Impact of Glucocorticoid on Immunogenicity among Covid-19 Vaccines in Immune-Mediated Diseases

Objectives: The use of glucocorticoids (GC) has been associated with increased risk of hospitalization for coronavirus infection and reduced immunogenicity of SARS-CoV-2 vaccines in immune-mediated diseases (IMD) patients. However, there is still controversy of which dose of GC is correlated with impaired vaccine response on each of the diverse COVID-19 vaccines available, as well as the possible influence of other concurrent immunosuppressants. This study aimed at evaluating the effect of GC on serological response after two doses of BNT162b2 (Pfizer/BioNTech), CoronaVac (inactivated SARS-CoV-2 Vaccine) and ChadOx1 (AstraZeneca) and after the booster dose in patients with IMD. Method(s): The data were extracted from a multicenter longitudinal observational Brazilian cohort (SAFER: Safety and Efficacy on COVID19 Vaccine in Rheumatic Disease). Patients >18 years of age with IMD were evaluated after 2 doses of the same vaccine against COVID-19 and after a booster vaccine, applied according to Brazilian National Immunization Program. All patients underwent clinical examination and collected blood samples for immunogenicity tests. Serological response was evaluated by Anti-RBD titers (IgG) at baseline and 4 weeks after each vaccine dose. Result(s): Among the 1009 patients evaluated, 301 were using GC (196/401 SLE, 52/199 RA and 27/74 vasculitis). Patients using GC were younger (38.2 vs 40,8 years, p = 0,002), had higherBMI (27,6 vs 26,4 p = 0,008), higher prevalence of kidney disease (3,3% vs 0,5%, p = 0,001) and of thrombosis (11,6% vs 5,9%, p = 0,002) than non-users. Regarding the type of vaccine, most of the GC users received CoronaVac (61.7%), while only 31.9%of non-users received this vaccine (p alpha 0.001). Although there were similar rates of pre-vaccination infections among them, patients with GC tended to have a higher incidence of confirmed COVID-19 infection after the 2nd dose of the vaccine compared to non-users (4.5% vs 2.0% p = 0.054). The antibody titers after the 1st dose of COVID-19 vaccines were similar between groups, but there was a worse response in the GC group after the 2nd dose (p = 0.039). However, this difference was not statistically significant after the 3rd dose (Figure). Conclusion(s): GC use may compromise vaccine-induced immunogenicity after a 2-dose regimen;however, this effect does not remain significant after the booster dose. Multivariate analysis is still pending to assess the potential difference in the impact of GC on the immune response depending on GC dose, type of vaccine and associated drugs.

Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure

The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).Copyright © 2021 Rando et al.

The impact of gender in the COVID-19 pandemic

Data worldwide is pointing towards an increased mortality of men a from COVID-19, while infection rates are equal or higher in women. Immunological differences might play a role in this as well as differences in risk factors and co-morbidities. In addition, differences in exposure, testing, case definitions and access to healthcare might play a role. Differences in symptoms have been reported, as well as potential differences in therapeutic choices. Also, the phenomenon of long COVID with all its psychophysical consequences appears to be more common in women. In addition to the consequences of the acute infection, COVID-19 is significantly impacting economies, social systems and political priorities. I will try to give a general overview of the current situation, starting from a medical standpoint and moving into the wider social consequences of this pandemic. I will highlight how the lack of attention to sex and gender can impact statistics, potential therapies and vaccines, livelihoods and the healthcare sector as a whole.

Differences in Physical and Mental Health of Older Adults over the Covid-19 Pandemic from Face-to-Face versus Hybrid Methods

Background/Purpose: As a result of the COVID-19 pandemic, changes in data collection methods have been introduced in research to ensure continuity despite physical distancing and lockdown restrictions. Our objective was to compare differences in physical and mental health of older adults participating in falls research using data collection methods pre-covid-19 pandemic (face-to-face) and during the pandemic (hybrid). Method(s): Individuals aged 60 years and over with at least one fall in the past 12 months, and controls with no history of falls in the past 12 months were recruited. Pre-pandemic, individuals were interviewed face-to-face exclusively, those interviews after the start of the pandemic were conducted virtually with physical assessments conducted face-to-face to minimize physical contact. Cognitive status, physical performance, psychological status, quality of life, physical activity, and social participation were measured. Result(s): Of the 145 participants of similar socio-demographic backgrounds, 69 were interviewed face-to-face, while 76 were assessed using a hybrid method. Differences were observed in presence of fall characteristics, with fewer fallers seeing a doctor and more fallers attending the emergency department after the start of the pandemic. After adjustment for baseline differences, participants interviewed using hybrid status had lower depression scores (OR (95%CI)=0.29(0.14-0.61)) and stress scores (OR(95%CI)=0.33(0.15-0.72)), but greater fear of falling (OR(95%CI)=2.16(1.04-4.48)) and reduced social participation (OR(95%CI)=2.64(1.20-5.79)). Conclusion(s): Alterations in data collection methods to overcome pandemic restrictions should take into consideration potential differences in individuals who agree to participate as well as the influence of major life events on the psychological status of participants. Copyright © 2022, Full Universe Integrated Marketing Limited. All rights reserved.

