Evaluating tixagevimab/cilgavimab prophylaxis in allogeneic haematopoietic cell transplantation recipients for COVID-19 prevention.

Allogeneic haematopoietic cell transplantation (allo-HCT) recipients exhibit an increased risk of COVID-19, particularly in the early post-transplant phase, due to insufficient vaccine responses. This retrospective study investigated the incidence of SARS-CoV-2 infection in allo-HCT recipients who received tixagevimab/cilgavimab pre-exposure prophylaxis (T/C PrEP) compared to those who did not. Logistic regression, adjusted for sex, age, SARS-CoV-2 vaccination status and immunosuppressive treatment, revealed a significant reduction in the likelihood of SARS-CoV-2 infection risk with T/C PrEP (adjusted odds ratio aOR = 0.26 [0.07, 0.91]). These findings suggest the potential efficacy of monoclonal antibody PrEP in protecting this vulnerable patient population from COVID-19.

Deciphering factors linked with reduced SARS-CoV-2 susceptibility in the Swiss HIV Cohort Study.

BACKGROUND: Factors influencing susceptibility to SARS-CoV-2 remain to be resolved. Using data of the Swiss HIV Cohort Study (SHCS) on 6,270 people with HIV (PWH) and serologic assessment for SARS-CoV-2 and circulating-human-coronavirus (HCoV) antibodies, we investigated the association of HIV-related and general parameters with SARS-CoV-2 infection. METHODS: We analyzed SARS-CoV-2 PCR-tests, COVID-19 related hospitalizations, and deaths reported to the SHCS between January 1, 2020 and December 31, 2021. Antibodies to SARS-CoV-2 and HCoVs were determined in pre-pandemic (2019) and pandemic (2020) bio-banked plasma and compared to HIV-negative individuals. We applied logistic regression, conditional logistic regression, and Bayesian multivariate regression to identify determinants of SARS-CoV-2 infection and Ab responses to SARS-CoV-2 in PWH. RESULTS: No HIV-1-related factors were associated with SARS-CoV-2 acquisition. High pre-pandemic HCoV antibodies were associated with a lower risk of subsequent SARS-CoV-2 infection and with higher SARS-CoV-2 antibody responses upon infection. We observed a robust protective effect of smoking on SARS-CoV-2-infection risk (aOR= 0.46 [0.38,0.56], p=2.6*10-14), which occurred even in previous smokers, and was highest for heavy smokers. CONCLUSIONS: Our findings of two independent protective factors, smoking and HCoV antibodies, both affecting the respiratory environment, underscore the importance of the local immune milieu in regulating susceptibility to SARS-CoV-2.

Bridging the gap: identifying factors impacting mRNA severe acute respiratory syndrome coronavirus 2 vaccine booster response in people with HIV-1.

OBJECTIVES: This study aimed to investigate the association of demographic and clinical characteristics, including HIV-specific parameters with the antibody response to a third dose of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in people with HIV-1 (PWH). DESIGN: Post hoc analysis of data collected during the observational extension of the COrona VaccinE tRiAL pLatform trial (COVERALL-2) nested into the Swiss HIV Cohort Study (SHCS). METHODS: Serological measurements were conducted on a total of 439 PWH who had received a third dose of either mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine. Antibody reactivity was assessed using the multifactorial ABCORA immunoassay that defines SARS-CoV-2 seroconversion and predicts neutralization activity. The association between log transformed antibody reactivity and various baseline factors, including vaccine type, demographics, immune and viral status, smoking status, comorbidities, infection history, and co-medication with chemotherapy and immunosuppressive drugs, was investigated using a multivariable linear regression model. RESULTS: Antibody response to third SARS-CoV-2 vaccination was significantly lower among PWH with CD4 + cell count less than 350 cells/µl [ratio of means 0.79; 95% confidence interval (CI) 0.65-0.95]. Having a detectable HIV-1 viral load at least 50 copies/ml and being on concurrent chemotherapy was associated with an overall lower humoral immune response (ratio of means 0.75; 95% CI 0.57-1.00 and 0.34; 95% CI 0.22-0.52, respectively). CONCLUSION: The study highlights the importance of optimal antiretroviral treatment for PWH, emphasizing the need for timely intervention to enhance the vaccine immunogenicity in this population. Moreover, it underscores the significance of sequential mRNA vaccination and provides important evidence for informing vaccine guidelines.

