-normality. The Friedman test revealed significant differences in gene expression levels across different phases in dengue disease over time. This led to a notably higher count of genes showing differential expression compared to the other two methods: Repeated measures ANOVA and linear mixed models. The pathway analysis approach consists of significant differentially expressed genes derived from the Friedman test. The results identified upregulated pathways with any significant change in the overall expression of genes within pathways over time for the Febrile and Defervescence phases considering the Convalescent phase as a baseline. Moreover, genes available in pathways were not identified by the two parametric tests for non-normal data implying that the parametric approaches resulted in the least significance for data with non-normal distributions.

Transformation Concept of Artificial Intelligencein the Early Identification of Tuberculosis Recovery Phase: A Systematic Literature Review

Background: Another chronic problem in tuberculosis (TB) eradication programs amid the widespread use of artificial intelligence (AI) in the health world is that early identification of the healing phase has not been found using similar technology. The purpose is to find if the transformation concept of AI will be able to help identify symptoms of early recovery of TB. Methods: This research used a document review with a descriptive design. Data was processed by PRISMA analysis. The keywords were Artificial Intelligence, convalescence phase, and tuberculosis. The data were filtered from Google Engine included from Google Scholar, ResearchGate, PubMed, and Semantic Scholar screened in the last 5 years (2018-2023), in English or Indonesian. The stages of document screening were adjusted to the PRISMA diagram, and were analyzed descriptively. Results: The study shows that the majority of AI studies discussed diagnosis (n=9 or 69.2%), only 3 documents (23.1%) discussed on TB treatment, and 1 document (7.7%) on monitoring. In conclusion, early identification of the recovery phase of TB patients is supported by previous researchers and can be done in the form of an application. Conclusions: Artificial intelligence in the TB eradication program has value especially if conducted integrated with other health programs.

Changes of gut microbiota in patients at different phases of stroke.

Gut dysbiosis appears rapidly after acute stroke and may affect the prognosis, whereas changes in gut microbiota with gradual recovery from stroke are unknown and rarely studied. The purpose of this study is to explore the characteristics of gut microbiota changes over time after stroke. Stroke patients and healthy subjects were selected to compare the clinical data and gut microbiota of the patient group in two phases with that of healthy subjects and 16S rRNA gene sequencing was used to search the differences of gut microbiota in subjects. Compared with the healthy subjects, the subacute patients mainly decreased the abundance of some gut microbial communities, while the decreased communities reduced and more communities increased the abundance in the convalescent patients. The abundance of Lactobacillaceae increased in both phases in patient group, while Butyricimona, Peptostreptococaceae and Romboutsia decreased in both phases. Correlation analysis found that the MMSE scores of patients in the two phases had the greatest correlation with the gut microbiota. Gut dysbiosis still existed in patients in the subacute phase and convalescent phase, and gradually improved with the recovery of stroke. Gut microbiota may affect the prognosis of stroke by affecting BMI and/or related indicators, and there is a strong correlation between gut microbiota and cognitive function after stroke.

Emerging role of computed tomography coronary angiography in evaluation of children with Kawasaki disease.

Coronary artery abnormalities are the most important complications in children with Kawasaki disease (KD). Two-dimensional transthoracic echocardiography currently is the standard of care for initial evaluation and follow-up of children with KD. However, it has inherent limitations with regard to evaluation of mid and distal coronary arteries and, left circumflex artery and the poor acoustic window in older children often makes evaluation difficult in this age group. Catheter angiography (CA) is invasive, has high radiation exposure and fails to demonstrate abnormalities beyond lumen. The limitations of echocardiography and CA necessitate the use of an imaging modality that overcomes these problems. In recent years advances in computed tomography technology have enabled explicit evaluation of coronary arteries along their entire course including major branches with optimal and acceptable radiation exposure in children. Computed tomography coronary angiography (CTCA) can be performed during acute as well as convalescent phases of KD. It is likely that CTCA may soon be considered the reference standard imaging modality for evaluation of coronary arteries in children with KD.

