Differentially induced immunity in buccal and nasal mucosae after vaccination for SARS-CoV-2: Prospects for mass scale immunity-screening in large populations.

Introduction: Humoral immunity after SARS-CoV-2 vaccination has been extensively investigated in blood. Aim of this study was to develop an ELISA method in order to determine the prevalence of IgG and IgA SARS-CoV-2 domain 1 spike-protein (S) specific antibodies (Abs) in buccal and nasal mucosal surfaces of vaccinees. Methods: To this end, we analyzed 69 individuals who received their first vaccine dose between February and July 2021. Vaccines administered were BNT162b2, mRNA-1273 or ChAdOx1-nCoV-19. Detection of IgG and IgA Abs was performed using commercial ELISA kits for both blood and swab samples after protocol modification for the latter. Results: Anti-spike IgG and IgA Abs in the buccal and/or nasal swabs were detectable in >81% of the study subjects after the second dose. The IgG measurements in buccal swabs appeared to correlate in a more consistent way with the respective measurements in blood with a correlation coefficient of r=0.74. It is of note that IgA Abs appeared to be significantly more prevalent in the nasal compared to the buccal mucosa. Optimal selection of the assay cut-off for the IgG antibody detection in buccal swabs conferred a sensitivity of 91.8% and a specificity of 100%. Last, individuals vaccinated with mRNA-based vaccines exhibited higher antibody levels in both blood and mucosal surfaces compared to those receiving ChAdOx1-nCoV-19 confirming previously reported results. Conclusion: In conclusion, our findings show a differential prevalence of anti-S Abs on mucosal surfaces after vaccination for SARS-CoV-2, while they also set the basis for potential future use of IgG antibody detection in buccal swabs for extended immunity screening in large populations.

Adaptive immunity to SARS-CoV-2 infection: A systematic review.

Background: There is evidence that the adaptive or acquired immune system is one of the crucial variables in differentiating the course of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This work aimed to analyze the immunopathological aspects of adaptive immunity that are involved in the progression of this disease. Methods: This is a systematic review based on articles that included experimental evidence from in vitro assays, cohort studies, reviews, cross-sectional and case-control studies from PubMed, SciELO, MEDLINE, and Lilacs databases in English, Portuguese, or Spanish between January 2020 and July 2022. Results: Fifty-six articles were finalized for this review. CD4+ T cells were the most resolutive in the health-disease process compared with B cells and CD8+ T lymphocytes. The predominant subpopulations of T helper lymphocytes (Th) in critically ill patients are Th1, Th2, Th17 (without their main characteristics) and regulatory T cells (Treg), while in mild cases there is an influx of Th1, Th2, Th17 and follicular T helper cells (Tfh). These cells are responsible for the secretion of cytokines, including interleukin (IL) - 6, IL-4, IL-10, IL-7, IL-22, IL-21, IL-15, IL-1α, IL-23, IL-5, IL-13, IL-2, IL-17, tumor necrosis factor alpha (TNF-α), CXC motivating ligand (CXCL) 8, CXCL9 and tumor growth factor beta (TGF-ß), with the abovementioned first 8 inflammatory mediators related to clinical benefits, while the others to a poor prognosis. Some CD8+ T lymphocyte markers are associated with the severity of the disease, such as human leukocyte antigen (HLA-DR) and programmed cell death protein 1 (PD-1). Among the antibodies produced by SARS-CoV-2, Immunoglobulin (Ig) A stood out due to its potent release associated with a more severe clinical form. Conclusions: It is concluded that through this study it is possible to have a brief overview of the main immunological biomarkers and their function during SARS-CoV-2 infection in particular cell types. In critically ill individuals, adaptive immunity is varied, aberrantly compromised, and late. In particular, the T-cell response is also an essential and necessary component in immunological memory and therefore should be addressed in vaccine formulation strategies.

BNT162b2 mRNA Vaccine-Induced Immune Response in Oral Fluids and Serum.