Antibody response to a third SARS-CoV-2 vaccine dose in recipients of an allogeneic haematopoietic cell transplantation.

Allogeneic haematopoietic cell transplantation (allo-HCT) recipients show impaired antibody (Ab) response to a standard two-dose vaccination against severe acute respiratory syndrome coronavirus-2 and currently a third dose is recommended as part of the primary vaccination regimen. By assessing Ab titres 1 month after a third mRNA vaccine dose in 74 allo-HCT recipients we show sufficient neutralisation activity in 77% of the patients. Discontinuation of immunosuppression before the third vaccine led to serological responses in 50% of low responders to two vaccinations. Identifying factors that might contribute to better vaccine responses in allo-HCT recipients is critical to optimise current vaccination strategies.

Antibody Response in Immunocompromised Patients After the Administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine BNT162b2 or mRNA-1273: A Randomized Controlled Trial.

BACKGROUND: BNT162b2 by Pfizer-BioNTech and mRNA-1273 by Moderna are the most commonly used vaccines to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Head-to-head comparison of the efficacy of these vaccines in immunocompromised patients is lacking. METHODS: Parallel, 2-arm (allocation 1:1), open-label, noninferiority randomized clinical trial nested into the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. People living with human immunodeficiency virus (PLWH) or solid organ transplant recipients (SOTR; ie, lung and kidney) from these cohorts were randomized to mRNA-1273 or BNT162b2. The primary endpoint was antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain (Elecsys Anti-SARS-CoV-2 immunoassay, Roche; cutoff ≥0.8 units/mL) 12 weeks after first vaccination (ie, 8 weeks after second vaccination). In addition, antibody response was measured with the Antibody Coronavirus Assay 2 (ABCORA 2). RESULTS: A total of 430 patients were randomized and 412 were included in the intention-to-treat analysis (341 PLWH and 71 SOTR). The percentage of patients showing an immune response was 92.1% (95% confidence interval [CI]: 88.4-95.8; 186/202) for mRNA-1273 and 94.3% (95% CI: 91.2-97.4; 198/210) for BNT162b2 (difference: -2.2%; 95% CI: -7.1 to 2.7), fulfilling noninferiority of mRNA-1273. With the ABCORA 2 test, 89.1% had an immune response to mRNA-1273 (95% CI: 84.8-93.4; 180/202) and 89.5% to BNT162b2 (95% CI: 85.4-93.7; 188/210). Based on the Elecsys test, all PLWH had an antibody response (100.0%; 341/341), whereas for SOTR, only 60.6% (95% CI: 49.2-71.9; 43/71) had titers above the cutoff level. CONCLUSIONS: In immunocompromised patients, the antibody response of mRNA-1273 was noninferior to BNT162b2. PLWH had in general an antibody response, whereas a high proportion of SOTR had no antibody response.

Women with HIV transitioning through menopause: Insights from the Swiss HIV Cohort Study (SHCS).

