A cross-sectional study on the seroprevalence of the SARS-CoV-2 IgG antibody in patients with cancer from central Kerala

Background: Patients with cancer are vulnerable to coronavirus disease 2019 (COVID-19). Given the rising number of COVID-19 cases and relaxation of stringent COVID-19 protocols, assessment of the level of protective immunity to COVID-19 in patients with cancer has assumed importance. Objective(s): Our primary objective was to evaluate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in patients with cancer. Material(s) and Method(s): We conducted a cross-sectional study on 100 patients with solid tumors attending our Oncology Department at the Believers Church Medical College, Kerala, India, between December 2020 and June 2021. Seroprevalence was assessed using the VITROS Anti-SARS-CoV-2 IgG test (Ortho-Clinical Diagnostics, Rochester, NY, USA). Additionally, we assessed the factors associated with seropositivity and collected data regarding the general experience of patients with cancer during the pandemic. Result(s): The median age of the participants was 62 years (IQR, 53-69.8);52 (52%) were males. The seroprevalence of the SARS-CoV-2 IgG antibodies was 11% (95% CI, 4.8-17.1). Age < 50 years was the only factor that was significantly associated with a higher rate of COVID-19 antibodies (77% vs 8.9% in patients >= 50 years;P = 0.007), and sex, smoking, and the use of alcohol did not show any association. The majority (77/100, 77%) of the patients were worried about contracting COVID-19 infection;some even deferred cancer-directed treatment because of the fear of visiting health care settings. Conclusion(s): Low seroprevalence of SARS-CoV-2 IgG antibodies in unvaccinated patients with cancer is a matter of concern as it indicates that many of these patients are still vulnerable to infection. There is an urgent need to continue implementing strict safety measures in oncology centers and to encourage widespread COVID-19 vaccination to prevent the uncontrolled spread of COVID-19 among patients with cancer. (Funded by the institution, Believers Church Medical College, Kerala).Copyright © 2023 Neurology India, Neurological Society of India Published by Wolters Kluwer - Medknow.

Risk factors for worsening of somatic symptom burden in a prospective cohort during the COVID-19 pandemic

Aims: Little is known about risk factors for both Long COVID and somatic symptoms that develop in individuals without a history of COVID-19 in response to the pandemic. There is reason to assume an interplay between pathophysiological mechanisms and psychosocial factors in the etiology of symptom persistence. This study investigates specific risk factors for somatic symptom deterioration in a cohort of German adults with and without prior SARS-CoV-2 infection. Method(s): German healthcare professionals underwent SARS-CoV-2 IgG antibody testing and completed self-rating questionnaires at baseline and 21 months later between April 2020 and February 2022. Differences in variables between the time points were analyzed and a regression analysis was performed to predict somatic symptom deterioration at follow-up. Result(s): Seven hundred fifty-one adults completed both assessments. Until follow-up, n = 58 had contracted SARS-CoV-2 confirmed by serology. Between baseline and follow-up, signs of mental and physical strain increased significantly in the sample. Symptom expectations associated with COVID-19 and a self-reported history of COVID-19, but not serologically confirmed SARS-CoV-2 infection, significantly predicted somatic symptom deterioration at follow-up. A further predictor was baseline psychological symptom burden. Conclusion(s): This study supports a disease-overarching biopsychosocial model for the development of burdensome somatic symptoms during the COVID-19 pandemic and supports research findings that symptom burden may be more related to the psychosocial effects of the pandemic than to infection itself. Future studies on Long COVID should include SARS-CoV-2 negative control groups and consider symptom burden prior to infection in order to avoid an overestimation of prevalence rates.Copyright © 2023

Monitoring SARS CoV-2 antibodies positivity in healthcare workers after inactivated CoronaVac vaccine

Introduction In this study, we aimed to monitor anti-spike and anti-nucleocapsid antibodies positivity in healthcare workers (HCWs) vaccinated with two doses of inactivated CoronaVac (Sinovac, China) vaccine. Methods Overall, 242 volunteer HCWs were included. Of the participants, 193 were HCWs without history of prior documented COVID-19 (Group 1), while 49 had history of prior documented COVID-19 before vaccination (Group 2). The participants were followed up for SARS-CoV-2 antibodies positivity at four different blood sampling time points (immediately before the second vaccine dose and at the 1st, 3rd months and 141-150 days after the second dose). We investigated the serum IgG class antibodies against SARS-CoV-2 RBD region and IgG class antibodies against SARS-CoV-2 nucleocapsid antigen by chemiluminescent microparticle immunoassay (CMIA) method using commercial kits. Results We found positive serum anti-RBD IgG antibody in 76.4% of the participants (71% in Group 1;98% in Group 2) 28 days after the first dose. When the antibody levels of the groups were compared at the four blood sampling time points, Group 2 anti-RBD IgG levels were found to be significantly higher than those in Group 1 at all follow-up time points. Although anti-RBD IgG positivity persisted in 95.6% of all participants in the last blood sampling time point, a significant decrease was observed in antibody levels compared to the previous blood sampling time point. Anti-nucleocapsid IgG antibody was positive in 12 (6.2%) of participants in Group 1 and 32 (65.3%) in Group 2 at day 28 after the first dose. At the fourth blood sampling time point, anti-nucleocapsid antibodies were found to be positive in a total of 20 (9.7%) subjects, 10 (6.1%) in Group 1 and 10 (23.8%) in Group 2. Conclusions In this study, it was determined that serum antibody levels decreased in both groups after the third month after the second dose in HCWs vaccinated with CoronaVac vaccine.Copyright © GERMS 2022.