OBJECTIVES: The COVID-19 vaccine is currently being administered worldwide to address the ongoing pandemic. Although these vaccines have proven effective in preventing severe disease, the level of immunity required to prevent respiratory mucosal infection remains less well understood. Therefore, it is desirable to develop a noninvasive screening strategy such as oral fluid to monitor secreted antibodies longitudinally as potential surrogates of mucosal immunity. METHODS: We evaluated the anti-spike protein antibodies in gingival crevicular fluid (GCF) and saliva and compared them to immune responses in the blood of 50 healthy health care workers following 2 doses of intramuscular Pfizer/BioNTech-BNT162b2 vaccine. RESULTS: The antibodies to SARS-CoV-2 spike and subdomain proteins (RBD, S1, S2, and NTD) were significantly higher in serum than oral fluids but showed a greater detection rate and higher median titres in GCF than saliva. For all tested SARS-CoV-2 antigens, IgG in GCF (as opposed to saliva) showed a more significant and stronger correlation with IgG in serum. Serum-neutralising antibodies (Nab) titres also displayed a significant and stronger correlation with anti-spike protein and their subdomains in GCF than saliva. Interestingly, the time post-second dose of vaccine and sex had a similar influence on IgG in serum and GCF. However, interferon (IFN)-γ-producing T-cell responses showed no association with SARS-Cov-2 IgG antibodies in serum, GCF, or saliva and neutralisation antibodies in serum. The correlation matrix of all measured parameters grouped serum and GCF IgG parameters separately from salivary IgG parameters indicating that GCF better represents the humoural response in serum than saliva. CONCLUSIONS: Within limitations, we propose that GCF could be a less invasive alternative to serum and more appropriate than saliva to detect antibody responses by current COVID-19 vaccines if the GCF collection procedure could be standardised. Further research is needed to investigate the suitability of GCF for community immune surveillance for vaccines.

SARS-CoV-2 evolution and patient immunological history shape the breadth and potency of antibody-mediated immunity.

Since the emergence of SARS-CoV-2, humans have been exposed to distinct SARS-CoV-2 antigens, either by infection with different variants, and/or vaccination. Population immunity is thus highly heterogeneous, but the impact of such heterogeneity on the effectiveness and breadth of the antibody-mediated response is unclear. We measured antibody-mediated neutralisation responses against SARS-CoV-2Wuhan, SARS-CoV-2α, SARS-CoV-2δ and SARS-CoV-2ο pseudoviruses using sera from patients with distinct immunological histories, including naive, vaccinated, infected with SARS-CoV-2Wuhan, SARS-CoV-2α or SARS-CoV-2δ, and vaccinated/infected individuals. We show that the breadth and potency of the antibody-mediated response is influenced by the number, the variant, and the nature (infection or vaccination) of exposures, and that individuals with mixed immunity acquired by vaccination and natural exposure exhibit the broadest and most potent responses. Our results suggest that the interplay between host immunity and SARS-CoV-2 evolution will shape the antigenicity and subsequent transmission dynamics of SARS-CoV-2, with important implications for future vaccine design.

Memory B cell development after asymptomatic or mild symptomatic SARS-CoV-2 infection.

BACKGROUND: The development of memory B cells after asymptomatic SARS-CoV-2 infection is not well understood. METHODS: We compared Spike antibody titers, pseudovirus neutralizing antibody titers, and memory B cell responses among SARS-CoV-2 PCR positive Marine recruits who either reported asymptomatic or symptomatic infection. RESULTS: 36 asymptomatic participants exhibited similar Spike IgG titers, Spike IgA titers, and pseudovirus neutralization titers compared to 30 symptomatic participants. Pseudovirus neutralization and Spike IgG titers showed significant positive correlations with frequency of memory B cells. CONCLUSIONS: Among young adults, asymptomatic SARS-CoV-2 infection induced antibody and memory B cell responses comparable to mild symptomatic infection.

Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial.