Short and medium-term outcomes of patients with solid cancer hospitalized with COVID-19 in Belgium according to cancer diagnosis and treatment characteristics

Background: Solid cancer is an independent prognostic factor for COVID-19 related mortality. Adverse prognostic factors in these patients include low performance status, lung cancer, advanced cancer stage and recent diagnosis. In this study, we further evaluated prognostic effects of cancer diagnosis and treatment variables and characterized changes in anticancer treatment plans due to COVID-19 diagnosis in a nation-wide cohort study. Methods: Patients with a history of solid cancer hospitalized with COVID-19 between March 2020 and February 2021 in one of the 20 participating institutions in Belgium were included. Patient demographics, comorbidities, COVID-19 hospitalization course and treatment, cancer and anticancer treatment characteristics, treatment changes due to COVID-19 and clinical outcomes in-hospital and during follow-up were retrospectively registered in a central database. The primary objective was to evaluate potential differences in 30-day and 3-month COVID-19-related mortality according to cancer and anticancer treatment characteristics. Results: A total of 946 patients (median age 73y, interquartile range 64-81y) were included. Pre-existing comorbidities were present in 90.1% of patients, and 21.9% had a history of > 1 malignancy. Half of the patients (n = 463, 49.3%) had received anticancer treatment ≤3 months before COVID-19 diagnosis (“active cancer”), of whom 286 (63.1%) in the non-curative setting. The overall 30-day and 3-month COVID-19- related mortality rates in this cohort were 21.4% (n = 178) and 24.1% (n = 194), respectively. COVID- related 3-month mortality was comparable in patients with active cancer (n = 96, 24.3%) and in patients with non-active cancer (n = 97, 24.0%), but within the first group COVID-related mortality was higher in those receiving systemic treatment in the non-curative (28.3%) versus the curative setting (15.2%). A change in the anticancer treatment plan due to COVID-19 was recorded in 148/463 patients with active cancer (32.0%). In patients with changes in systemic treatment plans (n = 146), treatment was delayed in 94 patients (in half of cases for > 1 month) and cancelled in 42 patients. The main reason for modifications in anti-cancer treatment was COVID-19 related complications (79.6%), followed by fear for/existence of anticancer treatment related toxicity (14.8%). Conclusions: Our nation-wide analysis in patients with solid cancer hospitalized with COVID-19 shows comparable 3-month mortality among patients who did and who did not receive anticancer treatment in the three months before COVID-19 diagnosis. Changes in anticancer treatment were very frequent in patients hospitalized with COVID-19. Further monitoring of the long-term impact of COVID-19-related changes to anticancer treatment plans is warranted.

Recruiting and retaining plasma donors in a voluntary non-remunerated context: Experiences from the Dutch 'Powerbank'

Background: Sanquin-the Dutch blood organization-collects both whole blood (WB) and plasma in a voluntary non-remunerated context. Increasing demand for plasma and a desire to depend less on foreign plasma made Sanquin step up their plasma collection game. Traditionally, Sanquin collects plasma in mixed whole blood and plasma centers. To increase efficiency, Sanquin opened a plasma-only center in the summer of 2020: the Powerbank. The Powerbank aims for high recruitment and retention rates by offering donors costefficient processes, high service levels, and a loyalty program. Aims: The aim of our study was to understand what kind of donors the Powerbank attracts and how they experience the Powerbank. Methods: To get a complete image of Powerbank donors and their experiences, we used a mixed methods approach combining a quantitative survey about characteristics of the plasma donor population with qualitative focus groups to provide more insight into donors' experiences. For the survey, we invited 4784 plasma donors from the Powerbank and a nearby mixed donation center, to examine potential differences between the two populations. We collected demographic information, that is, gender, age, education, ethnic background and working status. During six focus group discussions, we talked to 32 donors who had transferred from a mixed donation center to the Powerbank to reflect on their experiences. Topics included general impressions of the Powerbank, service level, perceptions of the loyalty program, and differences with the mixed center. Results: 646 Powerbank donors participated in the survey, as well as 780 donors from the mixed center. We found no differences between the two populations in terms of gender, education, household composition, or ethnic background. However, we did find that-compared to the mixed center-Powerbank donors were significantly younger, had made fewer prior donations, and were less often students or retirees. Donors in the focus group discussions were generally positive about the Powerbank. Positive points included the less clinical atmosphere, efficiency (specifically less waiting), the freedom of choice in the loyalty program, the service level, and the food. Donors had mixed feelings about the haemoglobin measurement (post donation) and the location (hard to find at first, but visible for passersby in the mall). Summary/Conclusions: Even though the COVID-19 pandemic had considerable impact on (plans for) recruitment and retention of donors at the Powerbank, we saw that donors were generally quite positive about the Powerbank. The somewhat younger, working donor population at the Powerbank and experiences of transferred donors seem to suggest that a new generation of donors could benefit from a visible location with a less clinical atmosphere where they are offered an efficient donation process and high service levels.