Bilateral acute angle closure attack precipitated with dengue fever

Dengue is known to cause varied ocular problems from mild-to-severe sight threatening. We present the case of a 63-year-old female patient with bilateral shallow anterior chamber and acute angle closure attack precipitated during the convalescent phase of dengue infection. She arrived at the emergency department at midnight with a history of vomiting, headache, weakness, and pain in the left eye (LE). Her diagnosis of dengue fever was supported by specific serological testing. On ocular examination, the anterior chamber of both eyes was noticeably shallow and her LE felt stony hard on digital palpation. Intravenous mannitol 300 mL over 45 min were given stat followed by topical medications. In the morning, intraocular pressure measured was 10 mmHg (right eye [RE]) and 26 mmHg (LE). After thorough examination, she was diagnosed with occludable angle in RE and angle closure in LE after gonioscopy. Neodymium-doped Yttrium Aluminum Garnet laser peripheral iridotomy was done in both eyes. She was relieved of symptoms. The varied spectrum of possible ocular symptoms should prompt the ophthalmologist to suspect the potential involvement of eye in dengue fever. Detailed history taking is of utmost importance in early diagnosis of some rare presentation of dengue-related ophthalmic involvement. Increased awareness of dengue-related ophthalmic complications among clinicians involved in the care of patients with dengue would facilitate prompt ophthalmologic assessment and emergency medical care.

Mailuoning oral liquid attenuates convalescent cerebral ischemia by inhibiting AMPK/mTOR-associated apoptosis and promoting CREB/BDNF-mediated neuroprotection

Ethnopharmacological relevanceIschemic stroke is divided into acute, subacute and convalescent phases according to the time of onset. Clinically, Mailuoning oral liquid (MLN O) is a traditional Chinese patent medicine for treating ischemic stroke. Previous studies have shown that MLN O could prevent acute cerebral ischemia-reperfusion. However, its underlying mechanism remains unclear. Aim of the studyTo investigate the relationship between neuroprotection and apoptosis for clarifying MLN O mechanism in the recovery phase of ischemic stroke. Materials and methodsWe imitated stroke using middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro models. The infarct volume, neurological deficit scores, HE staining, Nissl staining, TUNEL staining, immunohistochemistry, and Western blot were correspondingly performed to find pathological changes and detect neuronal apoptosis in rat cerebral cortex. The contents of LDH, Cyt-c, c-AMP and BDNF in rat plasma and cerebral cortex were detected by ELISA. Cell viability was measured by CCK8 assay. Cell morphology, Hoechst 33342 staining and Annexin-V-Alexa Fluor 647/PI staining were performed to assess neuronal apoptosis. The expression levels of proteins were evaluated by western blotting. ResultsMLN O obviously reduced brain infarct volume and neurological deficit scores in MCAO rats. MLN O inhibited inflammatory cell infiltration and neuronal apoptosis, but promoted gliosis, neuronal survival, and neuroprotection in the cortical region of MCAO rats. Additionally, MLN O decreased the amount of LDH and cytochrome c, while increasing the expression of c-AMP in the plasma and ischemic cerebral cortex of MCAO rats, and promoting the expression of BDNF in the cortical tissue of MCAO rats. Besides, MLN O improved cell viability, restored cell morphology, while attenuating cell damage, inhibiting neuronal apoptosis following OGD/R in PC-12 cells. Moreover, MLN O inhibited apoptosis by suppressing the expression of pro-apoptotic-associated proteins, including Bax, cytochrome c, Cleaved caspase 3 and HIF-1α, whereas accelerating the expression of Bcl-2 in vivo and in vitro. Furthermore, MLN O inhibited the activity of AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR), but activated the signaling pathway of cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) in MCAO rats and OGD/R-stimulated PC-12 cells. ConclusionsThese results demonstrated that MLN O inhibited AMPK/mTOR to affect apoptosis associated with mitochondria, leading to improve CREB/BDNF-mediated neuroprotection in the recovery period of ischemic stroke in vivo and in vitro.