Intestinal bacteria may influence lung homeostasis via the gut-lung axis. We conducted a single-center, quadruple-blinded, randomized trial in adult symptomatic Coronavirus Disease 2019 (Covid19) outpatients. Subjects were allocated 1:1 to probiotic formula (strains Lactiplantibacillus plantarum KABP022, KABP023, and KAPB033, plus strain Pediococcus acidilactici KABP021, totaling 2 × 109 colony-forming units (CFU)) or placebo, for 30 days. Co-primary endpoints included: i) proportion of patients in complete symptomatic and viral remission; ii) proportion progressing to moderate or severe disease with hospitalization, or death; and iii) days on Intensive Care Unit (ICU). Three hundred subjects were randomized (median age 37.0 years [range 18 to 60], 161 [53.7%] women, 126 [42.0%] having known metabolic risk factors), and 293 completed the study (97.7%). Complete remission was achieved by 78 of 147 (53.1%) in probiotic group compared to 41 of 146 (28.1%) in placebo (RR: 1.89 [95 CI 1.40-2.55]; P < .001), significant after multiplicity correction. No hospitalizations or deaths occurred during the study, precluding the assessment of remaining co-primary outcomes. Probiotic supplementation was well-tolerated and reduced nasopharyngeal viral load, lung infiltrates and duration of both digestive and non-digestive symptoms, compared to placebo. No significant compositional changes were detected in fecal microbiota between probiotic and placebo, but probiotic supplementation significantly increased specific IgM and IgG against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) compared to placebo. It is thus hypothesized this probiotic primarily acts by interacting with the host's immune system rather than changing colonic microbiota composition. Future studies should replicate these findings and elucidate its mechanism of action (Registration: NCT04517422).Abbreviations: AE: Adverse Event; BMI: Body Mass Index; CONSORT: CONsolidated Standards of Reporting Trials; CFU: Colony-Forming Units; eDRF: Electronic Daily Report Form; GLA: Gut-Lung Axis; GSRS: Gastrointestinal Symptoms Rating Scale; hsCRP: High-sensitivity C-Reactive Protein; HR: Hazard Ratio; ICU: Intensive Care Unit; OR: Odds Ratio; PCoA: Principal Coordinate Analysis; RR: Relative Risk; RT-qPCR: Real-Time Quantitative Polymerase Chain Reaction; SARS-CoV2: Severe acute respiratory syndrome coronavirus 2; SpO2: Peripheral Oxygen Saturation; WHO: World Health Organization.

The comparison of SARS-CoV-2 antibody levels in medical personnel induced by different types of vaccines compared to the natural infection

INTRODUCTION: During the last two and a half years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread around the world. Most of the SARS-CoV-2 vaccines are designed to produce anti-SARS-CoV-2 immunoglobulin G (IgG) against the viral S-glycoprotein. The aim of this study was to measure the anti-S antibody titres among the medical personnel who had been fully vaccinated with different types of vaccines, and to compare them with those who were COVID-19 convalescents. MATERIAL AND METHODS: In this study serum was collected from 261 healthcare workers, of whom 227 were vaccinated, while 34 were recovered participants who were not immunised. Serum samples were collected 21 days after the first dose and 60 and 180 days after the second dose of the vaccines and tested with a commercial ELISA kit. RESULTS: The highest antibody level (12 AU/ml) was measured in the Pfizer-BioNTech group, followed by Sinopharm (9.3 AU/ml), Sputnik V (5.9 AU/ml), Sinovac (4.6 AU/ml) and Oxford/Astra- Zeneca vaccine (2.5 AU/ml) 60 days after the second dose of the vaccines (90 days after the first dose). The seropositivity rate for mRNA vaccine was 88.5%, for vector vaccines 86.2% and for inactivated vaccines 71.4%. When comparing these antibody levels with COVID-19 convalescents, higher antibody titres were found in vaccinated participants (5.76 AU/ml vs 7.06 AU/ml), but the difference was not significant (p = 0.08). CONCLUSIONS: Individuals vaccinated with mRNA and vector vaccines had a higher seroconversion rate compared to the group vaccinated with inactivated vaccines, or convalescents. Copyright © 2023 Termedia.

