Omicron driven ECMO in a vaccinated critically ill patient

Objectives: Reporting a case of a COVID-19 vaccinated patient admitted to our intensive care unit with severe acute respiratory failure due to SARSCoV2 - Omicron variant, rapidly deteriorating requiring intubation, prone ventilation, and ECMO support. Method(s): A 62 years old Caucasian male was admitted in ICU for rapidly deranging respiratory failure and fever which occurred over the previous 24h. The patient received two doses of SARS-CoV2 vaccine (Oxford, AstraZeneca), the last one over five months before onset of symptoms. The patient was admitted to the intensive care unit (ICU) with tachypnea, low peripheral saturation (80%), elevated serum creatinine (2.4 mg/dl), and mild obesity (BMI 34,6). Pressure support ventilation trial (2 hours) failed carryng out to orotracheal intubation and protective ventilation. Worsening of respiratory exchanges (5 th day from the admission) required a rescue prone ventilation cycle, in the meantime an indication was given to the placement of veno-venous ECMO. The cannulation site was femoro-femoral and the configuration used was Vivc25- Va21, according to the current ELSO nomenclature;ECMO flow was progressively increased until a peripheral saturation of 95% was obtained. Result(s): The patient passed out after 2 month of extracorporeal support with no sign of recovery of pulmonary and renal function. Conclusion(s): Unlike evidences showing a lower symptomatic engagement of the Omicron variant SARSCoV2 positive patients, we have witnessed a rapid and massive pulmonary involvement. The short time that passed from the onset of symptoms and the rapid decay of respiratory function required rapid escalation of the intensity of care up to extracorporeal support. The patient showed previous pathologies that can lead to suspicion of a loss of immune coverage given by the vaccine, in addition to the long time elapsed since the last dose. (Figure Presented).

Effects of Covid-19 Vaccines on Mental Health of an Individual A Cross-Sectional Clinical Study

Objective: The mains and objectives of the study was to evaluate the impact of Covid'19 vaccination on mental health status. Study Design: A Cross-Sectional Clinical Study. Place and Duration: It is a cross-sectional study which was conducted by the house officers and the faculty of Dow International Dental College from june2022 to January 2023. Methodology: This study was conducted by distributing the questionnaire among the patients coming to the Outpatient Department at Dow International Dental College. A total of 280 Questionnaires were filled among the Vaccinated Patients coming to the OPD. Questions were inquired related to demographics, dosage, history, last dose, and benefit of vaccine, depression, sleep deprivation, feeling low, trouble concentrating and suicidal thoughts. The consent to fill this questionnaire by the patient was taken by 'Implied Consent'. It was in English language but was translated in Urdu by the house officers whenever it was needed to ensure the comprehension of the questions to the patients. The filled questionnaire was collected by the house officers of the dental department. A total of more than 280 questionnaires were distributed among the participants out of which 250 questionnaires were filled correctly giving us a response rate of 89.2% and dropouts of 10.8%. Practical Implications: The results of this cross-sectional clinical study have practical implications for the wider community. Encouraging Covid-19 vaccination can have a positive impact on both physical and mental health, and promoting vaccine uptake may lead to improved mental health outcomes for individuals. Such benefits can reduce the overall burden of mental health issues during the pandemic, which is beneficial to the community. Thus, public health campaigns should focus on the potential positive effects of Covid-19 vaccines on mental health to improve community well-being and promote vaccine acceptance. Result(s): Approximately 48% women and 52% male have anxiety, depression or either disorder, respectively. Adults with anxiety and depression were more likely to have low educational attainment, low household income, lack of health insurance and either lack or delay medical care. The filled questionnaire was collected by the house officers of the dental department. A total of more than 280 questionnaires were distributed among the participants out of whom 250 questionnaires were filled correctly giving us a response rate of 89.2% and dropouts of 10.8%. There was a common mental impact that was noticed and brought about people's mental health at stake. Conclusion(s): Forceful vaccination has a potential to affect mental health of an individual. Further studies are required to extrapolate the findings of the present study.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

COVID-19 Vaccination during Pregnancy: A Structured Electronic Medical Record Data Study