Cellular and humoral immune responses after SARS-CoV-2 vaccination in pediatric kidney recipients

Objective: Humoral and cellular immune responses to SARS-CoV-2 vaccination are reduced in adult kidney recipients. After pediatric kidney transplantation there are only few data available - mostly limited to monitoring of SARS-CoV-2 antibodies. Method(s): Cellular and humoral immune responses have been monitored before and after SARS-CoV-2 vaccination in pediatric kidney recipients. After in vitro stimulation with SARS-CoV-2 antigen (spike glycoprotein) virus-specific CD4 and CD8 T cells (SARS-CoV-2-Tvis) have been identified by cytokine flow cytometry. SARS-CoV-2 IgG was measured by CMIA. Result(s): Immune response after SARS-CoV-2 vaccination was analyzed in a total of 30 pediatric kidney recipients (age at 1st vaccine dose 5.2 - 17.8 years, median 14.8 years;43% male;30/30 2 vaccine doses;23/30 3 vaccine doses). At time of vaccination 22 patients (73%) received a tacrolimus (Tac)-based immunosuppression combined with mycophenolate mofetil (MMF;n = 15) or everolimus (n = 6) or neither of them (n = 1);3 patients were exposed to cyclosporine A and 5 patients to a calcineurin inhibitor (CNI)- free immunosuppression. MMF was used in 18/30 patients. After 1st dose of mRNA vaccine SARS-CoV-2 antibodies were detectable in 50% of pediatric kidney recipients, after 2nd dose in 78% and after 3rd dose in 88%. After the 2nd vaccine dose absence of humoral immune response (< 33.8 BAU/ml) was only found in case of MMF use (predominately combined with Tac). Peak IgG values (> 2,080 BAU/ml) were only detected in MMF-free regimens (6/7). Cellmediated response partially differed from humoral response, e. g., in some patients SARS-CoV2-Tvis were found despite lack of virus-specific antibodies. After 1st vaccine dose SARS-CoV-2-Tvis were detectable in 50% of pediatric kidney recipients, after 2nd dose in 92%. After 2nd vaccine dose absence or very low levels of SARS-CoV-2-Tvis (< 0.3 cells/mul) were only found in Tac-based immunosuppressive regimens, whereas higher levels (> 1.3 cells/mul) were exclusively detected in patients with MMFfree medication. Conclusion(s): After pediatric kidney transplantation humoral and cellular immune responses to SARS-CoV-2 vaccination were suboptimal, but more pronounced than in adult kidney recipients. Use of Tac and MMF was associated with impaired immune response to vaccination. SARS-CoV-2-specific humoral response corresponded only partially to cell-mediated response. Additional monitoring of SARS-CoV- 2-Tvis might be recommendable to improve assessment of the individual vaccine response and thereby to personalize the decision on the necessity of further vaccine doses.

The efficiency of COVID-19 vaccines among taiwanese patients with varied comorbidities

Background/Aims: The global pandemic of COVID-19 has caused tremendous loss of human life since 2019. Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control the pandemic. The vaccination efficacy in Taiwanese patients with different comorbidities is elusive and to be explored. Method(s): Uninfected subjects who received 3-doses of mRNA vaccines (Moderna, BioNTech), non-replicating viral vector-based vaccines (AstraZeneca, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine, MVC) were prospectively enrolled. SARSCoV2- IgG spike antibody level was determined (Abbott [SARS-CoV- 2 IgG II]) within 3 months after the last dose of vaccination. Charlson Comorbidity Index (CCI) was applied to disclose the association of vaccine titer and underlying comorbidities. Result(s): A total of 824 subjects were enrolled in the current study. The mean age was 58.9 years and males accounted for 48.7% of the population. The proportion of CCI with 0-1, 2-3 and>4 was 52.8% (n = 435), 31.3% (n = 258) and 15.9% (n = 131), respectively. The most commonly used vaccination combination was AZ-AZ-Moderna (39.2%), followed by Moderna-Moderna-Moderna (27.8%) and AZAZ- BioNTech (14.7%), respectively. The mean vaccination titer was 3.11 log BAU/mL after a median 48 days of the 3rd dose. Subjects of male gender, lower body mass index, chronic kidney disease, higher CCI, and receiving AZ-AZ based vaccination were likely to have a lower titer of antibody. There was a decreasing trend of antibody titer with the increase of CCT (trend P<0.001). Linear regression analysis revealed that AZ-AZ-based vaccination (beta: 0.341, 95% confidence intervals [CI]: 0.144, 0.21, P<0.001) and higher CCI (beta: - 0.055, CI: - 0.096, - 0.014, P = 0.009) independently correlated with low IgG spike antibody levels. Conclusion(s): Patients with more comorbidities had a poor response to 3 doses of COVID-19 vaccination. Further studies are warranted to clarify the efficacy of booster vaccination in the population. The vaccine titer did not differ between patient with or without chronic liver disease.