ASYMPTOMATIC SARS-CoV-2 INFECTION IS EXTREMELY COMMON among PEOPLE with HIV

Background: Asymptomatic COVID-19 is common among the general population, but little has been reported on this phenomenon among people with HIV (PWH) globally. Here we present data on a representative subset of 2,464 REPRIEVE participants with blood collected for COVID-19 serology from May 2020 to February 2021. Methods: REPRIEVE is an international primary atherosclerotic cardiovascular disease (ASCVD) prevention RCT of pitavastatin calcium vs. placebo among 7,770 PWH ages 40-75 on antiretroviral therapy (ART). Beginning in April 2020, targeted data on COVID-19 diagnosis and symptoms were collected as part of routine trial visits every 4 months, and blood was collected annually to assess SARS-CoV-2 serology. SARS-CoV-2 infection was defined as either presence of SARS-CoV-2 IgG or IgA RBD protein (anti-spike) antibodies or reporting of confirmed COVID-19 disease prior to the date of antibody sampling in the absence of prior COVID-19 vaccine receipt. We distinguished symptomatic from asymptomatic disease based on completed COVID-19 symptom questionnaire. Demographic, cardiometabolic, and HIV-specific data are described among those with symptomatic versus asymptomatic COVID-19 disease. Results: Participant characteristics (n=2464) included median age 53 years, 35% female sex, 47% Black or African American race, median CD4 count 649 c/mm3, and 97% with HIV VL <400 cp/mL. SARS-CoV-2 infection occurred in 318 persons (13%): 58 with clinical disease diagnosis and 260 with reactive Abs but no reported clinical disease. Of these persons, 304 completed symptom questionnaires: 120 (39%) reported at least 1 symptom of COVID-19 disease, but 184 (61%) reported no symptoms. PWH with asymptomatic infection were more likely to be from non-High Income Regions, of Black or African American race, and to be non-obese (Table). Median ASCVD risk score was <5% (low risk) for the two groups. Potential differences in symptomatic disease based on ART-regimen were noted, but no clinical differences between the groups for CD4 counts or HIV viral suppression were observed. Conclusion: Asymptomatic SARS-CoV-2 infection is very common among ART-treated PWH globally. With Ab testing, we determined that 61% of COVID-19 infections were asymptomatic in the REPRIEVE cohort, similar to rates reported in the general population. HIV clinicians must remain vigilant about COVID-19 testing among PWH to assure that asymptomatic cases are identified.

DOES ZYMOT SPERM SEPARATION IMPROVE EM- BRYO DEVELOPMENT OUTCOMES WHEN APPLIED TO ALL INFERTILITY PATIENTS COMPARED TO DENSITY GRADIENT WASHING OR SURGICALLYATTAINED SPERM?

