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Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond adaptive immune cells and provides an entry point toward developing biomarkers and targeted treatments of patients with COVID-19.
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COVID-19/metabolismo , Células Eritroides/patología , Megacariocitos/fisiología , Células Plasmáticas/fisiología , SARS-CoV-2/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Circulación Sanguínea , COVID-19/inmunología , Células Cultivadas , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Proteómica , Análisis de Secuencia de ARN , Índice de Severidad de la Enfermedad , Análisis de la Célula IndividualRESUMEN
INTRODUCTION: In light of the SARS-CoV-2 pandemic, protecting vulnerable groups has become a high priority. Persons at risk of severe disease, for example, those receiving immunosuppressive therapies for chronic inflammatory cdiseases (CIDs), are prioritised for vaccination. However, data concerning generation of protective antibody titres in immunosuppressed patients are scarce. Additionally, mRNA vaccines represent a new vaccine technology leading to increased insecurity especially in patients with CID. OBJECTIVE: Here we present for the first time, data on the efficacy and safety of anti-SARS-CoV-2 mRNA vaccines in a cohort of immunosuppressed patients as compared with healthy controls. METHODS: 42 healthy controls and 26 patients with CID were included in this study (mean age 37.5 vs 50.5 years). Immunisations were performed according to national guidelines with mRNA vaccines. Antibody titres were assessed by ELISA before initial vaccination and 7 days after secondary vaccination. Disease activity and side effects were assessed prior to and 7 days after both vaccinations. RESULTS: Anti-SARS-CoV-2 antibodies as well as neutralising activity could be detected in all study participants. IgG titres were significantly lower in patients as compared with controls (2053 binding antibody units (BAU)/mL ±1218 vs 2685±1102). Side effects were comparable in both groups. No severe adverse effects were observed, and no patients experienced a disease flare. CONCLUSION: We show that SARS-CoV-2 mRNA vaccines lead to development of antibodies in immunosuppressed patients without considerable side effects or induction of disease flares. Despite the small size of this cohort, we were able to demonstrate the efficiency and safety of mRNA vaccines in our cohort.
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Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , Huésped Inmunocomprometido/inmunología , Inmunogenicidad Vacunal/inmunología , Inflamación/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Estudios de Cohortes , Femenino , Humanos , Inmunosupresores/uso terapéutico , Inflamación/inmunología , Masculino , Persona de Mediana Edad , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/inmunología , SARS-CoV-2 , Vacunas Sintéticas/inmunología , Vacunas de ARNmRESUMEN
PURPOSE: To detect possible neuronal damage due to recurrent isolated seizures in patients with epilepsy in a clinical routine setting. METHODS: We measured the serum concentrations of neurofilament light chain (sNfL) in 46 outpatients with an at least monthly occurrence (self-reported) of generalized tonic-clonic seizures in the six months prior to the study and in 49 patients who had been seizure free (self-reported) for at least one year. We assigned the patients with seizure activity into groups with moderate and high seizure frequency. We measured sNfL with a highly sensitive single molecule array (Simoa). RESULTS: The majority (94 %) of all patients with epilepsy had sNfL values within the age adjusted reference ranges of our laboratory. Three patients with and three patients without seizure activity (each 3 %) showed elevated sNfL concentrations. Age adjusted sNfL concentrations did not differ significantly between patients with and without seizure activity in the total sample or in the female subgroup. In contrast, NfL concentrations were significantly higher in male patients with seizure activity and highest in the subgroup of those with high seizure activity, but were only above the reference range in two patients. sNfL concentrations did not differ between focal and generalized epilepsies and between genetic and structural etiologies. CONCLUSIONS: The sNfL concentrations in patients with epilepsy and healthy patients did not differ significantly. The finding of higher sNfL concentrations in males with self-reported seizure activity should be viewed with utmost caution because the difference was small and only two male patients showed sNfL concentrations above the reference range.
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In addition to its role in bone metabolism, vitamin D3 exerts immunomodulatory effects and has been proposed to contribute to seasonal variation of immune cells. This might be linked to higher vitamin D3 levels in summer than in winter due to differential sun exposure. γδ T cells comprise a numerically small subset of T cells in the blood, which contribute to anti-infective and antitumor immunity. We studied the seasonal fluctuation of γδ T cells, the possible influence of vitamin D3, and the effect of the active metabolite 1α,25(OH)2D3 on the in vitro activation of human γδ T cells. In a retrospective analysis with 2625 samples of random blood donors, we observed higher proportions of γδ T cells in winter when compared with summer. In a prospective study over one year with a small cohort of healthy adults who did or did not take oral vitamin D3 supplementation, higher proportions of γδ T cells were present in donors without oral vitamin D3 uptake, particularly in spring. However, γδ T cell frequency in blood did not directly correlate with serum levels of 25(OH)D3. The active metabolite 1α,25(OH)2D3 inhibited the in vitro activation of γδ T cells at the level of proliferation, cytotoxicity, and interferon-γ production. Our study reveals novel insights into the seasonal fluctuation of γδ T cells and the immunomodulatory effects of vitamin D3.
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Calcitriol , Colecalciferol , Adulto , Calcitriol/farmacología , Colecalciferol/farmacología , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Estaciones del AñoRESUMEN
BACKGROUND: There are only few reports on ocular symptoms and manifestations in association with coronavirus disease 2019 (COVID-19). OBJECTIVE: The aim of this study is to describe ocular manifestations in the anterior and posterior segments of the eye and to analyze viral prevalence in tears of patients with COVID-19. METHODS: Hospitalized COVID-19 patients treated from 16 April 2020 to 7 January 2021â¯at this hospital were screened for ocular manifestations in the anterior and posterior segments. Conjunctival swabs were analyzed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. RESULTS: A total of 37 patients were enrolled in this study. In the anterior segment we found chemosis of the conjunctiva (5), hyposphagma (2) and conjunctivitis (1). In 11 patients vascular alterations and potentially disease-specific manifestations of the fundus were found in one or both eyes: retinal hemorrhages (5), cotton wool spots (5) and tortuosity (5). One patient demonstrated branch artery occlusion, one had branch retinal vein occlusion and two patients had positive conjunctival swab results in one or both eyes. CONCLUSION: Our findings of the anterior segment are commonly known, although not specific for COVID-19. Various vascular fundus abnormalities were found in the study; however, it is unclear whether these were correlated to systemic comorbidities or whether they were caused or exacerbated by COVID-19. This study suggests that the risk of viral transmission via tears is low.
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COVID-19 , COVID-19/epidemiología , Conjuntiva , Humanos , ARN Viral , SARS-CoV-2 , LágrimasRESUMEN
In patients with severe #COVID19, increased levels of autoantibodies against PAR1 were found. These might serve as allosteric agonists of PAR1 on endothelial cells and platelets, and thus might contribute to the pathogenesis of microthrombosis in COVID-19. https://bit.ly/3pqM9Vv.