ABSTRACT
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).
ABSTRACT
Background: COVID-19 may be more severe in persons with HIV (PWH). However, underlying biological mechanisms associated with the development of COVID-19 and its clinical severity among antiretroviral therapy (ART) treated PWH are largely unknown. Therefore, we wished to evaluate temporal changes in plasma proteins following SARS-CoV-2 infection and identify pre-infection proteomic markers associated with future COVID-19. Method(s): We analyzed the data of clinical, antibody-confirmed COVID-19 ARTtreated PWH from the global Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE). Individuals were matched on geographic region, age, and sample timing to antibody-negative controls. For cases and controls, pre-COVID-19 pandemic specimens were obtained prior to January 2020 to assess temporal changes and baseline differences in protein expression in relationship to COVID-19 severity, using mixed effects models adjusted for false-discovery rate. Result(s): We compared 257 unique plasma proteins (Olink Proteomics) in 94 COVID-19 antibody-confirmed clinical cases and 113 matched antibody-negative controls, excluding COVID-19 vaccinated participants (median age 50 years, 73% male). 40% of cases were characterized as mild;60% moderate to severe. Median time from COVID-19 infection to follow-up sampling was 4 months. Temporal changes in protein expression differed based on COVID-19 disease severity. Among moderate to severe cases vs. controls, NOS3 increased, whereas ANG, CASP-8, CD5, GZMH, GZMB, ITGB2, and KLRD1 decreased. Higher baseline circulating concentrations of granzymes A, B and H (GZMA, GZMB and GZMH) were associated with the future development of moderate-severe COVID-19 in PWH and were related to immune function, including CD4, CD8 and the CD4/ CD8 ratio. Conclusion(s): We identified temporal changes in novel proteins in closely linked inflammatory, immune, and fibrotic pathways which may relate to COVID-19-related morbidity among ART-treated PWH. Further, we identified key granzyme proteins, serine proteases expressed by cytotoxic T lymphocytes and NK cells in response to foreign antigens, associated with future COVID-19 in PWH. Our results provide unique insights into the biological susceptibility and responses to COVID-19 infection in PWH. (Figure Presented).
ABSTRACT
The aim of the current study was to explore awareness and perceived helpfulness of mental health peer workers in Australia, and factors associated with knowledge and perceptions. As part of a broader longitudinal study of mental health in the COVID-19 pandemic, a survey of a nationally representative sample of N = 812 Australians was conducted in June 2020. Investigation of peer work comprised two areas: 1) whether they had accessed or were aware of peer workers;and 2) perceived helpfulness of peer workers. Only participants who indicated awareness of peer workers were asked about helpfulness. Seventy-five participants (9.2%) reported accessing a peer worker, but over half the sample were not aware they existed (n = 448). Mean helpfulness ratings indicated that participants believed peer work is somewhat or very helpful. In multivariate logistic regression analyses, age was associated with both greater awareness and perceived helpfulness;awareness was also associated with social impairment, and helpfulness with positive social support. Awareness of peer workers across the general community is limited, but peer workers are viewed favourably. Particularly in the context of increased need for mental support due to COVID-19, this suggests an opportunity to increase the workforce with an acceptable addition to clinical support.Copyright © 2022 The Authors
ABSTRACT
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.
ABSTRACT
As industry returns to work and restarts planning and execution of turnarounds and other maintenance projects, there will be regulatory, corporate and social responsibilities in order to safely restart and sustain activities. Major maintenance events and projects already bring complex challenges as multiple activities are carried out by numerous personnel and contractors, in a short duration of time. This risk is further amplified with the additional restrictions, challenges and complications posed by COVID-19. The key challenge for turnaround managers in current times is to ensure the safety of their personnel while delivering a successful turnaround. Through a detailed analysis and breakdown of the various stages of a turnaround, this paper attempts to answer one core question-How do you keep onsite personnel safe during turnarounds in the COVID-19 era? United Safety has developed a series of planning and prevention tools to help projects identify and implement robust actions that prevent the spread of COVID-19 onsite. These steps have been successfully implemented on site during a turnaround for a major Client in Canada. From additional precautions to new operating procedures, modifications were made at various stages including pre-planning, during the turnaround and post-turnaround stage to ensure the safety of onsite personnel. The result was an incident-free turnaround with zero recorded transmissions on site and a comprehensive COVID-19 Turnaround Response Plan. © 2021, Society of Petroleum Engineers.