Comparison of quantitative FDG-PET and MRI in anti-LGI1 autoimmune encephalitis

ObjectivesAnti-leucine glioma-inactivated protein 1 (anti-LGI1) autoimmune encephalitis (AE) presents as subacute memory loss, behavioral changes, and seizures. Diagnosis and treatment delays can result in long term sequelae, including cognitive impairment. 18F-FDG PET/CT may be more sensitive than MRI in patients with AE. Our objective was to determine if anti-LGI1 is associated with a distinct pattern of FDG uptake and whether this pattern persists following treatment.MethodsNineteen18F-FDG PET/CT brain scans (13 pre-treatment, 6 convalescent phase) for 13 patients with anti-LGI1 were studied using NeuroQ™ and CortexID™. The sensitivity of the PET images was compared to MRI. The Z scores of 47 brain regions between the pre-treatment and next available follow-up images during convalescence were compared.ResultsAll 18F-FDG PET/CT scans demonstrated abnormal FDG uptake, while only 6 (42.9%) pre-treatment brain MRIs were abnormal. The pre-treatment scans demonstrated hypermetabolism in the bilateral medial temporal cortices, basal ganglia, brain stem, and cerebellum and hypometabolism in bilateral medial and mid frontal, cingulate, and parietotemporal cortices. Overall, the brain uptake during convalescence showed improvement of the Z scores towards 0 or normalization of previous hypometabolic activity in medial frontal cortex, inferior frontal cortex, Broca’s region, parietotemporal cortex, and posterior cingulate cortex and previous hypermetabolic activity in medial temporal cortices, caudate, midbrain, pons and cerebellum.ConclusionsBrain FDG uptake was more commonly abnormal than MRI in the pre-treatment phase of anti-LGI1, and patterns of dysmetabolism differed in the pre-treatment and convalescent phases. These findings may expedite the diagnosis, treatment, and monitoring of anti-LGI1 patients.

Dynamics of neutralizing antibodies against severe fever with thrombocytopenia syndrome virus

ObjectivesSevere fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne bunyavirus with a high pathogenicity. Little is known about the longitudinal dynamics of the SFTSV-specific neutralizing antibody (NAb) and the related factors in patients with SFTS. MethodsA prospective cohort study of patients with laboratory-confirmed SFTS were conducted. Antiglomerulonephritis-immunoglobulin G (anti-Gn-IgG) and NAb titers were examined in serially collected serum samples, and their dynamic features were analyzed. ResultsNAb was initially detected at 15 days after symptom onset in surviving patients with SFTS, with positive rates of 37.21% (16/43), whereas neither anti-Gn-IgG antibody nor NAb was detected in patients with fatal SFTS during their hospitalization. The NAb levels reached the peak at 2 months after symptom onset, and then gradually declined, with a rapid downward trend from 6 months to 4 years and a relatively slow downward trend from 5 to 10 years. There was a positive correlation between NAb and anti-Gn-IgG titers in surviving patients with SFTS (r = 0.699, P <0.001). Patients with a mild illness or low viral load experienced early NAb seroconversion. Six different dynamic patterns of NAb were noted in surviving patients. ConclusionThese data provide useful information regarding the dynamic changes in NAb in patients with SFTS during the acute and convalescent phases and the follow-up period.

Pathophysiological Aspects of COVID-19-Associated Vasculopathic Diseases.

Since the beginning of coronavirus disease 2019 (COVID-19) pandemic, numerous data reported potential effects on the cardiovascular system due to infection by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which may lead to COVID-19-associated vasculopathies during the acute phase and measurable vascular changes in the convalescent phase. Infection by SARS-CoV-2 seems to have specific direct and indirect effects on the endothelium, immune and coagulation systems thus promoting endothelial dysfunction, immunothrombosis, and formation of neutrophil extracellular traps although the exact mechanisms still need to be elucidated. This review represents a recent update of pathophysiological pathways of the respective three major mechanisms contributing to COVID-19 vasculopathies and vascular changes and includes clinical implications and significance of outcome data.