Antiviral foods in the battle against viral infections: Understanding the molecular mechanism

Viruses produce a variety of illnesses, which may also cause acute respiratory syndrome. All viral infections, including COVID‐19, are associated with the strength of the immune system. Till now, traditional medicine or vaccines for most viral diseases have not been effective. Antiviral and immune‐boosting diets may provide defense against viral diseases by lowering the risk of infection and assisting rapid recovery. The purpose of this review was to gather, analyze, and present data based on scientific evidence in order to provide an overview of the mechanistic insights of antiviral bioactive metabolites. We have covered a wide range of food with antiviral properties in this review, along with their potential mechanism of action against viral infections. Additionally, the opportunities and challenges of using antiviral food have been critically reviewed. Bioactive plant compounds, not only help in maintaining the body's normal physiological mechanism and good health but are also essential for improving the body's immunity and therefore can be effective against viral diseases. These agents fight viral diseases either by incorporating the body's defense mechanism or by enhancing the cell's immune system. Regular intake of antiviral foods may prevent future pandemic and consumption of these antiviral agents with traditional medicine may reduce the severity of viral diseases. Therefore, the synergistic effect of antiviral foods and medication needs to be investigated. [ FROM AUTHOR] Copyright of Food Science & Nutrition is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

COVID-19 vaccine hesitancy and its associated factors among Health Care Workers of Islamabad

Background: Covid-19 has been declared a global pandemic by WHO. Health Care Workers (HCWs) being the front-line warriors have been most exposed to the SARS-CoV-2 virus. Vaccine hesitancy against Covid-19 has been seen among HCWs. The main aim of the research was to find the hesitancy rates of vaccine among HCWs and the pulling and pushing factors to get vaccinated. Methods: A descriptive cross-sectional study was conducted on HCWs. Questionnaires on Google forms were sent to all participants through their WhatsApp number and data was analysed through SPSS version 23.0. Results: Out of 81 HCWs selected, 51.9% (n=42) were initially hesitant when the vaccine was first introduced. The main pulling factor initially to get vaccinated was to shield loved ones, 38.75% (n=31) and 46.2% (n=37) of them received a booster dose of vaccine mainly due to employment requirements. Out of the total, 19.75% (n=16) are still hesitant even after vaccination and the most common pushing factors were fear of the side effects and inadequately tested vaccines. Conclusion: Though the majority of the HCWs got vaccinated, vaccine hesitancy is still present among the HCWs and the major reason is uncertainty about the side effects it could cause in the long term.

Assessment of concerns about vaccination among recovered COVID-19 patients in Saudi Arabia

Background: Vaccine hesitancy re-emerged as a critical public health issue during the COVID-19 pandemic. Aim(s): This study assessed the concerns of recovered COVID-19 patients about vaccination and the predictors of vaccine hesitancy. Method(s): This was a cross-sectional study of 319 adult patients who recovered from COVID-19 in Saudi Arabia. It was conducted during 1 May to 1 October 2020 at King Abdulaziz Medical City, Riyadh. Each participant was interviewed 6-12 months post-recovery using the vaccination attitude examination scale. Data were collected on COVID-19 illness severity, sociodemographic characteristics, history of chronic disease, and post-COVID-19 vaccination. Level of vaccination concern was assessed based on the percentage mean score (PMS). Result(s): Most (85.3%) of the patients who recovered from COVID-19 expressed moderate overall concern (PMS = 68.96%) about vaccination. Concern was highest for mistrust in vaccine benefits (PMS = 90.28%), followed by natural immunity preference (PMS = 81.33%) and worries about the vaccine side-effects (PMS = 60.29%). Concern over commercial profiteering was low (PMS = 43.92%). The overall PMS for concern about vaccination was significantly higher among patients aged 45+ years (t = 3.12, P = 0.002) and among those who had experienced severe COVID-19 illness (t = 1.96, P = 0.05). Conclusion(s): Overall concern about vaccination was high, and specific concerns were prevalent. Patient education on how the vaccine protects against reinfection should be targeted at COVID-19 patients before being discharged from hospital.Copyright © Authors 2023;Licensee: World Health Organization.

Can the immune system be targeted to treat COVID-19?