Objectives: To compare pregnancy loss rates, preterm birth rates and gestational age at delivery in women vaccinated against COVID-19 during pregnancy vs. those unvaccinated. Method(s): Data were captured from Dorsata Prenatal, an electronic medical record (EMR) system that captures obstetrical data for tens of thousands of pregnancies annually. Patients who delivered between February 11, 2021-June 2, 2022, were included. The vaccinated group included women who had at least one COVID-19 vaccination documented in their EMR between 30 days prior to pregnancy and delivery. The unvaccinated group included women without a COVID-19 vaccination documented. The primary outcome measure was gestational age (GA) at delivery. We analyzed the data using chi-square tests, with significance set at p<0.01. Result(s): A total of 51,994 pregnant women were identified-7,947 (15.3%) in the vaccinated group and 44,047 (84.7%) in the unvaccinated group. Vaccination rate varied by race (Asian: 19.7%;White: 17.3%;Black: 11.2%, P<0.001), ethnicity (Latino: 8.6%;Not-Latino: 18.7%;P<0.001), marital status (Married: 19.2%;Single: 8.8%;P<0.001), mother's age (>=35 years: 20.0%;<35 years 14.2%;P<0.001), and region (Northeast: 19.2%;South: 15.2%;West: 9.1%;P<0.001). The vaccinated group had significantly lower rate of preterm delivery (Gestational Age [GA]<37 weeks;vaccinated: 7.8% vs. unvaccinated: 9.6%;P<0.001), and significantly lower rates of pregnancy loss (GA<20 weeks;vaccinated: 1.1% vs. unvaccinated: 4.1%;P<0.001). Conclusion(s): This is one of the largest real-world studies to date in women who received the COVID-19 vaccination during pregnancy. Vaccination rates varied significantly across race/ethnicity. Vaccinated patients had lower preterm delivery and pregnancy loss rates compared with unvaccinated patients.Copyright © 2023

Sensitizing breast cancers to immune checkpoint inhibitors through CD27 agonism and vaccination against tumor-associated antigen

Project objective: Despite the recent revolution in immune checkpoint inhibitors (ICIs), only modest improvement in overall survival and likely caused by not enough potent cellular immunity among BC patients. Our lab has been focus on inducing cellular immunity against HER2+ BC through vaccination against the tumor-associated antigen HER2. Approximately 20 years ago, we performed an experimental pilot study by administrating HER2 peptide and recombinant protein pulsed dendritic cells (DC vaccine) to six patients with refractory HER2+ advanced or metastatic (stage II (>= 6 +LN), III, or stage IV) BC. We followed the patients on 2019 found that all of the six patients were still alive, 18 years after vaccination. Their blood sample were analyzed with cytometry by time-offlight (CyTOF) and found there is a significantly increased presence of CD27 expressing memory T cells in response to HER2 peptide stimulation. Recent report on the SARS-CoV2 mRNA vaccine also suggested that CD27 expressing memory T cells plays a critical role in long-lasting cellular immunity against SARS-CoV2 infection. Therefore, we hypothesized that CD27 plays a critical role in cellular immunity against BC, and the stimulation of CD27 expressing T cells with mAb targeting CD27 significantly increase the cellular immunity triggered by vaccination against tumor-associated antigen. Result(s): We recapitulate the rise of CD27+ antigen specific T cells among the vaccinated patients using a transgenic mouse model expressing human CD27. When combined the adenoviral-vector based HER2 (Ad-HER2) vaccination with a single dose of human aCD27 antibody (Varlilumab), we found there is a robust increase in the HER2 specific T cells compared to vaccination alone, especially CD27+CD44+ memory CD4 T cells, even after 120 days post vaccination. Using an ICIinsensitive syngeneic HER2+ BC models, we found 50% of mice in the combination group of aCD27 antibody plus Ad-HER2 showed total tumor regression by the end of study. When combined with anti-PD1 antibody, the combination of AdHER2 and Varlilumab leads to total tumor regression in 90% of tumor bearing mice with syngeneic HER2+ BC, indicating that the vaccination against tumor associated antigen HER2 plus anti-CD27 antibody sensitized ICI-insensitive HER2+ BC toward ICI. Conclusion(s): Our data demonstrates that the administration of anti-CD27 antibody significantly increase the long term presence of CD27+ antigen specific memory T cells after vaccination against tumor associated antigen HER2. As consequence, combination of anti-CD27 with HER2 sensitized the immune unresponsive breast cancer toward anti-PD1 antibody. Our study suggests that the vaccination against tumor-associated antigen with mAb targeting CD27 leads to the robust cellular immunity, which is required for successful ICIs against breast cancer.

Production and characterisation of a SARSCoV-2 S-protein RBD homodimer with increased avidity for specific antibodies.