OBJECTIVE: The ZyMot sperm separation device has proven favorable for use in elevated DNA fragmentation index (DFI) male factor patients, as an alternative to density gradient (DG) washing or surgically attained testicular sperm. In 2020, without fully understanding the infectivity and transmission potential of SARS-CoV2 in semen, a more liberal application of a timed ZyMot microfluidic swim-up was applied to our IVF patients to dilute out and minimize potential pathogens. This study aimed to evaluate whether the use of ZyMot sperm improved normal embryo development. MATERIALS AND METHODS: Retrospective analysis of PGT-A/ICSI cycles (N= 3219) between 2016-2020 was conducted to assessed fertilization rates (FR), blastocyst development/utilization rates (BUR) and genetic outcomes. Sperm preparations were performed per standard operating or manufacturer advised (i.e., ZyMot) procedures. Cumulus oocyte complexes were harvested 36h post-hCG, stripped and ICSI performed 3-5hr later. Zygotes were assessed at 16-18hr post-ICSI, and embryos cultured under humidified tri-gas incubation for up to 7 days. Blastocyst (BL) development as evaluated, and expanded BL or greater were biopsied on Days 5, 6 or 7. All BL were vitrified and genetics determinations for euploidy, aneuploidy and mosaicism were contrast. Applying Chi-squared analysis, we compared potential differences (p<0.05) between oocytes inseminated by DG wash (n=23,549), ZyMot wash (n=7,331) or testicular sperm (n=815). RESULTS: No difference in FR (76%), D5 BL formation (52-56%) or BUR (52-53%) was detected between DG and ZyMot washed sperm, respectively. Meanwhile, testicular sperm had a lower FR (70%;p<0.05), fewer BL forming on D5 (48%;p<0.05) and a lower overall BUR (41%;p<0.05). In addition, fewer testicular-derived BL were euploid (39%;p<0.05) with more aneuploidy (54%;p<0.05) than DG wash (50%, 39%;respectively) or ZyMot swim-up (45%, 37%;respectively) derived-embryos. No difference in potentially viable BL (Euploidy+Mosiac outcome) was observed between DG or ZyMot wash groups (63-64%). CONCLUSIONS: Application of the ZyMot device in the general IVF population offered no benefit to embryo development outcomes compared to standard sperm wash procedures. Our data does support that microfluidic separation of sperm using ZyMot for male factor patients with elevated DFI is a more favorable and cost-effective approach to surgically attaining testicular sperm when ejaculated sperm is possible. However, when insufficient motile and or morphologically normal sperm are available in an ejaculate further analysis is needed to elucidate the benefit of testicular biopsy treatment, as our assessments in this study may be biased by including men with non-obstructive azoospermia. IMPACT STATEMENT: The timed selection of morphologically normal, highly progressive sperm by ICSI, PVP-swim-out likely mimics the potential benefits the ZyMot device may offer infertile men with elevated sperm DNA fragmentation generating similar blastocyst development and euploidy outcomes.

An investigation of the use of dexrazoxane as a cardioprotectant in UK Teenage and Young Adult (TYA) Cancer Centres

Introduction: Around 1 in 10 childhood cancer survivors who receive an anthracycline develop a symptomatic cardiac event over time.1 Dexrazoxane, a free radical scavenger, has been shown to reduce surrogate markers of cardiac damage in children and young people receiving anthracycline chemotherapy.2 In February 2020, NHS England (NHSE) published a new clinical commissioning policy entitled: “Dexrazoxane for preventing cardiotoxicity in children and young people (under 25 years) receiving high-dose anthracyclines or related drugs for the treatment of cancer”.1 Given uncertainties regarding the robustness of the supporting data,1,2 a general unfamiliarity with the product and the timing of the publication of the policy (at the start of the COVID-19 pandemic) we hypothesised that these factors may all have impacted on the speed and degree of its adoption. Consequently we decided to undertake a survey of practice, with the aim of exploring awareness of the policy and use of the drug amongst UK TYA centres. Methods: A short questionnaire was designed using the www.onlinesurveys.ac.uk platform. The questionnaire was sent electronically to senior oncology/ haematology pharmacists from all 17 TYA Cancer Centres in the UK in March 2021 and was kept open for six weeks to allow centres sufficient time to respond. Responses were transferred to Microsoft Excel for data analysis. Results: Responses were received from all 17 UK TYA centres. All centres in England (n=13) were either very aware (69%) or somewhat aware (31%) of the dexrazoxane commissioning policy. The majority (three out of four) of the centres from the devolved nations were unaware of the policy. Five centres (29%) had used dexrazoxane as a cardioprotectant since February 2020 and a further five centres (29%) were considering its use. Reasons for not using the drug included: unconvinced by efficacy data (n=4), concerned re short and long-term side effects (n=3). Of those centres that had used the drug, three had only given it to 1-3 patients, one centre had given it to 7-9 patients and one centre had given it to >9 patients. None of the centres had a TYA Unit policy or guideline for the use dexrazoxane as a cardioprotectant, although two were in the process of writing one. Furthermore, although stipulated in the commissioning policy, only three out of five centres using the drug required MDT discussion prior to use. From a clinical perspective, there was a lack of consensus as to when in the treatment pathway to start the drug (i.e. with cycle one of chemotherapy or when a threshold dose had been reached). And from a practical perspective, concerns were raised about the short shelf-life of dexrazoxane and the workload implications for aseptic units. Conclusions: Despite generally good awareness of the dexrazoxane commissioning policy, use of the drug by TYA centres has been limited to date and clinical practice has not uniformly matched the recommendations contained within the policy. Further work is required to explore reasons for the slow and variable uptake and to also investigate potential differences in practice between TYA and paediatric centres.