In COVID-19, SARS-CoV-2 has been shown to activate both innate and adaptive immune responses. However, uncontrolled or impaired immunity can lead to the development of severe forms of the disease. Understanding the underlying immunology influencing disease expression as well as the natural history of the virus is imperative to develop preventative and therapeutic strategies to tackle the COVID-19 pandemic. This chapter aims to discuss the literature surrounding the immunology of COVID-19 in a clinical context, specifically applied to the development of therapeutics and vaccines to SARS-CoV-2.Copyright © ERS 2021.

Immunology and Pathogenesis of COVID-19

The whole world is facing a pandemic situation ever since the outbreak of SARSCoV-2 in Wuhan, China in December 2019. The coronavirus disease (COVID-19) presents a wide spectrum of clinical manifestations ranging from asymptomatic to severe pneumonia-like situations followed by multisystem failure leading to the death of the individual. Studies from the past coronavirus outbreaks, the SARS, and MERS-CoV, have helped us understand the current SARS-CoV2 to a large extent. Once the host encounters the virus, an innate immune response is generated which subsequently leads to activation of the adaptive immune response to eliminate the virus. However, this immune response is misbalanced in some individuals and is the main factor causing the pathological manifestation of COVID-19. In this chapter, we have addressed the humoral and cellular immune changes induced by the virus along with the role of cytokine storm in disease progression. © The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.

Vaccine prevention of COVID-19 in the system of anti-epidemic and preventive measures. literature review

Relevance: Despite the undoubted successes achieved in the fight against infectious diseases, the importance of pathogens in human pathology not only does not decrease, but also shows a tendency to increase. Thousands of people die from complications every year. This is due to the fact that viruses, primarily influenza viruses and coronaviruses, have the ability to change their structure and the mutated virus is able to infect a person again. So, a person who has had the flu has a good immune barrier, but nevertheless a new modified virus is able to easily penetrate it, since the body has not yet developed immunity against this type of virus. To date, the most effective measure of protection against viral infections is vaccination. Aim: Analysis of literature data on the role of vaccination in the system of anti-epidemic and preventive measures in the fight against viral infections, including COVID-19. Search strategy: Scientific publications were searched in the following databases: PubMed, Medline, e-Library, using the Google Scholar scientific search engine. The search depth is 3 years. Criteria for inclusion: publications in Russian and English by thematic requests: vaccination, COVID-19, pandemic;publications included in the PubMed, Medline, e-Library databases;publications for the last 3 years. Criteria for excluding: articles with paid access;s. A total of 168 sources were found. 62 articles passed the selection algorithm, accepted for analysis. Results: Analysis of the literature data has shown that today vaccination is an effective and beneficial measure against various infections worldwide. Vaccines save millions of lives every year. The development of safe and effective vaccines against COVID-19 is a huge step forward towards ending the pandemic and returning to a normal lifestyle. Conclusions: Based on the literature review, it became known that with the help of vaccines, humanity managed to get rid of a number of dangerous infections, and today, in the confrontation with the coronavirus pandemic, great hope is placed on them. A lot of research teams in different countries have joined in the search for a reliable vaccine.

Phase 3 Study of Safety and Immunogenicity of Gbp510 Vaccine Adjuvanted with As03 in Adults