Monitoring of the proportion of immune individuals and the effectiveness of vaccination in a population involves evaluation of several important parameters, including the level of virus-neutralising antibodies. In order to combat the COVID-19 pandemic, it is essential to develop approaches to detecting SARS-CoV-2 neutralising antibodies by safe, simple and rapid methods that do not require live viruses. To develop a test system for enzyme-linked immunosorbent assay (ELISA) that detects potential neutralising antibodies, it is necessary to obtain a highly purified recombinant receptor-binding domain (RBD) of the spike (S) protein with high avidity for specific antibodies. The aim of the study was to obtain and characterise a SARSCoV-2 S-protein RBD homodimer and a recombinant RBD-expressing cell line, as well as to create an ELISA system for detecting potential neutralising antibodies. Material(s) and Method(s): the genetic construct was designed in silico. To generate a stable producer cell line, the authors transfected CHO-S cells, subjected them to antibiotic pressure, and selected the optimal clone. To isolate monomeric and homodimeric RBD forms, the authors purified the recombinant RBD by chromatographic methods. Further, they analysed the activity of the RBD forms by Western blotting, bio-layer interferometry, and indirect ELISA. The analysis involved monoclonal antibodies GamXRH19, GamP2C5, and h6g3, as well as serum samples from volunteers vaccinated with Gam-COVID-Vac (Sputnik V) and unvaccinated ones. Result(s): the authors produced the CHO-S cell line for stable expression of the recombinant SARS-CoV-2 S-protein RBD. The study demonstrated the recombinant RBD's ability to homodimerise after fed-batch cultivation of the cell line for more than 7 days due to the presence of unpaired cysteines. The purified recombinant RBD yield from culture broth was 30-50 mg/L. Monomeric and homodimeric RBD forms were separated using gel-filtration chromatography and characterised by their ability to interact with specific monoclonal antibodies, as well as with serum samples from vaccinated volunteers. The homodimeric recombinant RBD showed increased avidity for both monoclonal and immune sera antibodies. Conclusion(s): the homodimeric recombinant RBD may be more preferable for the analysis of levels of antibodies to the receptor-binding domain of the SARS-CoV-2 S protein.Copyright © 2023 Authors. All rights reserved.

SARS-CoV2 infection after vaccination in patients requiring extracorporeal life support: An analysis from the EuroECMO-COVID study group

Objectives: At the beginning of the pandemic, it was believed that severe SARS-CoV2 infection would induce lifelong immunity and that reinfections would be unlikely. However, several cases of reinfection were documented in previously infected patient and the waning humoral immunity has raised significant concerns. Accordingly, long-term and durable vaccineinduce antibody protection against infection have also become a challenge, as several breakthroughs of COVID-19 have been identified in individuals partially or fully vaccinated. This study describes the incidence, the characteristics of severe COVID-19 infections requiring ECMO occurred after vaccination and the presence of side effects related to the vaccine. Method(s): EuroECMO COVID is a prospective, multicenter, observational study, developed by the EuroELSO, based on data from patients aged >=16 years who received ECMO support for refractory COVID-19 during the pandemic in 204 centers. The analysis investigates the survival of vaccinated patient, the associations between management-related variables, the incidence of vaccination during the different pandemic phases, the type of vaccines and the possible side effects. Result(s): Immunosuppressed patients are susceptible to reinfection even after being naturally infected or receiving a full vaccination. Ineffective antibody production, due to relatively ineffective vaccines, inadequate number of doses or the time after vaccination are involved in the pathogenesis of postvaccination infections. This population was found to have a partial immunity due to an inadequate number of doses and an overlapped time from vaccination and SARS-CoV2 incubation with PCR results after being vaccinated. Several manifestations of SARS-CoV2 infection are similar to vaccine-induce side effects and mild symptoms can be presented both as an adverse reaction after vaccination and a result of infection. In this subgroup no side effects were attributable to the vaccine. Conclusion(s): Vaccination does not entirely prevent SARS-CoV2 but will lead to less morbidity and mortality, as demonstrated by less need of ICU and ECMO care. In addition, the partial immunity for inadequate doses of vaccine or through the evolution of new variants demonstrated the importance of further analysis to differentiate the possible causes of waning humoral immunity.

Frequencies of Adverse Events Aftervaccination for Covid-19 in Patients with Systemic Lupus Erythematosus from a Reference Center in Asuncion, Paraguay