OBJECTIVES: We aimed to assess prevalence and age at menopause, identify factors associated with early menopause and explore the provision and utilization of healthcare in women living with HIV in Switzerland. METHODS: This was a retrospective Swiss HIV Cohort Study analysis from January 2010 to December 2018. Descriptive statistics to characterise the population and menopause onset. Logistic regression analysis to identify risk factors for early menopause. RESULTS: Of all women in the SHCS, the proportion of postmenopausal women tripled from 11.5% (n = 274) in 2010 to 36.1% (n = 961) in 2018. The median age at menopause was 50 years. Early menopause (< 45 years) occurred in 115 (10.2%) women and premature ovarian insufficiency (POI) (< 40 years) in 23 (2%) women. Early menopause was associated with black ethnicity (52.2% vs. 21.6%, p < 0.001), but not with HIV acquisition mode, CDC stage, viral suppression, CD4 cell count, hepatitis C, smoking or active drug use. While 92% of the postmenopausal women underwent a gynaecological examination during the 36 months before menopause documentation, only 27% received a bone mineral density measurement within 36 months after the last bleed and 11% were on hormone replacement therapy at the time of menopause documentation. CONCLUSIONS: The median age of women living with HIV at menopause is around 2 years lower than that reported for HIV-negative women in Switzerland. HIV care providers need to adapt their services to the requirements of the increasing number of women living with HIV transitioning through menopause. They should be able to recognize menopause-associated symptoms and improve access to bone mineral density measurement as well as hormone replacement therapy.

Antibody Response to SARS-CoV-2 Vaccination in Patients following Allogeneic Hematopoietic Cell Transplantation.

Vaccines against SARS-CoV-2 have been rapidly approved. Although pivotal studies were conducted in healthy volunteers, little information is available on the safety and efficacy of mRNA vaccines in immunocompromised patients, including recipients of allogeneic hematopoietic cell transplantation (allo-HCT). Here we used a novel assay to analyze patient- and transplantation-related factors and their influence on immune responses to SARS-CoV-2 vaccination over an extended period (up to 6 months) in a large and homogenous group of allo-HCT recipients at a single center in Switzerland. We examined longitudinal antibody responses to SARS-CoV-2 vaccination with BNT162b2 (BioNTech/Pfizer) and mRNA-1273 (Moderna) in 110 allo-HCT recipients and 86 healthy controls. Seroprofiling recording IgG, IgA, and IgM reactivity against SARS-CoV-2 antigens (receptor-binding domain, spike glycoprotein subunits S1 and S2, and nucleocapsid protein) was performed before vaccination, before the second dose, and at 1, 3, and 6 months after the second dose. Patients were stratified to 3 groups: 3 to 6 months post-allo-HCT, 6 to 12 months post-allo-HCT, and >12 months post-allo-HCT. Patients in the 3 to 6 months and 6 to 12 months post-allo-HCT groups developed significantly lower antibody titers after vaccination compared with patients in the >12 months post-allo-HCT group and healthy controls (P < .001). Within the cohort of allo-HCT recipients, patients age >65 years (P = .030), those receiving immunosuppression for prevention or treatment of graft-versus-host disease (GVHD) (P = .033), and patients with relapsed disease (P = .014) displayed low humoral immune responses to the vaccine. In contrast, the intensity of the conditioning regimen, underlying disease (myeloid/lymphoid/other), and presence of chronic GVHD had no impact on antibody levels. Antibody titers achieved the highest levels at 1 month after the second dose of the vaccine but waned substantially in all transplantation groups and healthy controls over time. This analysis of long-term vaccine antibody response is of critical importance to allo-HCT recipients and transplant physicians to guide treatment decisions regarding revaccination and social behavior during the SARS-CoV-2 pandemic.

Subacute cerebellar ataxia following respiratory symptoms of COVID-19: a case report.