Intro: GBP510 contains the self-assembling recombinant nanoparticle displaying SARS-CoV-2 Spike protein receptor binding domain and is adjuvanted with AS03. We report interim Phase 3 study (NCT05007951) results up to 4 weeks post-dose 2 (Data-cut: March-18-2022), where immunogenicity to the D614G ancestral strain and safety of 25mug GBP510/AS03 candidate was compared to ChAdOx1-S (Vaxzevria). Method(s): This Phase 3 randomized, active-controlled, observer-blind, parallel- group study in adults was conducted in 6 countries. Cohort1: 1,895 subjects (naive to COVID-19 vaccination and infection) randomized at 2:1 ratio (GBP510/AS03:ChAdOx1-S) to assess immunogenicity and safety;Cohort 2: 2,141 subjects at 5:1 ratio, regardless of their serostatus at screening for safety assessment. Subjects were vaccinated twice at a 4-week interval with 0.5 mL of the test vaccine (GBP510/AS03) or active control (ChAdOx1-S) in deltoid muscle. The primary objective was to demonstrate the superiority of geometric mean titer (GMT) and non-inferiority in seroconversion rate (SCR: >=4-fold rise from baseline) of neutralizing antibodies over ChAdOx1-S by live-virus neutralization assay (FRNT). Finding(s): At 2 weeks post-dose 2, GMT ratio of the two groups (Test vaccine/Active control) was 2.93 [95% CI: 2.63, 3.27], satisfying the hypothesis of superiority (95% CI lower limit> 1). The SCR difference (Test vaccine - Active control) was 10.76% [95% CI: 7.68, 14.32], satisfying the hypothesis of non- inferiority (95% CI lower limit> -5%). Good cell-mediated immune responses for Th1 cytokines were also observed with the test vaccine (FluoroSpot). The AE incidence rate for the test vaccine was higher than the active control for solicited local AEs (56.69% vs 49.20%), and comparable for solicited systemic AEs (51.21% vs 53.51%) and unsolicited AEs (13.34% vs 14.66%) after any vaccination. Conclusion(s): Higher immune responses were observed with GBP510/AS03 compared to ChAdOx1-S against D614G strain after 2 weeks post-dose 2. GBP510/AS03 showed a clinically acceptable safety profile;no safety concerns were identified during the study period.Copyright © 2023

Six months follow-up study on health care workers on persistence of antibodies to SARS-CoV-2 after covishield vaccination

BACKGROUND: Efficacy of COVID vaccines has been evaluated in various studies. The interim analysis from four randomized controlled trials in UK, Brazil, and south Africa regarding efficacy of two doses of the vaccine was found to be 70.4% (95.8% CI 54.8-80.6). There is a limited data on follow-up Ab titer post vaccination. Hence, the current study is first of its kind with the objective to determine vaccine long term efficacy and its determinants. METHODS: Health Care Workers (HCW) from Apollo Multispeciality Hospitals, Kolkata who underwent Covishield vaccination from January 2021 to April 2021 were included in the study. Serological testing was done prior to first and second dose of vaccinations, and additionally around six months post second dose. RESULTS: Between January 2021 to April 2021, 2032 HCW, with predominant age of less than 30 years (44.83%) and male gender (61.96%) undergoing Covishield vaccination were enrolled. Antibodies were detected in 953 (46.9%) individuals prior to first dose, 1449 out of 1495 (96.9%) remained positive prior to second dose and 465 out of 504 (92.3%) HCW after 6 months and remaining 39 (7.7%) either had lost or never had antibodies in their blood. The mean +or- SD value of first, second and third antibodies were 2.35 +or- 3.10, 10.46 +or- 4.84 and 8.75 +or- 4.88 respectively. CONCLUSIONS: This study provides long observation period, covering the complete progress of the pandemic which provides a "real-life" picture of the antibody level dynamics over time, and after vaccination.

Stability and Hopf bifurcation analysis of a delayed SIRC epidemic model for Covid-19

This paper examines the spread of COVID-19 during the pandemic using the SIRC model and transmission delay. We investigated both the infection-free (E-0) and the infected (E-1) steady states are locally stable. We evaluated the duration of the delay for which the steadiness pursues to be maintained, by the Nyquist criterion. The Hopf bifurcation is used to explain the nature of the disease at the start of a 2nd cycle and the kinds of interventions needed to end it. Theoretical results are supported through numerical simulations.

Immune Responses to Mrna Vaccines against Sars-Cov2 in Patients with Immune-Mediated Inflammatory Rheumatic Diseases

Background/Aims Patients with immune-mediated rheumatic diseases (IMRD) are commonly treated with immunosuppressors and are prone to infections. Recently introduced mRNA SARS-Cov2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-We aim to fully characterize B and T cell immune responses elicited by mRNA SARS-Cov2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccine's immunogenicity. Methods Humoral, CD4 and CD8 immune responses were investigated in 147 SARS-Cov2-naive patients with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-Cov2 mRNA vaccine. Responses were compared with age, gender, and diseasematched IMRD patients not receiving immunosuppressors and with healthy controls Results IMRD patients showed decreased seroconversion rates (63% vs 100%, p=0.04) and cellular immune responses (59% vs 100%, p=0.007). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept deeply affected humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed severely impaired humoral responses but cellular responses were often preserved. Antibody titers were reduced with mycophenolate and azathioprine but preserved with leflunomide. Conclusion IMRD patients exhibit impaired SARS-CoV-2 vaccine-immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show the most deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine's immunogenicity.