Circulation of SARS-CoV-2 Among Asylum Seekers: A Real-Life Experience to Address Health Equity in Piacenza, Italy

Aim of the Study: We aimed to evaluate the virus spreading among a migrant population previously excluded by community surveillance programs. Method(s): We conducted a retrospective study, collecting data about people without SARS-CoV-2-related symptoms who attended the outpatient clinic for undocumented migrants from November 1, 2020, to April 30, 2021. Patients who performed a nasopharyngeal swab and serologic test to evaluate the presence of antibody anti-SARS-CoV-2 were enrolled. Result(s): Overall, 240 people were included in our study. Of them, 15 (6.3%) were female, with a median age of 27.0 years (interquartile range [IQR], 24.3-32.1 years). Thirty-seven patients (15.4%) tested positive for SARS-CoV-2 at the nasopharyngeal swab during the study period. Of these, 16 had positive or low positive results for immunoglobulin G (IgG) and 3 tested positive for both IgG and IgM. Besides, 22 participants (9.2%) resulted positive to serological testing, but negative to polymerase chain reaction testing. The median age of SARS-CoV-2 positive patients (n = 59) was significantly higher than negative (29.6 [IQR, 25.0-35.0] vs 26.8 [IQR, 24.2-31.5], P = 0.022). Among positive patients, the most frequent nationality was Bangladeshi, with 24 people (40.7%, P < 0.001). The highest percentage of positive was found among the same nationality (51.1% of Bangladeshi tested positive). Conclusion(s): Our data underline the significantly higher prevalence of SARS-CoV-2 infection in the undocumented migrant population in respect of the general population of Piacenza province in the same period (15.4% vs 5.9%, P < 0.001). The extension of surveillance programs to the whole population, thus including undocumented people, is crucial to curb the spreading of the virus.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Evaluation of Homologous and Heterologous Vaccine against Sars-Cov-2 in Systemic Lupus Erythematosus Patients: Data from Safer Study

Objectives: To evaluate the immunogenicity of ChAdOx1, Coronavac and BNT162B2 vaccines in SLE patients, including homologous and heterologous immunizations. Method(s): The 'Safety and efficacy on COVID-19 Vaccine in Rheumatic Disease-SAFER study' is a Brazilian multicentric longitudinal phase IV study to evaluate COVID-19 Vaccine in immune-mediated rheumatic diseases (IMRD) in real life, started on May 2021. SLE patients (according to the 2012 SLICC classification criteria), older than 18 years of age were recruited after 2 or 3 doses of vaccine against COVID-19 (ChAdOx1, BNT162b2 and CoronaVac) and were evaluated at baseline and on the 28th day after each dose. Homologous immunization was considered if they received three doses of the same vaccine and heterologous if a different one was applied. IgG antibody against SARS-CoV-2 spike receptor-binding domain were measured by chemiluminescence (SARS-CoV-2-IgG-II Quant assay, Abbott-Laboratories) at baseline and 28 days after the first, 2nd and 3rd doses (Seropositivity IgGSpike>= 7.1BAU/mL). Statistical analysis: ANOVA and pairwise comparisons tests Results: 316 SLE patients were included (255 heterologous and 61 homologous immunization), 89.2% were female and the mean age was 37.6 +/- 11.2 years. The two groups were homogeneous regarding demographical data, disease activity and immunosuppressive treatment. 49.7% used corticosteroids (alpha 5 mg/day in 52.3%), 83.5% antimalarials, 22.8% azathioprine and 20.3% mycophenolate mofetil. 207 patients received the first two doses with CoronaVac, 128 ChadOx-1 and 32 BNT162b2. Regarding the first two doses of the same vaccine, there was no difference in IgG titers over time between CoronaVac or ChadOx-1 (p = 0.313). IgG titers increased in all vaccine groups, with difference only after 2nd dose: 4.96 +/- 1.71BAU/mL CoronaVac vs. 6.00 +/- 1.99BAU/mL ChadOx-1 vs. 7.31 +/- 1.49BAU/mL BNT162b2 (p alpha 0.001). There was no difference in IgG titers over time between homologous or heterologous vaccine schedule (p = 0.872). IgG titers also increased in all groups, with difference only after 2nd dose: 5.49 +/- 1.96BAU/mL heterologous vs. 6.30 +/- 2.10BAU/mL homologous (p = 0.009). Conclusion(s): Induction of immunogenicity occurred in different vaccine regimens in SLE patients. Future research to explore different heterologous schemes in IMRD must be performed.

Impact of Covid-19 and Host Factors on the Humoral Immune Repertoire in Treated Hiv

Background: People with HIV (PWH) on antiretroviral therapy (ART) appear to be at higher risk for worse COVID-19 outcomes, but the underlying mechanisms-including effects of COVID-19 and host factors on the broader humoral immune repertoire-are poorly understood. Method(s): REPRIEVE enrolled a global cohort of ART-treated PWH ages 40-75. COVID+ was defined by positive receptor binding domain IgG or IgA from annual visits 5/2020-2/2021. Antibody isotype, subclass, and Fc receptor Luminex arrays to SARS-CoV-2, CMV, EBV, HSV, HIV, influenza, pneumococcus, and RSV were assessed. Report of COVID diagnosis (collected every 4 months) was defined as mild, moderate, or severe (asymptomatic if no clinical diagnosis but IgG/ IgA+). FDR-corrected regression was used to assess effects of 1) COVID+ on non- SARS-CoV-2 repertoire in full cohort and 2) host factors on non-SARS-CoV-2 and SARS-CoV-2 repertoire in COVID- and COVID+ cohorts, respectively, adjusted for age, sex, region, nadir CD4, and HIV VL at entry. Result(s): Of 2,464 unvaccinated participants, 283 (11%) were COVID+;260 (92%) were asymptomatic. Median age was 53, 35% were women, 50% had nadir CD4 < 200, median current CD4 was 649, and 97% had HIV VL < 400. In the full cohort, COVID+ was associated with higher CMV PP65 IgG3 and FcgammaRIIA (P< 0.05);COVID severity was not associated with the non-SARS-CoV-2 repertoire. Among COVID-, older age, female sex, and lower nadir CD4 were associated with higher EBV and CMV responses;IgG1 levels were higher in women for all non-SARS-CoV-2 antigens assessed (P< 0.05). Among COVID+, higher BMI was associated with amplified SARS-CoV-2 IgG, IgA, IgM, and FcgammaRIIA responses (P< 0.05). Lower nadir CD4 was associated with a SARSCoV- 2 repertoire shift toward IgM and FcgammaRIIB (P< 0.05). Age and sex were not associated with SARS-CoV-2-related repertoire changes in COVID+. Conclusion(s): Our analysis presents a comprehensive view of host factors associated with the humoral immune repertoire among a global cohort of ART-treated PWH. COVID's association with higher CMV responses may suggest increased susceptibility to or a consequence of persistent inflammation after infection. The striking amplification of SARS-CoV-2 responses with higher BMI suggests an excessive inflammatory response. Lower nadir CD4 was related to uncontrolled extra-follicular and inhibitory SARS-CoV-2 responses, which are unlikely to be protective. These findings may suggest mechanisms underlying factors associated with worse COVID-19 outcomes among PWH. (Figure Presented).