Objectives: The objective of this study was to determine the frequency of adverse effects (AE) of vaccination against COVID-19 in patients with SLE who visit medical centers in Asuncion, Paraguay. Method(s): The study performed was observational, transverse, descriptive. 152 patients with SLE were included, who received at least one dose of anti-COVID vaccine. A survey was carried out, which allowed the data collection through phone calls or instant messaging. Each investigator had a spreadsheet that related the generated code with the surveyed patient's name. Once the call ended and if the patient agreed to participate in the study, a code was generated. Result(s): 88.5% of the individuals were female, the average age was 33.93 +/- 11,102 years. Of these, 94.3% received their first dose, 86.3% the second dose, 39.7% the third dose, and 2.3% the fourth dose. Of the total vaccinated patients, 39.38% were administered Sputnik-V, 26.02% Pfizer, 16.43% AstraZeneca, 13.35% Moderna, 4.1% Covaxin, and 0.68% Hayat Vax. Of 292 doses administered, 103 AEs were recorded, 79.6% within the first 5 days and the rest within the next 5 days. 44.03% presented the AE after the first dose, 32.11% after the second dose and 23.85% after the third dose. Themean duration of symptoms was 7.49 +/- 9.877 days. The most important side effect was pain at the injection site, followed by fever and fatigue. The worsening of Lupus due to the administration of the anticovid vaccine was demonstrated in 9.93% of the cases. Conclusion(s): Mild effects were registered. It is concluded that vaccination against COVID-19 is safe for individuals with SLE.

Covid-19 in Patients Presenting with Malaria-Like Symptoms at the Korle Bu Polyclinic, Accra

Intro: Malaria is one of Ghana's most frequent illnesses and the most common cause of febrile sickness. Most infectious diseases including COVID-19 and arboviral infections mimic malaria due to the overlapping of non-specific symptoms they both share.This study investigated COVID-19 in patients presenting with malaria-like symptoms at the Korle Bu Polyclinic, Accra. Method(s): This study enrolled 300 patients presenting with malaria-like symptoms aged <= 18. After consent was obtained from study patients, two to three millilitres of whole blood, nasopharyngeal and oropharyngeal swab samples was collected for screening of Plasmodium falciparum using malaria rapid diagnostic test, microscopy and nested PCR and SARS-CoV-2 using SARSCoV-2 antigen test and Real-time PCR respectively. The whole blood sample was also used for COVID-19 antibody test and full blood count using hematological analyser. Finding(s): The detection of SARS-CoV-2 by COVID-19 Rapid Antigen Test and Real-time PCR were 60/300 (20%) and 26/300 (8.7%) respectively. Delta variant was reported in most SARS-CoV-2 positives with CT values below 30. The prevalence of malaria by microscopy, RDT and nested PCR were 7/300 (2.3%), 7/300 (2.3%) and 8/300 (2.7%) respectively. The most common symptom experienced by the study patients at the polyclinic was headache (95%;57/60). Comorbidities reported were hypertension, diabetes, Asthma, hypertension and diabetes. Most of the study patients had been previously exposure to SARS CoV-2 (113/300) and 66.7% (34/51) of AstraZeneca vaccinated patients had no antibody. Conclusion(s): Due to the synergy of symptoms, screening for COVID-19 in patients presenting with malaria-like symptoms is vital for immediate diagnosis and treatment.Copyright © 2023

Sars-Cov-2 Vaccination Coverage in a Mexican Population with Rheumatic Disease

Objectives: Latest recommendation on SARS-CoV-2 vaccination in patients with systemic rheumatic diseases (SRD) by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) is 3 doses while the Centers for Diseases Control and Prevention (CDC) recommends 5 doses. Method(s): We performed a cross-sectional study from April to November 2022 about SARS-CoV-2 vaccination in an outpatient rheumatology clinic in northeast Mexico. Consecutive SRD patients with a history of COVID-19 vaccination were invited to participate. Patients without SRD were excluded. Eligible participants completed a survey that included demographic data (age, sex, rheumatic disease diagnosis) and SARS-CoV-2 vaccination history (number of doses, and type of vaccine). Result(s): We recruited 252 patients.Vaccine types administered were: BNT162b2 (Pfizer-BioNTech) 55 (23.11%);ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) 130 (54.62%);Ad5-nCoV (CanSinoBIO) 31 (13.03%);Coronavac (Sinovac) 9 (3.78%);mRNA-1273 (Moderna)13 (5.46%). (See Table 1 and Table 2) Conclusion(s): Two thirds of our patients met SARS-CoV-2 vaccination recommendations by ACR and EULAR and 5.95% met CDC criteria. Population without any dose represents 6.74%. SARS-CoV-2 infection in vaccinated patients with SRD is associated with a better outcome compared with unvaccinated. Efforts to increase vaccination coverage need to be done.