First Sampled High-Sensitive Cardiac Troponin T is Associated With One-Year Mortality in Sepsis Patients and 30- to 365-Day Mortality in Sepsis Survivors

BackgroundPrevious studies using cardiac troponin levels to investigate the relationship between myocardial injury and mortality in sepsis patients have been conflicting. Our aim was to investigate the relationship between plasma high-sensitive cardiac troponin T (hs-cTnT) level and 30-day and 1-year mortality in sepsis patients and 30- to 365-day mortality in sepsis survivors. MethodsSepsis patients requiring vasopressor support and admitted to our institution between 2012 and 2021 (n = 586) were included in this retrospective cohort study. Elevated hs-cTnT values (≥15 ng/L) were divided into quartiles (Q): Q1 15-35 ng/L; Q2 36-61 ng/L; Q3 62-125 ng/L; Q4 126-8630 ng/L. Stratified Kaplan-Meier curves and multivariable Cox regression were used for survival analyses. ResultsFirst sampled hs-cTnT was elevated in 529 (90%) patients. One-year mortality was 45% (n = 264). Increasing level of hs-cTnT was independently associated with higher adjusted hazard ratios (HR) for 1-year mortality compared with normal levels: Q1 HR 2.9 (95% confidence interval [CI], 1.03-8.1); Q2 HR 3.5 (95% CI, 1.2-9.8); Q3 HR 4.8 (95% CI, 1.7-13.4); Q4 HR 5.7 (95% CI, 2.1-16). In acute phase survivors, first sampled hs-cTnT was an independent predictor of 30- to 365-day mortality (HR 1.3; 95% CI, 1.1-1.6 per loge hs-cTnT). ConclusionsFirst sampled plasma hs-cTnT in critically ill sepsis patients was independently associated with 30-day and 1-year mortality. Importantly, first sampled hs-cTnT was associated with mortality during the convalescence phase (30- to 365-day) and could be a feasible marker to identify acute phase survivors at high risk of death.

Classification of Vogt-Koyanagi-Harada disease using feature selection and classification based on wide-field swept-source optical coherence tomography angiography.

Background: Vogt-Koyanagi-Harada (VKH) disease is a common and easily blinded uveitis entity, with choroid being the main involved site. Classification of VKH disease and its different stages is crucial because they differ in clinical manifestations and therapeutic interventions. Wide-field swept-source optical coherence tomography angiography (WSS-OCTA) provides the advantages of non-invasiveness, large-field-of-view, high resolution, and ease of measuring and calculating choroid, offering the potential feasibility of simplified VKH classification assessment based on WSS-OCTA. Methods: 15 healthy controls (HC), 13 acute-phase and 17 convalescent-phase VKH patients were included, undertaken WSS-OCTA examination with a scanning field of 15 × 9mm2. 20 WSS-OCTA parameters were then extracted from WSS-OCTA images. To classify HC and VKH patients in acute and convalescent phases, two 2-class VKH datasets (HC and VKH) and two 3-class VKH datasets (HC, acute-phase VKH, and convalescent-phase VKH) were established by the WSS-OCTA parameters alone or in combination with best-corrected visual acuity (logMAR BCVA) and intraocular pressure (IOP), respectively. A new feature selection and classification method that combines an equilibrium optimizer and a support vector machine (called SVM-EO) was adopted to select classification-sensitive parameters among the massive datasets and to achieve outstanding classification performance. The interpretability of the VKH classification models was demonstrated based on SHapley Additive exPlanations (SHAP). Results: Based on pure WSS-OCTA parameters, we achieved classification accuracies of 91.61% ± 12.17% and 86.69% ± 8.30% for 2- and 3-class VKH classification tasks. By combining the WSS-OCTA parameters and logMAR BCVA, we achieved better classification performance of 98.82% ± 2.63% and 96.16% ± 5.88%, respectively. Through SHAP analysis, we found that logMAR BCVA and vascular perfusion density (VPD) calculated from the whole field of view region in the choriocapillaris (whole FOV CC-VPD) were the most important features for VKH classification in our models. Conclusion: We achieved excellent VKH classification performance based on a non-invasive WSS-OCTA examination, which provides the possibility for future clinical VKH classification with high sensitivity and specificity.