IMMUNOGENICITY OF SARS-CoV-2 mRNA VACCINATION IN IDIOPATHIC CD4 LYMPHOPENIA

Background: The rapid development of SARS-CoV-2 mRNA vaccines has been a remarkable success of the COVID-19 pandemic, but vaccine-induced immunity is heterogeneous in immunocompromised populations. We sought to determine the immunogenicity of SARS-CoV-2 mRNA vaccines in a cohort of people with idiopathic CD4 lymphopenia (ICL). Method(s): 25-patients with ICL followed at the National Institutes of Health on a natural history protocol were evaluated between 2020-2022. Blood and serum was collected within 4-12 weeks after their second and/or third SARS-CoV-2 mRNA vaccine dose. Twenty-three matched healthy volunteers (HVs) provided blood samples at similar timepoints post-mRNA vaccination on a separate clinical protocol. Pre-vaccine blood samples were also used when available. Anti-spike and anti-receptor binding domain antibodies were measured. T-cell stimulation assays were performed to quantify SARS-CoV-2 specific T-cell responses. Comparisons were made with Wilcoxon test. Result(s): Twenty-participants with ICL had samples collected after their second mRNA vaccine and 7-individuals after the third dose. Median age at vaccination was 51-years (IQR: 44-62) and 12 were women (48%). Median CD4 T-cell count was 150 cells/muL (IQR: 85-188) at the time of vaccination, and 11-individuals (44%) had a baseline CD4 count <=100 cells/muL. HVs had a median age of 54-years (IQR: 43-60) with 13-women (56.5%). Anti-spike IgG antibody levels were significantly greater in HVs than those with ICL after 2-doses. Lower SARS-CoV-2 IgG antibody production was primarily observed in those with baseline CD4 T-cells <=100 cells/mul (Figure-1A). The decreased production in ICL remained after a third vaccine dose (Figure-1B). There was a significant correlation between anti-spike IgG and baseline CD4 count. Spike-specific CD4 T-cell responses in volunteers compared to those with ICL demonstrated similar levels of activation induced markers (CD154+CD69+) and cytokine production (IFNgamma+, TNFalpha+, IL2+) after two or three mRNA vaccine doses. Quantitatively the smallest responses were observed in those with lower baseline CD4 T-cells (Figure 1C-D). Minimal SARS-CoV-2 CD8 T-cell responses were detected in both groups. Conclusion(s): Patients with ICL and baseline CD4 T-cells >100 mount similar humoral and cellular immune responses to SARS-CoV-2 vaccination as healthy volunteers. Those with baseline CD4 T-cells <=100 have impaired vaccine- induced immunity and should be prioritized to additional boosters and continue other risk mitigation strategies. (Figure Presented).

12-MONTH HUMORAL RESPONSE AFTER mRNA COVID-19 VACCINATION IN PEOPLE LIVING WITH HIV

Background: We compared the 12-month post primary vaccination humoral immune response to mRNA COVID-19 vaccines in PLHIV and controls. Method(s): PLHIV and HIV-negative healthy controls included in the French national multi-center prospective COVID 19 vaccine cohort study ANRS0001S COV-POPART were analyzed. Percentage (95% CI) of responders (positive anti- Spike SARS-CoV-2 IgG antibodies) and geometric means titers (95% CI) of anti-Spike SARS-CoV-2 IgG antibodies (BAU/mL) were assessed at 1 month and 6 months (M) after the 2nd dose of the primary vaccination and at 12 months in those who received a booster dose. Specific neutralizing antibodies (nAbs) (in vitro neutralization assay against original, Delta and Omicron BA.1 strains) were estimated in a subset of participants. Serological tests (ELISA Euroimmun) and seroneutralization were performed centrally. Result(s): Overall, 858 PLHIV and 1156 controls were included. PLHIV were older than controls: 55.2 years, (49.6-60.6) vs 46.6 years (36.3-56.6) and more frequently male (75.1% vs 48.9%). Among PLHIV at inclusion, 97.3% were under antiretroviral therapy, 95.6% had an undetectable viral load and 71.8% had CD4 counts above 500 cells/mm3. Participants had namely received BNT162b2 as the primary vaccination (93% in PLWHIV vs 84% in controls) and 53.1% had received a booster dose (57.2% in PLHIV (median time after the 2nd dose: 6.1 M [5.9-6.7]) and 50.1% in controls (median time 6.0 M [5.5-6.2])). Percentage of responders after the 2nd dose was lower in PLHIV than controls ((98.7% [97.7;99.3] vs 99.9% [99.5;99.9], p=0.0001)). PLHIV had significantly lower levels of anti-Spike antibodies at 1 M ((1188 [650;2067] vs 1506 [950;2507] BAU/mL, p< 0.0001)) and 6 M (149 [95;235] vs 194 [124;314] BAU/mL, p=< 0.0001) but similar levels at 12 M (520 [269;1198] vs 427 [259;1087] BAU/mL, p=0.3387) (Figure A). PLHIV had significantly lower nAbs against original, Delta and Omicron BA.1 strains at 1, 6 and 12 M after primary vaccination compared to controls. The booster dose significantly increased the titers of nAbs against original and Delta strains and, to a lower extent, against Omicron (Figure B). Conclusion(s): PLHIV had high response rates to mRNA COVID-19 vaccines but lower titers of antibodies and nAbs at 1 and 6 M after primary vaccination than controls. One mRNA booster dose increased SARS-CoV-2 IgG antibodies titers to similar levels to controls but neutralizing activity especially against Omicron remained lower. (Figure Presented).