SARS-CoV-2 Alpha Variant Infection of a Patient Immunized by Inactive Sinovac (CoronaVac) Vaccine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in December 2019, and shortly after pandemic has been declared by the World Health Organization (WHO) due to its unstoppable global spread. Considerable amount of effort has beenput around the World in order to develop a safe and effective vaccine against SARS-CoV-2. Inactivated and RNA vaccines have already passed phase three studies showing sufficient efficacy and safety, respectively. Nowadays, there is a noticeable dominance of SARS-CoV-2 variants with various mutations over the wild type SARS-CoV-2. However, there is no report showing the efficacy of these vaccines on these variants. This case study describes a thirty-eight-year-old male reported to be infected with SARS-CoV-2 alpha variant following two doses of inactive CoronaVac administration with a protective level of SARS-CoV-2 specific antibodies. The variant analysis of the virus reported to be positive for N501Y mutation.This is the first case in the literature demonstrating that inactive SARS-CoV-2 vaccine might have a lower efficacy on alpha variant.Copyright © 2022 Cenk Serhan Ozverel et al., published by Sciendo.

Comparison between COVID-19 and monkeypox vaccine uptake in a diverse London HIV cohort

Background: The COVID-19 pandemic caused millions of deaths, its impact lessened with effective vaccines and treatments. The subsequent monkeypox outbreak posed another global threat, disproportionately affecting men who have sex with men (MSM), with concerns around increasing community stigma. Vaccinating at risk groups is vital in minimising COVID-19 and monkeypox transmissions and adverse sequalae. Our HIV clinic serves a diverse population in a deprived area with a large immigrant population and high level of co-morbidities, associated with poorer outcomes. We explored factors associated with COVID-19 and monkeypox vaccine uptake. Method(s): We reviewed COVID-19 vaccine first, second and third/booster uptake and first smallpox vaccine among MSMs attending our HIV clinic. Monkeypox vaccination is a two-dose course. Initial limited vaccine availability meant first monkeypox vaccine was prioritised for all eligible patients;we therefore analysed first monkeypox vaccination uptake. 186 MSM PLWH were identified. 164 were included in our analysis;22 were excluded due to insufficient vaccination information. Data was recorded contemporaneously in patients' records. COVID-19 vaccine uptake was verified using NHS Summary Care Record and London Care Record. Data on age and ethnicity was collected. Result(s): Demographics: Age: mean 42.9 years, 49% <=40 years, 51% >40 years Ethnicity: 55% White, 26% Black, 5% Asian, 2% mixed, 7% other, 4% not stated COVID-19 vaccination uptake reached statistical significance between age groups: <=40y 53%, >40y 80% (p = 0.001) and ethnicities: White 73%, Black 50%, Asian 67% (p = 0.026). Monkeypox vaccination uptake did not reach significance: <40y 26%, >40y 29%;ethnicity: White 31%, Black 24%, Asian 33%. Additionally, COVID-19 vaccinated patients were not statistically significantly more likely to accept monkeypox vaccination. Conclusion(s): Monkeypox vaccination uptake was similar across ages and ethnicities. However, monkeypox vaccination uptake was considerably lower than COVID-19 vaccination. Further work is needed to identify and engage at risk groups and address obstacles affecting monkeypox vaccination in marginalised communities. Lessons from COVID vaccination campaigns should be employed to reach unvaccinated high-risk MSMs. (Table Presented).

Structure of Adverse Events Following Immunisation against Coronavirus Infection (COVID-19) in the Kyrgyz Republic.

There is considerable interest worldwide in developing safe and effective vaccines against COVID-19. Pharmacovigilance of adverse events following immunisation (AEFIs) is a key to making informed decisions regarding the global COVID-19 vaccination campaign. In the Kyrgyz Republic, there have been developed a national immunisation information system (IIS) for automated recording of vaccines, vaccinated persons, and AEFIs and a mobile application for AEFI reporting, called Den Sooluk. The aim of the study was to analyse the pattern of AEFIs against COVID-19 in the Kyrgyz Republic. Material(s) and Method(s): the study analysed the spontaneous safety reports submitted to the national IIS database through the Den Sooluk mobile application from 29.03.2021 to 25.09.2022. Result(s): according to the data available by 25.09.2022, the total number of vaccinated people in the country amounted to 2,940,082. At the time, the IIS database included 2111 AEFIs: 1 fatal (and coincidental), 3 severe and 2108 minor ones. AEFIs were more frequent in the young and middle-aged population (81.5%), than in the elderly (18.5%). The following AEFIs were reported: injection site pain (21.25%), fatigue (20.7%), headache (19.8%), body temperature above 38 C (10.10%), miscellaneous symptoms (5.12%), chills (4.41%), dizziness (4.32%), sore throat (3.36%), myalgia (2.9%), and nausea (2.2%). Conclusion(s): all COVID-19 vaccines used in the Kyrgyz Republic can be considered adequately safe. Pharmacovigilance of AEFIs is an integral part of the requirements to ensure the safe use of vaccines, and collecting of spontaneous reports on AEFIs supports adequate functioning of the post-marketing surveillance system. It is essential to provide access to electronic information platforms to health professionals and patients in order to ensure vaccination transparency and coordination and enable quick and safe reporting of AEFIs associated with the use of COVID-19 vaccines.Copyright © NEICON ISP LLC. All rights reserved.

