Immune modulation as a consequence of SARS-CoV-2 infection.

Erroneous immune responses in COVID-19 could have detrimental effects, which makes investigation of immune network underlying COVID-19 pathogenesis a requisite. This study aimed to investigate COVID-19 related alterations within the frame of innate and adaptive immunity. Thirty-four patients clinically diagnosed with mild, moderate and severe COVID-19 disease were enrolled in this study. Decreased ILC1 and increased ILC2 subsets were detected in mild and moderate patients compared to healthy controls. NK cell subsets and cytotoxic capacity of NK cells were decreased in severe patients. Moreover, CD3+ T cells were reduced in severe patients and a negative correlation was found between CD3+ T cells and D-dimer levels. Likewise, moderate and severe patients showed diminished CD3+CD8+ T cells. Unlike T and NK cells, plasmablast and plasma cells were elevated in patients and IgG and IgA levels were particularly increased in severe patients. Severe patients also showed elevated serum levels of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-8, reduced intracellular IFN-γ and increased intracellular IL-10 levels. Our findings emphasize that SARS-CoV-2 infection significantly alters immune responses and innate and acquired immunity are differentially modulated in line with the clinical severity of the disease. Elevation of IL-10 levels in NK cells and reduction of CD3+ and CD8+ T cells in severe patients might be considered as a protective response against the harmful effect of cytokine storm seen in COVID-19.

The modulatory action of C-Vx substance on the immune system in COVID-19.

The modulatory effect of C-Vx, a novel therapeutic agent, on the immune system of COVID-19 patients was investigated. The functions of T and NK cells of COVID-19 patients with different disease severity were evaluated by flow cytometry in response to C-Vx stimulation. The levels of pro- and anti-inflammatory cytokines were detected by multiplex assay in supernatants after cell culture with C-Vx. Bradykinin, IRF3, and IFN-α levels were also measured by ELISA in the presence or absence of C-Vx stimulation. As a result, increased CD107a expression was observed on NK cells in response to C-Vx addition. The proliferation of T cell subsets was increased by C-Vx, decreasing by disease severity. IL-4 and IL-10 levels were elevated while IFN-γ and IL-17 levels were reduced in T cells following C-Vx stimulation. However, the levels of pro-inflammatory IL-1ß, IL-6, IL-8, IFN-γ and GM-CSF were significantly increased upon C-Vx stimulation. IFN-α levels tended to increase after incubation with C-Vx. These findings support an immunomodulatory action of C-Vx on the immune system of patients with a mild and moderate phase of COVID-19.

Do the neurologists recognize autoimmune epilepsy well enough? What is the effect of the pandemic on this matter?

INTRODUCTION: The concept of "autoimmune epilepsy" (AE) has been emphasized more frequently through the recent increase in recognition of various autoantibodies specific to neuronal proteins. AIMS: To evaluate the attitudes of neurologists in regard to AE, to review the differential diagnosis, treatment options, and to reveal the effect of COVID-19 on this matter. METHODS: A detailed questionnaire prepared for AE was sent to neurologists via social media and WhatsApp after the approval of the Ethics Committee. The responses of 245 respondents working in different settings were analyzed, and the group with 15 years or less experience in neurology was statistically compared to the group with more than 15 years of experience. RESULTS: Awareness and knowledge levels on AE seemed high in all groups, while 11% had never thought about AE during the differential diagnosis in real life. Before starting treatment, 20% thought that the autoantibody result should definitely support it, and 77.6% reported that they did not recognize AE well. Participants stated that satisfactory guidelines for diagnosis and treatment (88.2%) and widespread laboratory support (83.7%) were lacking. Neurologists with less experience and those working outside of training hospitals get more often consultation from an experienced clinician while diagnosing and conduct more detailed investigations at the diagnosis stage (p = 0.0025, p = 0.0001). CONCLUSION: This first survey study conducted in a large group of neurologists on the attitudes for the concept of AE suggested that postgraduate education, and diagnostic and treatment guidelines should be organized and antibody screening tests need to be better disseminated.

Decline of humoral immune responses after natural SARS-CoV-2 infection can be efficiently reversed by vaccination.