Plasma Antibody and N Antigen Status Predict Outcomes in Outpatients with Covid-19

Background: Reliable biomarkers of COVID-19 severity and outcomes are critically needed for clinical and research applications. We evaluated associations between anti-Spike IgG and SARS-COV-2 nucleocapsid antigen (N Ag) in plasma with clinical outcomes in outpatients with COVID-19. Method(s): We used data from 229 non-hospitalized, US-based adults with COVID-19 who enrolled between January and July 2021 into the placebo arm of the ACTIV-2/A5401 platform trial within 10 days of symptom onset. Pretreatment (day 0) plasma was analyzed by the quantitative Simoa SARS-CoV-2 IgG antibody (anti-Spike) assay (lower limit of quantification [LLoQ] 0.77ug/ mL), and the quantitative Simoa SARS-CoV-2 N Protein Advantage (Quanterix) measuring N Ag (LLoQ 3pg/mL). In addition to analyses for < LLoQ vs >=LLoQ anti-Spike and N Ag, we categorized participants into five N Ag groups (< 3 pg/ml;3-< 100 pg/ml;100-< 1,000 pg/ml;1,000-< 2,500 pg/ml;>=2,500 pg/ ml). Associations between SARS-CoV-2 anti-Spike and N Ag levels and clinical outcomes (all-cause hospitalization/death through day 28 and time to symptom improvement or resolution for two consecutive days from day 0 status) were estimated using log-binomial and Cox regression models, respectively. Result(s): At day 0, 40% had anti-Spike levels >=LLoQ and 64% of participants had plasma N Ag levels >=LLoQ. Participants with anti-Spike levels < LLoQ compared to those who had quantifiable anti-Spike at day 0, had an increased risk of hospitalization/death (16% vs 2%, RR [95% confidence interval (CI)]: 7.3 [1.8, 30.1]), and a significantly longer time to symptom improvement (median [Q1, Q3] 14 days [8, >27] vs 9 days [4, 16], hazard ratio [HR]: 0.6 [95%: CI: 0.4, 0.8], p< 0.001). Participants with higher N Ag levels at day 0 had an increased risk of hospitalization or death, ranging from 1% for < 3 pg/ml to 70% for >=2500 pg/ml (Figure). Compared to individuals who had N Ag levels < LLoQ at day 0, those in the highest category of N Ag levels (>=2500 pg/mL) experienced a significantly longer time to symptom improvement (median [Q1, Q3]: 25 days [13, >27] vs 10 days [5, 20];HR: 0.4 [95% CI: 0.2, 0.7];p=0.04). Conclusion(s): At study entry, the absence of Spike antibodies and higher levels of plasma SARS-CoV-2 N Ag predicted hospitalizations and death in untreated outpatients with COVID-19. These parameters may serve as informative biomarkers for risk stratification in the evaluation of outpatients with COVID-19. (Figure Presented).

PROLONGED SARS-CoV-2 VIRAL BURDEN IN SIV-SARS-CoV-2 COINFECTED MACAQUES

Background: Individuals living with HIV are at increased risk of morbidity and mortality from COVID-19. Furthermore, SARS-CoV-2 infection in immunocompromised HIV infected individuals poses a risk to prolonged infection and viral shedding and the emergence of new variants of concern (VOCs). Using the SIV macaque model for AIDS, we are investigating the hypothesis that immune dysfunction during HIV infection will prolong SARSCoV- 2 viral infection, promote enhanced COVID-19 disease, and accelerate viral evolution. Here, we report the impact of SIV-CoV-2 co-infection on immune responses and pathogenesis. Method(s): Eight female rhesus macaques (aged 7-15 years, 5.5-9.9kg) were infected with SIVmac251 via low dose intravaginal challenge and then inoculated with 6.5x105 TCID50/mL SARS-CoV-2 (WA-1) at 17-34 weeks post-SIV infection via combined intranasal and intratracheal routes. Blood, bronchoalveolar lavage (BAL), stool, and nasal, oral, and rectal swabs were collected pre-infection through 14 days post-infection (DPI) to measure immune responses and viremia. ELISAs, ELISPOT, qRT-PCR, lung pathology, cytokine multiplex, and virus neutralization assays were performed to measure viral loads, pathogenesis, and immune responses. Result(s): Three days post-SARS-CoV-2 infection, we observed a transient decrease in CD4 counts, but there were no changes in clinical symptoms or plasma SIV viral loads. However, SARS-CoV-2 replication persisted in the upper respiratory tract, but not the lower respiratory tract. In addition, SARS-CoV-2 IgG seroconversion was delayed and antigen-specific T-cell responses were dampened. Notably, viral RNA levels in nasal swabs were significantly higher 7-14 DPI in SIV+ compared to previously published results using the same SARS-CoV-2 challenge virus in SIV- rhesus (PMCID: PMC8462335, PMC8829873). In addition, SIV/CoV-2 co-infected animals exhibited elevated levels of myeloperoxidase (MPO), a marker of neutrophil activation and increased lung inflammation. Conclusion(s): Here we provide evidence for the utility of the rhesus macaque in modeling human HIV-SARS-CoV-2 co-infection. Our results suggest that immunosuppression during SIV infection impairs de novo generation of anti-SARS-CoV-2 immunity, that may contribute to prolonged SARS-CoV-2 viral shedding, increased transmission windows, altered disease pathogenesis, and lower protection against subsequent SARS-CoV-2 exposures. Studies in progress will determine if SARS-CoV-2 viral evolution is accelerated in SIV-infected macaques.