Adverse Events Following Oxford-Astrazeneca's COVID-19 Vaccine among Health Care Workers in a Tertiary Care Teaching Hospital: A Prospective Observational Study

Background: The ubiquitous elixir for mortality and morbidity inflicted by severe acute respiratory syndrome virus (SARS-CoV-2) has been a vaccine. These vaccines were approved for emergency use authorization by health authorities based on limited data from clinical trials. Hence, there was a need for active surveillance of vaccinees to monitor for safety. Objective(s): This study reports adverse events following immunization with Oxford-AstraZeneca's COVID-19 vaccine (COVISHIELD). Material(s) and Method(s): The present study is an observational follow- up study to assess any adverse event occurrence following immunization (AEFI) within 7 days of vaccination among all eligible participants who were vaccinated. A structured safety surveillance questionnaire was administered consecutively to 714 participants. Vaccinees were observed for thirty minutes and followed telephonically for adverse events. Result(s): The overall incidence of any AEFI within 7 days was found to be 136/1000 vaccinations for the first dose. Out of total, 97 recipients reported with adverse events, 76.3% had AEFI within 24 h with fever as the most common symptom reported. The incidence of AEFI's was found to be associated with gender (P<0.02), age group (P<0.05) and occupation (P<0.05). No cases of hospitalization, disability or death were reported. Conclusion(s): Most of the adverse events were short-lived and observed in the first 24 h of vaccination. Incidence decreased in subsequent days and as no significant life-threatening adverse event was observed, this study might help reduce hesitancy for vaccination among the population and thus help reduce transmission of this highly contagious disease.

An Audit of Clinico-demographic Profile of Covid-19 Deaths in a Tertiary Care Hospital

Background: Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus with more than 6.5 million deaths worldwide. Objective(s): The aim of this study was to analyze the clinical and demographic profile of covid-19 deaths in Government SMHS Hospital, an associated hospital of Government Medical College, Srinagar. Material(s) and Method(s): A retrospective audit of hospital record of Covid-19 patients who expired over a period of 30 months (April 2020 to October 2022) was done to study their clinical and demographic profile. Detailed history, investigations and co-morbidities were studied to assess their impact on overall mortality. Result(s): Out of a total of 5300 admissions, 3339 (63%) were males and 1961 (37%) were females. Total Covid-19 deaths were 821 (15.5%), of which 15.03% (502/3339) were males and 16.26% (319/ 1961) were females. Mortality rate in severe Covid not-critically-ill was 12.3% while it was 42.4% in critically-ill Covid-19 patients. Majority patients belonged to 60-74 years age-group. Hypertension followed by Diabetes Mellitus were the most common co-morbidities in expired patients. Out of 119 patients managed on Non-Invasive ventilation, 21 (17.6%) died while out of 102 patients managed on Invasive Ventilation, 74 (72.54%) died. Only 24 (5.9%) out of expired 403 patients during 2nd wave of Covid were fully vaccinated. Conclusion(s): The overall in-hospital mortality of Covid-19 patients was 15.5%. Advanced age was a significant predictor of mortality. Vaccinated patients had a significantly lower mortality.