BACKGROUND: Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is spreading globally and causes most frequently fever and respiratory symptoms, i.e. Coronavirus disease 2019 (COVID-19), however, distinct neurological syndromes associated with SARS-CoV-2 infection have been described. Among SARS-CoV-2-infections-associated neurological symptoms fatigue, headache, dizziness, impaired consciousness and anosmia/ageusia are most frequent, but less frequent neurological deficits such as seizures, Guillain-Barré syndrome or ataxia may also occur. CASE PRESENTATION: Herein we present a case of a 62-year-old man who developed a subacute cerebellar syndrome with limb-, truncal- and gait ataxia and scanning speech 1 day after clinical resolution of symptomatic SARS-CoV-2 infection of the upper airways. Apart from ataxia, there were no signs indicative of opsoclonus myoclonus ataxia syndrome or Miller Fisher syndrome. Cerebral magnetic resonance imaging showed mild cerebellar atrophy. SARS-CoV-2 infection of the cerebellum was excluded by normal cerebrospinal fluid cell counts and, most importantly, absence of SARS-CoV-2 RNA or intrathecal SARS-CoV-2-specific antibody production. Other causes of ataxia such as other viral infections, other autoimmune and/or paraneoplastic diseases or intoxication were ruled out. The neurological deficits improved rapidly after high-dose methylprednisolone therapy. CONCLUSIONS: The laboratory and clinical findings as well as the marked improvement after high-dose methylprednisolone therapy suggest a post-infectious, immune-mediated cause of ataxia. This report should make clinicians aware to consider SARS-CoV-2 infection as a potential cause of post-infectious neurological deficits with an atypical clinical presentation and to consider high-dose corticosteroid treatment in case that a post-infectious immune-mediated mechanism is assumed.

Does respiratory co-infection facilitate dispersal of SARS-CoV-2? investigation of a super-spreading event in an open-space office.

BACKGROUND: Super-spreaders are individuals infecting disproportionately large numbers of contacts. They probably play a crucial role in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe a super-spreading event within a team working in an open-space office and investigate factors potentially having facilitated SARS-CoV-2 transmission. METHODS: In this retrospective cohort study, semi-structured telephone interviews with all team members were carried out to identify symptoms, contacts, and adherence to basic hygiene measures. During site visits, we gathered information about workplace and seating arrangements. The secondary attack rate in office and households was calculated. Potential respiratory viral co-infections were assessed by multiplex PCR. SARS-CoV-2 whole-genome sequencing was performed using a tiled-amplicon sequencing approach. RESULTS: Of 13 team members, 11 fell ill with Coronavirus disease 2019 (COVID-19). Due to the sequence of events and full genome sequence data, one person was considered the index case for this outbreak, directly infecting 67 to 83% of the teammates. All team members reported repetitive close contacts among themselves during joint computer work, team meetings and a "Happy Birthday" serenade. Two individuals shared nuts and dates. The arrangement of the office and meeting rooms precluded sufficient adherence to physical distancing. The index case and a further individual were diagnosed with an adenovirus serotype 4 co-infection. CONCLUSION: We identified several environmental and behavioral factors that probably have facilitated the transmission of SARS-CoV-2. The relevance of the adenovirus co-infection remains unclear and merits further investigation.

A cluster of scedosporiosis in lung transplant candidates and recipients: The Zurich experience and review of the literature.

Scedosporium species are fungal pathogens increasingly recognized in cystic fibrosis (CF). They can cause multiresistant, life-threatening infections that are of particular concern in CF patients undergoing lung transplantation, as optimal treatment remains unclear. Here, we describe our Zurich experience of CF patients with Scedosporium infection. Disseminated infection occurred in one patient after transplantation and was successfully treated. We propose a step-by-step approach to treat candidates with colonization, and discuss our cases in the context of the current literature.

Therapeutic antibodies in HIV treatment--classical approaches to novel advances.

Therapeutic antibodies have evolved into an important drug class and have achieved considerable success in combating cancers and autoimmune diseases. Although their potential in the treatment of viral infections has not yet been fully explored, recently established approaches have the potential to aid the development of HIV specific antibody therapies. Antibody engineering has led to improvements in antibody isolation and increases in antibody efficacy and potency. Strategies have been developed to tailor Fc recruitment of effector functions, and conjugation of monoclonals to toxins endows them with the ability to mediate destruction of specific target cells. These technical advances introduce the possibility of designing a therapy to target and clear cells infected with a broad range of HIV strains and recommend some hypothetical clinical settings in which advanced antibody therapeutics could be employed in prophylaxis or therapy for HIV infection.