RESPIRATORY DISEASE FACTORS LINK WITH REDUCED SARS-CoV-2 SUSCEPTIBILITY IN PWH

Background: Despite favorable vaccine responses of people with HIV (PWH), susceptibility to SARS-CoV-2 (SCv2) infection and increased risk of COVID-19 in immunocompromised PWH continue to be of concern. Here, we searched the Swiss HIV Cohort Study (SHCS) with>9500 actively enrolled, optimally treated PWH to identify factors associated with SCv2 infection in the pre-and postvaccination area. Method(s): We utilized information on SCv2 events reported to the SHCS in 2020 -2021. To detect asymptomatic infection, we screened pre-pandemic (2019) and pandemic (2020-2021) bio-banked plasma for SCv2 antibodies (Ab). SCv2+ and matched SCv2- PWH were additionally screened for Abs to circulating human coronaviruses (HCoV). Data were compared to HIV negative (HIV-) controls. SCv2 data and >26 behavioral, immunologic and disease-parameters available in the SHCS data base were analyzed by logistic regression, conditional logistic regression, and Bayesian multivariate regression. Result(s): Considering information on the SCv2 status of 6270 SHCS participants, neither HIV-1 viral load nor CD4+ T cell levels were linked with increased SCv2 infection risk. COVID-19-linked hospitalization (87/982) and case fatality rates (8/982) were low, but slightly higher than in the general Swiss population when stratified by age. Compared to HIV-, PWH had lower SCv2 IgG responses (median effect size= -0.48, 95%-Credibility-Interval=[-0.7, -0.28]). Consistent with earlier findings, high HCoV Abs pre-pandemic (2019) were associated with a lower risk of a subsequent SCv2-infection and, in case or infection, with higher Ab responses. Examining behavioral factors unrelated to the HIV-status, people living in single-person households were less at risk of SCv2 infection (aOR= 0.77 [0.66,0.9]). We found a striking, highly significant protective effect of smoking on SCv2 infection risk (aOR= 0.46 [0.38,0.56], p=2.6*10-14) which was strongest in 2020 prior to vaccination and was even comparable to the effect of early vaccination in 2021. This impact of smoking was highly robust, occurred even in previous smokers and was highest for heavy smokers. Conclusion(s): Our unbiased cohort screen identified two controversially discussed factors, smoking and cross-protection by HCoV responses to be linked with reduced susceptibility to SCv2, validating their effect for the general population. Overall weaker SCv2 Ab responses in PWH are of concern and need to be monitored to ensure infection- and vaccine-mediated protection from severe disease.

Evaluation of Antibody Response and Side Effects Related to the Number of Inactive and mRNA Vaccine Doses Against COVID-19 in Healthcare Workers

Introduction: Studies are showing that a high antibody response increases the protection against variants in the fight against the COVID-19 pandemic. In this study, we aimed to investigate the relationship between antibody response and side effects based on the number of doses administered to healthcare workers who were vaccinated against COVID-19. Material(s) and Method(s): Healthcare workers, who were vaccinated with two doses of BNT162b2 (Group 1), a single dose of BNT162b2 following two doses of CoronaVac (Group 2), or two doses of BNT162b2 following two doses of CoronaVac (Group 3), were randomly assigned to this study. Serum samples were taken from the participants 30 +/- 2 days after the last vaccination date, and the SARSCoV- 2 anti-spike S1 RBD IgG test was administered to these samples. A questionnaire was conducted detailing the demographics of the patients as well as their post-vaccination complaints. The results were analyzed statistically. Analysis results with a p-value of <0.05 were considered significant. Result(s): A total of 179 healthcare professionals with a mean age of 41.7 +/- 10.6 years were included in our study. Of the studied samples, 95.5% (n= 171) were interpreted as anti-spike S1 RBD IgG seropositive. Positivity rates and mean antibody levels were 93.2%, 95.9%, 97.8%, and 107.4 +/- 117.1, 152.7 +/- 108.5, 201.4 +/- 114.9 (AU/mL) for Group 1, Group 2, and Group 3, respectively (p< 0.05). In general, no significant differences in antibody response were seen based on gender or age. However, a significant correlation was found between the occurrence of vaccine-related side effects and antibody titer (p< 0.001). The most common side effect was pain in the area where the vaccine was administered, with a rate of 77.4% (n= 48). More vaccine-related side effects were reported in participants under the age of 40 and in female healthcare workers. Conclusion(s): We believe that booster doses are effective for increasing the immune response and thus protecting against COVID-19. More extensive research should be conducted to confirm the link between the occurrence of vaccine-related side effects and antibody titer. Furthermore, studies on the safety of increasing the number of vaccine doses are required.Copyright © 2023 Bilimsel Tip Yayinevi. All rights reserved.