LIMITED INDUCTION OF LUNG-RESIDENT MEMORY T CELLS BY SARS-CoV-2 mRNA VACCINATION

Background: Resident memory T cells (TRM) present at the respiratory tract may be essential to enhance early SARS-CoV-2 viral clearance, thus limiting viral infection and disease. While long-term antigen-specific TRM are detectable beyond 11 months in the lung of convalescent COVID-19 patients after mild and severe infection, it is unknown if mRNA vaccination encoding for the SARS-CoV-2 S-protein can induce this frontline protection. Method(s): We obtained cross-sectional paired blood and lung biopsy samples from patients (n=30) undergoing lung resection for various reasons and assigned them to one of four groups: I.) uninfected unvaccinated individuals (n=5), II.) unvaccinated long-term SARS-CoV-2 convalescent individuals (between 6.0-10.5 months post-infection;n=9), III.) uninfected and long-term vaccinated individuals (between 6.0-7.7 months after the second or third dose;n=10), and IV.) uninfected and short-term vaccinated individuals (between 1.3-1.8 months after the third or fourth dose;n=6). We determined the presence of SARS-CoV-2-specific CD4+ and CD8+ T cells in blood and lung samples after exposure of cells to M, N, and S peptide pools, followed by flow cytometry to detect TRM cells expressing interferon (IFN)gamma and/or CD107a, as a degranulation marker. Result(s): We found that the frequency of CD4+ T cells secreting IFNgamma in response to S-peptides was variable but detectable in blood and lung up to 8 months after mRNA vaccination. Moreover, the IFNgamma response of CD4+ T cells in the lung of mRNA-vaccinated patients was similar to the response found in convalescent patients. However, in mRNA-vaccinated patients, lung responses presented less frequently with a TRM phenotype compared to convalescent infected individuals and, strikingly, polyfunctional CD107a+ IFNgamma+ TRM were virtually absent in vaccinated patients. Conclusion(s): mRNA vaccines might induce memory responses within the lung parenchyma in some patients, potentially contributing to the overall disease control. However, the robust and broad TRM response established in convalescent-infected individuals may offer advantages at limiting disease if the virus is not blocked by initial mechanisms of protection, such as neutralization. Our results warrant investigation of mucosal vaccine-induced resident T cell responses in establishing superior site-specific protective immunity.

FEATURES OF POST-VACCINATION HUMORAL IMMUNE RESPONSE IN THE PERSONS WHO UNDERWENT COVID-19 OF VARIOUS SEVERITY.

The studies on humoral immune response in the individuals who have undergone COVID-19 and vaccinated with anti-COVID vaccines allows us to assess the development of "hybrid" immunity, which contributes to understanding the mechanisms of its formation from the effector phase to the step of immunological memory. We assessed the relative and absolute contents of B cell populations and subpopulations, development of humoral immunity in the patients who suffered with COVID-19 of varying severity being thereafter vaccinated with "KoviVak" and "Sputnik V". The study involved volunteers (age 47.3+/-14.5 years) who beared COVID-19 asymptomatically (n = 32), at moderate severity (n = 21), or had severe form of the disease (n = 12), then being vaccinated with "KoviVak" and "Sputnik V" 6-9 months after their recovery. The groups of vaccinated persons consisted of those who beared severe disease being vaccinated with "KoviVak" (n = 6) or "Sputnik V" (n = 6);moderate cases, vaccinated with "KoviVak" (n = 10) and "Sputnik V" (n = 11);asymptomatic cases vaccinated with "KoviVak" (n = 10) and "Sputnik V" (n = 22). We have determined relative and absolute numbers of B lymphocytes (CD45+CD19+), B1 lymphocytes (CD45+CD5+CD19-CD27-), B2 lymphocytes (CD45+CD19+CD5-CD27-), total population of memory B cells (CD45+CD19+CD5-CD27+), non-switched (CD45+CD19+IgD+CD27+), and switched (CD45+CD19+IgD-CD27+) memory B cells;mature naive B lymphocytes (CD45+CD19+CD27-IgD+), plasmoblasts (CD45+CD19+ CD38+++IgD-CD27+), as well as presence of IgG to S(RBD)-SARS-CoV-2 protein. We have found that the humoral immunity among survivors of COVID-19 of varying severity is expressed for up to nine months. The largest number of volunteers who raised antibodies to SARS-CoV-2 S-protein was registered in the group of seriously ill patients. As soon as 1 month after "Sputnik V" vaccination and until the end of the observation, all the examined subjects in this group became seropositive. 4-5 months after injection of this vaccine, specific immunoglobulins were present in all patients who had asymptomatic or average-severity infection. All volunteers who received "KoviVak" had antibodies to the COVID-19 viral S protein from the beginning to the end of the study. Vaccination, especially with "KoviVak", contributed to the highest increase, both in relative and absolute numbers of memory B lymphocytes in asymptomatic patients. Less pronounced changes in the content of B lymphocytes in COVID-19 patients who had severe and moderate clinical course may be associated with higher levels of these cells prior to injection of the vaccines. A positive correlation was found between the number of memory B cells and presence of immunoglobulins to the S protein SARS-CoV-2 in all examined patients.Copyright © 2023 Russian Association of Allergologists and Clinical Immunologists, St. Petersburg Regional Branch (SPb RAACI). All rights reserved.

