Ganciclovir (GCV)‐resistant cytomegalovirus (CMV) infection is a common problem among solid organ transplant (SOT) recipients without prior CMV immunity (CMV D+/R−). GCV‐resistant CMV represents a ...particular challenge for CMV management. Letermovir is a recently licensed antiviral agent for primary CMV prophylaxis in allogenic hematopoietic stem cell transplant (HSCT) recipients. Given the favorable safety profile and its oral bioavailability letermovir may be considered a valuable off‐label option for secondary prophylaxis of GCV‐resistant CMV in SOT recipients. Here, we describe our experience with letermovir as secondary prophylaxis for GCV‐resistant CMV in two renal transplant recipients and review the literature in regard of previously published cases. Letermovir resistance emerged after a few months of secondary prophylaxis in the two renal transplant recipients. In both cases, the previously described UL56 C325Y letermovir resistance mutation was detected. In vitro studies of letermovir suggest a relatively low genetic barrier to resistance. Therefore, caution is warranted when using letermovir as secondary prophylaxis for GCV‐resistant CMV infection.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background
Serological tests are a powerful tool in the monitoring of infectious diseases and the detection of host immunity. However, manufacturers often provide diagnostic accuracy data generated ...through biased studies, and the performance in clinical practice is essentially unclear.
Objectives
We aimed to determine the diagnostic accuracy of various serological testing strategies for (a) identification of patients with previous coronavirus disease‐2019 (COVID‐19) and (b) prediction of neutralizing antibodies against SARS‐CoV‐2 in real‐life clinical settings.
Methods
We prospectively included 2573 consecutive health‐care workers and 1085 inpatients with suspected or possible previous COVID‐19 at a Swiss University Hospital. Various serological immunoassays based on different analytical techniques (enzyme‐linked immunosorbent assays, ELISA; chemiluminescence immunoassay, CLIA; electrochemiluminescence immunoassay, ECLIA; and lateral flow immunoassay, LFI), epitopes of SARS‐CoV‐2 (nucleocapsid, N; receptor‐binding domain, RBD; extended RBD, RBD+; S1 or S2 domain of the spike S protein, S1/S2), and antibody subtypes (IgG, pan‐Ig) were conducted. A positive real‐time PCR test from a nasopharyngeal swab was defined as previous COVID‐19. Neutralization assays with live SARS‐CoV‐2 were performed in a subgroup of patients to assess neutralization activity (n = 201).
Results
The sensitivity to detect patients with previous COVID‐19 was ≥85% in anti‐N ECLIA (86.8%) and anti‐S1 ELISA (86.2%). Sensitivity was 84.7% in anti‐S1/S2 CLIA, 84.0% in anti‐RBD+LFI, 81.0% in anti‐N CLIA, 79.2% in anti‐RBD ELISA, and 65.6% in anti‐N ELISA. The specificity was 98.4% in anti‐N ECLIA, 98.3% in anti‐N CLIA, 98.2% in anti‐S1 ELISA, 97.7% in anti‐N ELISA, 97.6% in anti‐S1/S2 CLIA, 97.2% in anti‐RBD ELISA, and 96.1% in anti‐RBD+LFI.
The sensitivity to detect neutralizing antibodies was ≥85% in anti‐S1 ELISA (92.7%), anti‐N ECLIA (91.7%), anti‐S1/S2 CLIA (90.3%), anti‐RBD+LFI (87.9%), and anti‐RBD ELISA (85.8%). Sensitivity was 84.1% in anti‐N CLIA and 66.2% in anti‐N ELISA. The specificity was ≥97% in anti‐N CLIA (100%), anti‐S1/S2 CLIA (97.7%), and anti‐RBD+LFI (97.9%). Specificity was 95.9% in anti‐RBD ELISA, 93.0% in anti‐N ECLIA, 92% in anti‐S1 ELISA, and 65.3% in anti‐N ELISA. Diagnostic accuracy measures were consistent among subgroups.
Conclusions
The diagnostic accuracy of serological tests for SARS‐CoV‐2 antibodies varied remarkably in clinical practice, and the sensitivity to identify patients with previous COVID‐19 deviated substantially from the manufacturer's specifications. The data presented here should be considered when using such tests to estimate the infection burden within a specific population and determine the likelihood of protection against re‐infection.
This large prospective cross‐sectional study determines the diagnostic accuracy of various serological testing strategies for identification of patients with previous COVID‐19 and prediction of neutralizing antibodies against SARS‐CoV‐2 in real‐life clinical settings. The diagnostic accuracy in detecting patients with previous COVID‐19 was high in anti‐N ECLIA and anti‐S1 ELISA (sensitivity ≥85%; specificity ≥97%). The accuracy in detecting neutralizing antibodies was high in anti‐S1/S2 CLIA and anti‐RBD+LFI (sensitivity ≥85%; specificity ≥97%).Abbreviations: CLIA, chemiluminescence immunoassay; COVID‐19, coronavirus disease 2019; ECLIA, electrochemiluminescence immunoassay; ELISA, enzyme‐linked immunosorbent assay; LFI, lateral flow immunoassay; N, nucleoprotein; RBD, receptor‐binding domain of the SARS‐CoV‐2 spike glycoprotein; RBD+, extended receptor‐binding domain of the SARS‐ CoV‐2 spike glycoprotein; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; S1/2, domain 1 or 2 of the SARS‐CoV‐2 spike glycoprotein
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Although mRNA-based vaccines against SARS-CoV-2 induce a robust immune response and prevent infections and hospitalizations, there are limited data on the antibody response in individuals with ...humoral immunodeficiency. The aim of this study was to evaluate the humoral immune response after two vaccine doses with BNT162b2 or mRNA-1273 in patients with humoral immunodeficiency disease.