Queued viral emergence and risk of global exposure: Langya virus

Queued viral emergence and risk of global exposure: Langya virus

Characterization and Investigation of Risk Factors for Late-Relapsing Hepatitis After Yellow Fever.

Late-relapsing hepatitis after yellow fever (LHep-YF) during the convalescent phase of the disease has been described during recent yellow fever (YF) outbreaks in Brazil. LHep-YF is marked by a rebound in liver enzymes and nonspecific clinical manifestations around 46-60 days after YF symptom onset. Here we have characterized the clinical course and risk factors for LHep-YF using data from a representative cohort of patients who survived YF in Brazil, 2017-2018. A total of 221 YF-positive patients were discharged from the infectious disease reference hospital in Minas Gerais and were followed up at 30, 45, and 60 days post-symptom onset. From 46 to 60 days post-symptom onset, 16% of YF patients (n = 36/221) exhibited a rebound of aminotransferases (aspartate aminotransferase or alanine aminotransferase >500 IU/L), alkaline phosphatase, and total bilirubin levels. Other etiologies of liver inflammation such as infectious hepatitis, autoimmune hepatitis, and metabolic liver disease were ruled out. Jaundice, fatigue, headache, and low platelet levels were associated with LHep-YF. Demographic factors, clinical manifestations, laboratory tests, ultrasound findings, and viral load during the acute phase of YF were not associated with the occurrence of LHep-YF. These findings provide new data on the clinical course of Late-relapsing hepatitis during the convalescent phase of YF and highlight the need for extended patient follow-up after acute YF.

Alterations in immunophenotype and metabolic profile of mononuclear cells during follow up in children with multisystem inflammatory syndrome (MIS-C).

Although children seem to be less susceptible to COVID-19, some of them develop a rare but serious hyperinflammatory condition called multisystem inflammatory syndrome in children (MIS-C). While several studies describe the clinical conditions of acute MIS-C, the status of convalescent patients in the months after acute MIS-C is still unclear, especially the question of persistence of changes in the specific subpopulations of immune cells in the convalescent phase of the disease. We therefore analyzed peripheral blood of 14 children with MIS-C at the onset of the disease (acute phase) and 2 to 6 months after disease onset (post-acute convalescent phase) for lymphocyte subsets and antigen-presenting cell (APC) phenotype. The results were compared with six healthy age-matched controls. All major lymphocyte populations (B cells, CD4 + and CD8+ T cells, and NK cells) were decreased in the acute phase and normalized in the convalescent phase. T cell activation was increased in the acute phase, followed by an increased proportion of γ/δ-double-negative T cells (γ/δ DN Ts) in the convalescent phase. B cell differentiation was impaired in the acute phase with a decreased proportion of CD21 expressing, activated/memory, and class-switched memory B cells, which normalized in the convalescent phase. The proportion of plasmacytoid dendritic cells, conventional type 2 dendritic cells, and classical monocytes were decreased, while the proportion of conventional type 1 dendritic cells was increased in the acute phase. Importantly the population of plasmacytoid dendritic cells remained decreased in the convalescent phase, while other APC populations normalized. Immunometabolic analysis of peripheral blood mononuclear cells (PBMCs) in the convalescent MIS-C showed comparable mitochondrial respiration and glycolysis rates to healthy controls. While both immunophenotyping and immunometabolic analyzes showed that immune cells in the convalescent MIS-C phase normalized in many parameters, we found lower percentage of plasmablasts, lower expression of T cell co-receptors (CD3, CD4, and CD8), an increased percentage of γ/δ DN Ts and increased metabolic activity of CD3/CD28-stimulated T cells. Overall, the results suggest that inflammation persists for months after the onset of MIS-C, with significant alterations in some immune system parameters, which may also impair immune defense against viral infections.