DNase analysed by a novel competitive assay in patients with complications after ChAdOx1 nCoV-19 vaccination and in normal unvaccinated blood donors

Increased levels of neutrophil extracellular traps (NETs) have been detected in individuals with vaccine complications after the ChAdOx1 nCov vaccine with a correlation between the severity of vaccine side effects and the level of NETosis. DNases may disrupt NETs by degrading their content of DNA, and a balance has been reported between NETs and DNases. Because of this and since the inflammatory marker NETs may be used as a confirmatory test in diagnosing VITT, it is of interest to monitor levels of DNase in patients with increased NETs levels. The current novel rapid DNase ELISA was tested in blood samples of patients with known increased levels of NETs with or without VITT after ChAdOx1 nCoV-19 vaccination. DNase levels in VITT patients were significantly increased compared with normal unvaccinated blood donors and compared with patients with post-vaccination symptoms but not VITT. However, since EDTA was found to inhibit DNase, serum and not EDTA-plasma samples should be applied for DNase testing. The novel DNase assay may serve as a supplementary test to the NETs test when analysing samples from patients with suspected increased NETs levels.Copyright © 2023 The Scandinavian Foundation for Immunology.

SARS-CoV-2 antibody avidity responses in natural infection and vaccination

Background: In ongoing SARS CoV-2 pandemic, understanding antibody responses have played a key role in measuring extent of exposure, protection from reinfection, vaccine efficacy and serodiagnosis. Antibody avidity is total binding strength of immunoglobulin G (IgG) toward its target epitope. High antibody avidity has been correlated with effective neutralization of the SARSCoV-2 virus. However, the data on avidity responses against COVID-19 infection and vaccination are limited. Objective(s): To understand the avidity responses among sera of naturally infected, recovered COVID-19 patients;naive Covaxin, Covishield vaccinees and breakthrough infections. Material(s) and Method(s): In this study, we utilized an in-house developed SARS-CoV-2 anti-spike receptor binding domain (SRBD) IgG ELISA to optimize the avidity assay. A panel of anti-SARS-CoV- 2 SRBD IgG positive serum samples were treated with known concentration of a chaotropic agent (urea) for disruption of the noncovalent interactions of the antigen-antibody complex. This disruption causes low avidity antibodies to dissociate which gives the percentage of high avidity antibodies present in a serum sample. Additionally, the optimized assay was used to understand the avidity responses among sera belonging to individuals naturally infected and recovered after COVID-19, naive Covaxin and Covishield vaccinees;followed by breakthrough infections. Result(s) and Conclusion(s): The anti-SRBD avidity progressively elevated over a period of twelve months. Moreover, overall antibody avidity responses were similar in the case of natural infection and naive two doses of Covaxin and Covishield vaccinated individuals. However, avidity responses were high among individuals with a breakthrough infection as compared to naive vaccinees.

Two years of the COVID-19 pandemic in the population of Czech patients with inflammatory bowel disease treated with biological therapy*experience of the tertiary IBD center.

Background: Inflammatory bowel disease (IBD) may be associated with a more severe course of infections and a different response to vaccination, especially in complicated IBD course and in association with immune-modifying IBD treatment. The aim of this study was to describe COVID-19 pandemic during years 2020 2022 in IBD patients with long-Term biological therapy. Method(s): A retrospective analysis of SARS-CoV-2 infection incidence in the population of 1,177 IBD (Crohn s disease or ulcerative colitis) patients with long-Term biological therapy (IBD cohort) was performed. The incidence rate, crude incidence rate and standardized incidence ratio of COVID-19 in the IBD cohort, the odds ratio of infection depending on the type of biologic therapy administered, the dynamics of COVID-19 incidence depending on the predominant SARS-CoV-2 variant in the population and the current vaccination coverage of the IBD cohort were calculated. Result(s): From January 2020 to April 2022, 548 confirmed cases of COVID-19 (46.6%) were reported in the IBD cohort, with 39% share of PCR positivity in vaccinated individuals and with 95% occurrence of infection in unvaccinated part of the IBD cohort. Standardized incidence rate ratio of COVID-19 was 27% higher in the IBD cohort compared to the general Czech population. The dynamics of the development of the number of positive cases of COVID-19 in the IBD cohort was identical to the situation in the entire country. A higher odds ratio of the chances of infection was demonstrated in patients treated with tumor necrosis factor inhibitors, but not in patients treated with anti-integrins or monoclonal antibodies against interleukins. In the IBD cohort, 85.2% of patients were properly vaccinated, which was significantly more than the vaccination rate of the entire Czech population. Discussion and conclusion: During the two pandemic years, the incidence of COVID-19 in patients with severe IBD and long-Term biological treatment was higher compared to the general Czech population, despite the favorable vaccination coverage of this high-risk patients group. A higher risk was associated with tumor necrosis factor inhibitor therapy.Copyright © 2023 Galen s.r.o.. All rights reserved.