Comparing Autopsy Thoracic Injury Patterns between In-Hospital CPR Patients Receiving LUCAS Device vs Manual Chest Compressions

Background: Current research comparing CPR-associated injuries between those receiving LUCAS device and manual CPR has primarily focused on patients who suffered out-of-hospital cardiac arrest. During the SARS-CoV-2 pandemic, more hospitals leveraged mechanical CPR devices to provide distant yet high quality chest compressions for in-hospital cardiac arrest (IHCA) patients. We sought to investigate autopsy thoracic injury patterns in in-hospital non-traumatic cardiac arrests, comparing traditional manual compressions with the mechanical LUCAS device compressions. Design: Autopsies were screened for a history of in-hospital cardiopulmonary resuscitation in the absence of prior traumatic injuries at a single, large quaternary care center from 1/1/2018 to 06/30/2021. 20 received LUCAS compressions and 40 received manual compressions. Student's T-Tests were used to compare means for continuous variables, while chi-squared and Fischer's exact tests were used for categorical variables. An alpha of 0.05 was chosen as the threshold for statistical significance. Results: A statistically significant decrease in the rate of sternal fractures and rate of multiple sternal fractures during mechanical CPR was found. A statistically significant increase in other soft tissue injuries, such as pleural wall or lung injuries was seen in mechanical CPR cases, while an increased rate of bilateral rib fractures was noted in manual compression cases. Conversely, no difference in the number or laterality of rib fractures were noted. There was no significant difference in age, biological sex, or rate of scoliosis or kyphosis between cohorts. Results are listed in table 1. (Table Presented) Little research has looked at the injury patterns of mechanical CPR in the IHCA patient population. These results point to a potential difference in thoracic injury patterns from manual compressions when compared to LUCAS device compressions. The statistically significant decrease in sternal fractures with mechanical compressions is noteworthy. Conversely, the increase in other soft tissue injury demands further examination. The decrease in bilateral rib fractures with LUCAS use suggests that placement of the device may play a role in the epidemiology of rib injuries, but not in the number of ribs injured. Further research should examine rib injuries in more detail, and quantify additional comorbidities in both survivors and non-survivors of cardiac arrest.

B-type and NT-proBNP natriuretic peptides as a prognostic marker of COVID-19 disease severity and outcome: Which one is the best performer?

Introduction: B-type natriuretic peptide (BNP) and Nterminal pro-B-type natriuretic peptide (NT-proBNP) are usually considered as equal diagnostic tools for heart failure. Increased concentrations of BNP and NT-proBNP in COVID-19 patients have already been reported. The aim of this study was to evaluate the usefulness of these markers and any potential difference between them in predicting COVID-19 prognosis.Materials and Methods: We retrospectively collected and analyzed data about 174 consecutive adult patients affected with COVID-19. The clinical course of COVID-19 before hospitalization and its related complications were also acquired. In particular, the presence of pre-existing diseases related to cardiac and pulmonary functions was recorded, alongside with diabetes and hypertension. BNP and NTproBNP of each patients were collected at admission in hospital. BNP plasma concentrations were measured by chemiluminescent microparticle immunoassay on the ARCHITECT i2000SR system (Abbott Laboratories, Wiesbaden, Germany). NT-proBNP was also measured on the ARCHITECT i2000SR system by using the Alere assay (Roche Diagnostics GmbH, Mannheim, Germany). Results: BNP and NT-proBNP values were higher in in-hospital non-surviving patients (p<0.001). Despite a high correlation obtained by Spearman's rank correlation coefficient between these two variables (rho =0.716, p<0.001), receiver operating characteristics (ROC) curve analysis showed that NT-proBNP (AUC =0.951) performed better (p=0.01) than BNP (AUC =0.777). Kaplan-Meier analysis was performed by dividing the population into groups, based on whether NT-proBNP and BNP concentrations at admission were higher than the cut-offs resulting from ROC curves. Both log rank tests resulted significant (p<0.001), in the group of patients with NT-proBNP admission values lower than the cutoff showing an absence of fatal outcome, whereas the subgroup of patients with BNP admission values lower than cut-off included 53.84% of all non-survivors of this study. Conclusion: NT-proBNP proved to be a better prognostic tool than BNP for fatal outcome in COVID-19 patients. In particular, our study highlighted that a value of NT-proBNP below the cut-off of 511 ng/L at admission led to no inhospital mortality in our population.