Post-infectious serum neutralizing SARS-CoV- 2 anti-S protein specific IgG antibody response and decay over a 6-month 3-point sequential concentrations measurement after COVID-19 infection in health care workers

Background: Healthcare workers (HCW) were heavily exposed to iterative viral loads during SARS-CoV- 2/ COVID-19 pandemic. Post-infectious serum neutralizing anti-S/ SARS-CoV- 2 IgG antibody concentrations (anti-S sIgG), albeit a controversial biomarker of antiviral immune response efficacy is actually the only available in routine clinical practice. Method(s): Sequential serum anti-S sIgG measurement (chemiluminescence immunoassay;cut-off: >=1AU/mL) at 3 time-points: T0 = 50.3 +/- 15.3 days after symptom onset (dSo), 16.8 +/- 12.0 days after quarantine end (dQe);T1 = 143.1 +/- 43.9 dSo, 109.4 +/- 43.0 dQe;T2 = 241.3 +/- 75.5 dSo, 208.6 +/- 75.6 dQe;disease severity was classified as asymptomatic (IS1), mild/moderate (IS2) and severe/very severe (IS3) levels. We've enrolled 177 out of 193 positive SARS-CoV- 2/ RT-PCR HCW (8.3% initial dropout), 76.2% female/mean age = 39.6 +/- 11.7 years (y), 23.8% male/mean age = 41.1 +/- 13y, between March and May 2020, out of 4200 HCW of a university hospital. Out of these 177, 93.8% worked in COVID-19 high-risk areas, 72.5% were nurses or assistants, 7.8% had asymptomatic infection and 6.7% suffered serious illness demanding inpatient care. Result(s): At T0, 73.5% HCW (144+ve/166) yielded over-cutoff anti-S sIgG (sIgGoc), mean (sIgGm) = 12.5 +/- 9.1 AU/mL, IS1 = 7.3%, IS2 = 84.9% and IS3 = 7.8%;at T1, sIgGoc = 48.2% (80+ve /166), sIgGm = 2.7 +/- 4.9 AU/mL, IS1 = 7.8%, IS2 = 86.2%, IS3 = 6.0%;at T2, sIgGoc = 25.4% (31+ve /122;late drop out:44), sIgGm = 1.3 +/- 2.8 AU/ mL, IS1 = 8.9%, IS2 = 81.3%, IS3 = 9.8%. So, a progressive decrease in mean serum neutralizing anti-S/ SARS-CoV- 2 IgG antibody concentrations was evident during the first six months after disease, in consonance with available data. Under cutoff concentrations were evident 6 weeks after infection in 26.5% of HCW, in 51.8% after 4 months and 74.6% after 6 months, approximately and even in over-cutoff measurements, values approached the threshold of positivity. Conclusion(s): These results suggest that post-infectious natural immunity against SARS-CoV- 2 is tendentially weak and fast waning, reinforcing the need to repeatedly boost recovered HCW. This measure, together with the collective protection measures and the use of adequate personal protective equipment, will maximize the protection for HCW and patients altogether.

Expert Consensus on Rapid SARS-CoV-2 Antigen Testing.

The epidemic of the highly contagious, long lasting and widely popular coronavirus disease 2019 (COVID-19) has imposed a huge burden to the global public health. As one of the key methods for early diagnosis of COVID-19 infection, rapid acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen testing has been gradually applied in China. To address concerns raised by both health care workers and the public, based on the latest research and clinical practices, the Sub-committee of the Clinical Microbiology Laboratory of the Chinese Hospital Association proposed"Expert Consensus on Rapid SARS-CoV-2 Antigen Testing(2022)". The consensus panel is composed of experts from multiple disciplines, including laboratory medicine, clinical medicine, infection control, public health, research and development of in vitro diagnostic products. The consensus describes its principle, technological characteristics, results interpretation and, disposal recommendations, and analyzes the strategies and matters needing attention in different application scenarios. We expect the consensus to help correct understanding and application of rapid SARS-CoV-2 antigen testing in the diagnosis, treatment, prevention, and control of COVID-19.Copyright © 2022, Peking Union Medical College Hospital. All rights reserved.

Evaluation of a new lateral flow assay for the quantitative detection of Anti-SARS- CoV- 2 specific IgG

Background: Antibody testing for COVID-19 may represent an interesting tool to document past SARS-CoV- 2 infections, both in individual patients with suspected COVID-19 symptoms or late-stage complications who had no (conclusive) PCR test. In addition, measuring SARS-CoV- 2 antibodies may offer a prognostic value and convey information on protective immunity in vaccination trials. The objective of the study is the evaluation of a rapid test for the quantitative interpretation of Anti-SARS- CoV- 2 IgG compared with other in-vitro methods. Method(s): The Anti-SARS- CoV- 2 LFA (Lateral Flow Assay) is a rapid test for the quantitative measurement of IgG antibodies to SARS-CoV- 2 in human serum, plasma and whole blood within 20 minutes. The complexes of Anti-SARS- CoV- 2 antibodies from patient's sample and coloured conjugate are retained at the test line by the complete SARS-CoV- 2 Spike Protein. The use of a special scanner system provides the opportunity of quantitative interpretation of the results, by using calibration curve established with "First WHO International Standard for anti-SARS- CoV- 2 immunoglobulin (human)". Result(s): Serum samples were taken from the serum bank at Dr. Fooke Laboratorien GmbH and tested for Anti-SARS- CoV- 2 IgG by the newly developed LFA (Dr. Fooke Laboratorien GmbH). The results were compared with established assay methods like Anti-SARS- CoV- 2 ELISA IgG (Dr. Fooke Laboratorien GmbH and Euroimmun). Good agreements were observed. Sensitivity and specificity between the newly developed LFA and Anti-SARS- CoV- 2 ELISA IgG of Dr. Fooke / Euroimmun were found at 0.95/0.88 and 1.00/0.93, respectively. The calibration curve established with "First WHO International Standard for anti-SARS- CoV- 2 immunoglobulin (human)" shows a reproducibility of > 90%. Conclusion(s): The Anti-SARS- CoV- 2 LFA shows comparable results to the ELISA systems of Dr. Fooke Laboratorien and Euroimmun. By the use of small amounts of serum, plasma or whole blood (10muL) the patients receive a fast and reliable result. A calibration curve, established with "First WHO International Standard for anti-SARS- CoV- 2 immunoglobulin (human)" offers the comparability to quantitative ELISA systems.