An Immunocompetent Adult With Adenovirus Hepatitis

Introduction: In the US there has been a recent outbreak of adenovirus hepatitis in the pediatric population. However, to our knowledge, there has been only one reported case of adenovirus hepatitis in an immunocompetent adult. We have identified another such case. Case Description/Methods: A 25 year old female with no medical history presented with abdominal pain, nausea, vomiting, diarrhea, and subjective fevers for two weeks and was found to have transaminitis 25-30x the upper limit of normal, which were: AST 791, ALT 542, ALP 92, and total bilirubin of 2.9. The patient reported no prior history of liver disease. She denied alcohol, tobacco, illicit drugs, or herbal medications, but did report taking acetaminophen 1500 mg daily for two weeks. Serum acetaminophen levels were normal and serum and urine toxicology were negative. US with doppler was unremarkable, CT showed cholelithiasis, MRCP showed a normal common bile duct without obstructive calculus. Autoimmune causes of hepatitis, ceruloplasmin and alpha-1 antitrypsin were all unremarkable. HAV, HBV, HCV, HDV, HEV, CMV, HSV, VZV, EBV, HIV, and COVID19 were all negative. Ultimately, the serology for adenovirus was positive. After a week of supportive treatment, the patient's labs trended down and symptoms resolved. Discussion(s): Adenovirus is confirmed by a rise in antibody titer or by virus detection. Coagulative necrosis in histopathology is a finding in liver biopsies if they are pursued in unexplained cases of liver injury. Ultimately, adenovirus hepatitis can be diagnosed once all common causes of hepatitis have been excluded. In the current outbreak, only children have been getting adenovirus hepatitis. In adults, a high prevalence of neutralizing antibodies contributes to immunity, and therefore only in immunocompromised states, do adults get such an infection. Supportive care with IV fluids, electrolyte correction, and antiemetics usually is enough with eventual symptomatic and laboratory improvement as it was for our patient. Studies have shown that extensive disease can be treated with antiviral drugs, cidofovir, and ribavirin. Our patient's history of acetaminophen use is a confounder, however, her normal serum level and her symptoms suggestive of an infectious cause made acetaminophen less of a culprit. We hypothesize that our patient's use of acetaminophen when she was initially exposed to the virus is what made her susceptible to developing adenovirus hepatitis and we hope this case adds insight for clinicians dealing with future adult cases.

Investigation on the risk factores for mortality of patients with COVID-19 and prioritization these factores using neural network in some southern cities of Iran

