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.

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.

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.

Evaluation of Patients with Suspicion of COVID-19 in Pediatric Emergency Department.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) have different clinical presentations in children. Most symptomatic children with suspicion of COVID-19 have fever and respiratory symptoms. In this retrospective study, we aimed to describe demographic features, clinical characteristics, and outcomes of confirmed and probable COVID-19 patients admitted to our pediatric emergency department (ED). METHODS: We identified 135 children (aged 1 month-18 years) with suspicion of the COVID-19 who were admitted to our ED between March 11 and May 12, 2020. The urgency of patients was evaluated according to their Pediatric Assessment Triangle (PAT) and Emergency Severity Index (ESI) scores. Patients were divided into two groups as confirmed cases (Group 1) and probable cases (Group 2). Clinical, laboratory, radiologic features, and the disease severity of patients were analyzed. RESULTS: According to PAT evaluation, 82 patients (65.6%) were non-urgent. The most frequent ESI triage category level was 3 (n=102, 76.1%). Forty-one (30.4%) patients were identified as laboratory-confirmed cases. Fifty-five (40.7%) patients were between 28 days and 4 years of age. Fever with cough was the most frequent symptoms at the onset of illness in COVID-19 positive patients (n=16, 39%). Sixty-four (47.4%) patients had mild disease and 40 (29.6%) patients had comorbidities. In Group 1, neutropenia was significantly higher than Group 2 (p=0.024). Mean procalcitonin and erythrocyte sedimentation rate levels of Group 2 were significantly higher than Group 1 (p=0.012 and p=0.028, respectively). Twenty-eight of 51 patients had chest computed tomography findings which were compatible with COVID-19. Fifty-one (37.8%) patients were discharged from ED, 81 (60%) were admitted to the ward, and 3 (2.2%) were admitted to the pediatric intensive care unit. CONCLUSION: During our study, we confirmed the diagnosis of 45 of 135 probable cases with the SARS-CoV-2 polymerase chain reaction test. Among confirmed COVID-19 cases, most of our patients had mild or moderate disease. The clinic of only confirmed three patients was classified as severe disease, and we had no critically ill patient.