Non-contrast cardiac magnetic resonance imaging after SARS-CoV2 infection or vaccination in asymptomatic adolescents: Insights from the EnIGMA study

Background: Myocarditis after SARS-CoV2 infection or vaccination is rare, but seems to be relatively more frequent in young population. Cardiac magnetic resonance (CMR) T2 weighted sequences have the potential to detect subclinical myocarditis. However, there is paucity of data on the potential myocardial involvement after SARS-CoV2 infection or vaccination in asymptomatic adolescents. Purpose(s): To evaluate the presence of subclinical myocardial damage in adolescents who were infected with SARS-CoV2 or vaccinated against SARS-CoV2 using non-contrast CMR imaging. Method(s): Asymptomatic adolescents enrolled in the Early ImaginG Markers of unhealthy lifestyles in Adolescents (EnIGMA) project were scanned using a 3-Tesla CMR scanner between March 2021 and October 2021. CMR scans included CINE imaging and myocardial T2-mapping sequences. SARS-CoV2 IgG antibody testing was performed in capillary blood samples, and date of confirmed SARS-CoV2 infection and/or vaccination if any was collected. Participants were assigned to three different groups according to SARS-CoV2 status: Group 1 (non-infected and nonvaccinated), Group 2 (infected and non-vaccinated), and Group 3 (vaccinated, independently of past infection status). CMR images were analyzed by experienced observers blinded to adolescent's SARS-CoV2 status. ANOVA and multiple regression analysis, together with correlation coefficients, were used to study between-group differences and associations among variables of interest. Result(s): A total of 115 adolescents with a mean age of 16.0 years (standard deviation (SD)=0.4), 54% girls, completed the CMR study and SARSCoV2 data successfully, and were assigned to Group 1 (n=72), Group 2 (n=22), and Group 3 (n=21). Left and right ventricular ejection fraction (LVEF/RVEF) did not significantly differ among groups: Mean LVEF was 62.8% (SD=4.1), 63.0% (SD=3.7) and 60.9% (SD=3.9) [p=0.12] and mean RVEF was 56.5% (SD=4.2), 56.5% (SD=5.5) and 54.5% (SD=5.1) [p=0.23] in Groups 1, 2 and 3, respectively. Similarly, there were no between-group significant differences in myocardial T2 relaxation values: Mean T2 values were 44.1 ms (SD=2.2), 44.1 ms (SD=1.8) and 44.4 ms (SD=1.9) in Groups 1, 2, and 3, respectively (p=0.63) (Figure 1). No differences were found either after adjusting for age and gender. Median time (interquartile range) from date of infection or vaccination to CMR acquisition was 133 (121) days and 28 (38) days in Group 2 and Group 3, respectively. No correlation between time from infection/vaccination to CMR acquisition and T2 values was detected (Figure 2). Conclusion(s): This observational study did not find evidence of subclinical myocardial involvement after SARS-CoV2 infection or vaccination in asymptomatic adolescents, as assessed with T2-mapping magnetic resonance imaging.

Rapid Detection of Sars Cov-2 Infection in Comparision with Rt-Pcr in Tertiary Care Hospital

Objectives: The goal of the present study was to assess the SARS-CoV-2 antigen detection test's performance features and compare them to the real-time reverse transcription polymerase chain reaction (RT-PCR) test, the gold standard test for the diagnosis of COVID-19 cases. Method(s): From October 2020 to May 2021, patients attending the OPD, including those undergoing surgery, at a Tertiary Care Teaching Hospital in Telangana provided 1000 respiratory samples, primarily nasopharyngeal swabs. A skilled technician had collected two nasopharyngeal swabs from each person in a COVID sample collection room while wearing personal protective equipment and following strict infection control procedures. One swab was used for the rapid antigen test given by the standard Q COVID-19 Ag test kit and placed into the extraction buffer tube. Second swab was kept in the viral transport medium and used for AllplexTM 2019-nCoV Assay (Seegene, Korea), which targets envelope gene (E), and RNA dependent RNA polymerase (RdRp) and nucleocapsid (N) genes of SARS CoV-2, was used for SARS-CoV-2 RNA detection according to the manufacturer's instructions. Result(s): Out of 1000 samples tested for COVID-19, 623 (63.7%) were males and 377 (36.3%) were females. Out of 1000 samples, 347 samples were RT-PCR positive and 653 were RT-PCR negative. Out of 347 RT-PCR samples positive, 341 were Rapid antigen test positive samples and six were negative. Overall sensitivity and specificity are 98.27% and 99.85%, respectively. Conclusion(s): The real-time RT-PCR assay's sensitivity and specificity were comparable to those of the rapid assay for SARS-CoV-2 antigen detection. It can be utilized for contact tracing measures to control the COVID-19 pandemic in places such as border crossings, airports, interregional bus and train stations, and mass testing campaigns needing quick findings. This is especially true in areas with a high prevalence of the disease.Copyright © 2023 The Authors. Published by Innovare Academic Sciences Pvt Ltd.