Background & Aims: Epidemics of human viruses began during the period of Neolithic around 12,000 years ago. Humans developed more densely population which allowed viruses to spread rapidly among communities. Also, plant and livestock viruses increased along with human viruses (2). At the January 2020, the coronavirus disease (COVID-19 7th human coronavirus) was discovered in Wuhan, Hubei province of China. COVID-19 virus caused six million deads in the world to date and cussed infection of more than seven million of cases in Iran (1). This infectious disease caused by the SARS-CoV-2 virus. This virus was contagious and fast-spread. Despite the aquarantine politics, SARS-CoV-2 virus caused many permanent economic and health damages in most countries. Coronaviruses are positive-sense, single- stranded enveloped RNA viruses with helical capsids that infect a wide range of hosts including humans, bats, other mammals, and birds (2). Coronaviruses are belonging to Nidovirales order, Coronaviridae family, Coronovirinae subfamily and four genera of alpha, beta, delta, and gamma. Alpha and beta coronaviruses are known as human infection agents. SARS-COV-2 virus abilities are including: high mortality number, short period of incubation, widespread transmission protocols, asymptomatic infection and affecting on most vital organs (heart, brain, lungs and ...) which have attracted the health system attention and caused neglect to the other chronic and non-communicable diseases (4). Therefore, the disease incidence, prevalence and prioritization around the world may change in the future. From the beginning of COVID-19 pandemic, some symptoms and risk-factors have been introduced to the world as the increase elements of morbidity and mortality. Studies have shown that having any kind of underlying diseases and risk factors will be effective in the COVID-19 disease severity and mortality (6). Some of these important risk factors are including of chronic kidney disease, hypertension, age, gender, obesity, obstructive pulmonary diseases, diabetes, lung diseases, cardiovascular diseases, cancer, and liver disease. Also, each risk factors have different impact in different geographic areas (7). Some factors, such as different viral load kinetics in each individual person, epidemiological history, therapeutic or pharmacological effects and immune response have some major impacts on the laboratory diagnostic results. Due to the successive mutations of the SARS-CoV-2 virus and the high incidence disease, it seems that the vaccination alone cannot prevent the COVID-19 (9). On the other hand, the World Health Organization has warned about the vaccination as the only pandemic control protocol. Therefore, the prevalence of morbidity and mortality have become the public health concerns in the world since the beginning of the COVID-19 epidemic and the vaccination. Recognizing of the risk-factors and symptoms on COVID-19 in different geographic areas can be a helpful source to prevent the mortality. Understanding risk factors can help the world to control of the coronaviruses pandemic period and similar situations in the future. Therefore, the aim of this study was to determine the risk-factors of mortality of COVID-19 patients in three cities of Khuzestan province, Iran. Methods: This research was an analytical cross-sectional study. Some details of 27963 COVID-19 patients such as clinical symptoms, individual characteristics and underlying diseases were gathered from hospitals in Abadan, Shadegan and Khorramshahr cities in Khuzestan province, Iran, from 20 February 2020 to November 2020. All the under-study population was previously investigated in terms of COVID-19 infection by the medical examinations and laboratory methods. This under-study population was categorized into three different groups such as hospitalized, outpatients and dead patients. Hospitalized patients have admitted in general or ICU (Intensive Care Unit) sector. Obtained database of COVID-19 patients was analyzed by IBM SPSS version 22.0 under regression, logistic model (u

Clinical and immunological parallels in children patients with COVID-19

The problem of the incidence of new coronavirus infection in childhood is becoming increasingly important. At the same time, questions arise regarding the peculiarities of the pathogenesis of COVID-19 in children. The aim of the research was to study the clinical and immunological features of COVID-19 in children hospitalized with a severe course of the disease. Material and methods. We examined 53 children from 0 to 15 years old, hospitalized with suspected new coronavirus infection at Children's Clinical Hospital No. 3 in Novosibirsk from October to December 2020. Determination of specific IgM and IgG antibodies to SARS-CoV-2 antigens in serum blood was carried out using the ELISA method. SARS-CoV-2 virus RNA in nasopharyngeal and oropharyngeal swabs was determined using commercial kits for PCR diagnostics. A z-test was used to compare relative numbers. The significance level was taken equal to 5% (p=0.05). Results and discussion. All examined children hospitalized with suspected COVID-19, regardless of the duration of the disease, had specific IgG antibodies to SARS-CoV-2 antigens, which confirms earlier contact with the new coronavirus in relation to the time of the examination. In 63.6% of cases, specific IgM antibodies of the class to SARS-CoV-2 were detected in the blood serum, in 6% of cases the result was doubtful. IgM antibodies were not detected in blood serum in 30.3% of patients. The results obtained for the determination of IgG and IgM antibodies to SARS-CoV-2 antigens may reflect the atypical nature of seroconversion in COVID-19. An extremely diverse clinical symptomatology was revealed, including, in addition to catarrhal syndrome and intoxication syndrome, abdominal, meningeal, and articular syndromes. In 24.3% of children, polymorphic exanthema was detected, which may be a manifestation of the systemic nature of damage to the vascular wall. Conclusion. With serologically confirmed SARS-CoV-2 etiology of the infectious process in the examined children, an extremely diverse clinical symptomatology was revealed, which, most likely, may be associated with multiple organ damage.Copyright © Transplantologiya. The Russian Journal of Transplantation.All right reserved.