Our aim was to analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody level kinetics after coronavirus disease 2019 (COVID-19) infection and determine the efficiency of vaccination on SARS-CoV-2-specific antibody levels. The study included 50 SARS-CoV-2 infected and 70 uninfected cases. Levels of SARS-CoV-2-specific IgG nucleocapsid protein (IgG-NP), IgG spike protein (IgG-SP), IgM nucleocapsid protein (IgM-NP), and IgA spike protein (IgA-SP) antibodies were evaluated by an enzyme-linked immunosorbent assay in sera obtained at baseline, 1st, 3rd, and 6th month follow-up visits for infected cases and at postvaccination visits for all cases. In symptomatic cases (n = 50), IgG-SP levels were decreased in 6 months compared with baseline, while IgA-SP levels were significantly increased. IgG-NP levels were significantly decreased in symptomatic cases at the 6-month visit. After vaccination, IgG-SP levels were increased in symptomatic cases compared with prevaccination levels. Among subjects vaccinated with CoronaVac (the Sinovac COVID-19 vaccine), infected cases had approximately double the IgG-SP level of uninfected cases. SARS-CoV-2-specific antibody levels were higher at the baseline in symptomatic cases. Nevertheless, all infected cases showed significantly reduced IgG-SP levels at the 6th month. Vaccination effectively increased IgG-SP levels.

Increased serum citrullinated histone H3 levels in COVID-19 patients with acute ischemic stroke.

Background and purpose: Prevalence of acute ische-mic stroke (AIS) is increased in patients with coronavirus disease 2019 (COVID-19). A proposed hypothesis is increased virus-induced propensity to hypercoagulation resulting in arterial thrombosis. Our aim was to provide evidence regarding the involvement of neutrophil extracellular trap (NET) formation (NETosis) in COVID-19 related AIS. Methods: Twenty-six consecutively enrolled COVID-19+ pneumonia patients with AIS, 32 COVID-19+ pneumonia patients without AIS and 24 AIS patients without COVID-19 infection were included to the study. Clinical characteristics of recruited patients were collected. Serum levels of citrullinated histone H3 (H3Cit; a factor of NETosis), IL-8 and C5a (mediators associated with NETosis) were measured by ELISA (enzyme-linked immunosorbent assay). Results: H3Cit levels were significantly higher in COVID-19+ AIS patients, whereas all study groups showed comparable IL-8 and C5a levels. There were no significant differences among etiological subgroups of AIS patients with or without COVID-19. AIS patients with COVID-19 showed relatively increased white blood cell, lymphocyte, neutrophil, D-dimer, C-reactive protein and procalcitonin levels than control groups. H3Cit levels did not correlate with clinical/prognostic features and inflammation parameters. H3Cit and IL-8 levels were correlated in COVID-19 patients without stroke but not in COVID-19 positive or negative AIS patients. Conclusion: Increased levels of inflammation parameters and H3Cit in COVID-19 related AIS suggest that NETosis may cause susceptibility to arterial thrombosis. However, H3Cit levels do not correlate with clinical severity measures and inflammation parameters diminishing the prognostic biomarker value of NETosis factors. Moreover, the link between IL-8 and NETosis appears to be abolished in AIS.

Fingolimod impairs inactivated vaccine (CoronaVac)-induced antibody response to SARS-CoV-2 spike protein in persons with multiple sclerosis.

BACKGROUND: The impact of disease-modifying treatments on humoral response induced by inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is understudied. METHODS: We recruited 34 persons with multiple sclerosis (MS) under fingolimod treatment and 25 healthy individuals. Anti-SARS-CoV-2 spike IgG indices were measured by ELISA in sera of participants after CoronaVac vaccinations. RESULTS: Persons with MS displayed significantly lower antibody levels and seropositivity prevalence. Persons with MS with longer fingolimod treatment durations displayed lower anti-SARS-CoV-2 indices. CONCLUSION: Our results support previous findings regarding humoral response impairing effect of fingolimod after vaccinations. Patients under fingolimod treatment may require closer monitoring for COVID-19.