This cross-sectional study assessed 39 individuals with hypogammaglobulinemia under immunoglobulin replacement therapy. IgG anti-SARS-CoV-2 spike protein antibodies (anti-S) were measured 4 weeks to 4 months after two doses of an mRNA vaccine against SARS-CoV-2. The proportion of patients, who developed a humoral immune response to the spike protein were evaluated and compared to 19 healthy controls.
After vaccination with two vaccine doses, 26/39 patients (66.7%) with humoral immunodeficiency disease and all healthy controls developed anti-S. In subjects with baseline IgG <3 g/l, only 1/5 (20%) showed a humoral immune response. 10 out of 26 with CVID (38.5%) and 7/9 under immunosuppressive drugs (77.8%) developed no immune response (13 subjects with no response) compared to 0/19 in healthy controls. Subgroup analysis in patients without immunosuppressive drugs revealed lower anti-S in patients with moderate to severe humoral immunodeficiency disease: baseline IgG <3 g/l: 12.0 AU/ml (95%CI 12.0-125.0), baseline IgG 3-5 g/l: 99.9 AU/ml (95%CI 14.4-400.0), baseline IgG >5 g/l: 151.5 AU/ml (95%CI 109.0-400.0), healthy controls 250.0 AU/ml (95%CI 209.0-358.0), p = 0.007.
In most patients with mild to moderate humoral immunodeficiency we found only slightly lower anti-S antibodies compared with healthy controls after two vaccine doses with BNT162b2 and mRNA-1273. However, in patients with a decreased baseline IgG below 3 g/l and/or under immunosuppressive drugs, we found severely impaired humoral immune responses.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
Improving the understanding of the patterns of quantitative hepatitis B surface antigen (qHBsAg) trajectories associated with HBsAg loss is important in light of novel anti‐hepatitis B ...virus agents being developed. We evaluated long‐term qHBsAg trajectories in persons with HIV and HBV during tenofovir‐containing antiretroviral therapy in the Swiss HIV Cohort Study.
Methods
We included 29 participants with and 29 without HBsAg loss, defined as qHBsAg <0.05 IU/mL. We assessed qHBsAg decline during therapy in both groups and used agglomerative hierarchical clustering to identify different qHBsAg trajectory profiles in persons with HBsAg loss.
Results
The median follow‐up time was 11.9 years (IQR 8.4–14.1), and the median time to HBsAg loss was 48 months (IQR 12–96). Among participants with HBsAg loss, 79% had a qHBsAg decline ≥1 log10 IU/mL 2 years after starting tenofovir. The trajectories in qHBsAg levels during tenofovir therapy were heterogeneous, characterized by five distinct profiles. Among participants without HBsAg loss, only 7% had a qHBsAg decline ≥1 log10 IU/ml after 2 years.
Conclusions
Most persons with HIV who experienced HBsAg loss had an early decline in qHBsAg levels, with diverse trajectories during long‐term tenofovir therapy. In persons without HBsAg loss, qHBsAg levels remained remarkably stable over time.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Human adenoviruses (HAdVs) are highly contagious pathogens of clinical importance, especially among the pediatric population. Studies on comparative viral genomic analysis of cases associated with ...severe and mild infections due to HAdV are limited. Using whole-genome sequencing (WGS), we investigated whether there were any differences between circulating HAdV strains associated with severe infections (meningitis, sepsis, convulsion, sudden infant death syndrome, death, and hospitalization) and mild clinical presentations in pediatric patients hospitalized between the years 1998 and 2017 in a tertiary care hospital group in Bern, Switzerland covering a population base of approx. 2 million inhabitants. The HAdV species implicated in causing severe infections in this study included HAdV species C genotypes (HAdV1, HAdV2, and HAdV5). Clustering of the HAdV whole-genome sequences of the severe and mild cases did not show any differences except for one sample (isolated from a patient presenting with sepsis, meningitis, and hospitalization) that formed its own cluster with HAdV species C genotypes. This isolate showed intertypic recombination events involving four genotypes, had the highest homology to HAdV89 at complete genome level, but possessed the fiber gene of HAdV1, thereby representing a novel genotype of HAdV species C. The incidence of potential recombination events was higher in severe cases than in mild cases. Our findings confirm that recombination among HAdVs is important for molecular evolution and emergence of new strains. Therefore, further research on HAdVs, particularly among susceptible groups, is needed and continuous surveillance is required for public health preparedness including outbreak investigations.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•High hopes are placed on SARS-CoV-2 rapid antigen tests•Their diagnostic accuracy in clinical settings is essentially unclear•A large diagnostic accuracy study was conducted in a real-life clinical ...setting•The diagnostic accuracy of the Roche/SD Biosensor test was 65%•Their application might lead to a considerable number of false-negative test results
Laboratory tests are a mainstay in managing the COVID-19 pandemic, and high hopes are placed on rapid antigen tests. However, the accuracy of rapid antigen tests in real-life clinical settings is unclear because adequately designed diagnostic accuracy studies are essentially lacking.
The aim of this study was to assess the accuracy of a rapid antigen test in diagnosing SARS-CoV-2 infection in a primary/secondary care testing facility.
Consecutive individuals presenting at a COVID-19 testing facility affiliated to a Swiss University Hospital were recruited (n = 1465%). Nasopharyngeal swabs were obtained, and the Roche/SD Biosensor rapid antigen test was conducted in parallel with two real-time PCR tests (reference standard).
Among the 1465 patients recruited, RT-PCR was positive in 141 individuals, corresponding to a prevalence of 9.6%. The Roche/SD Biosensor rapid antigen test was positive in 94 patients (6.4%), and negative in 1368 individuals (93.4%; insufficient sample material in 3 patients). The overall sensitivity of the rapid antigen test was 65.3% (95% confidence interval CI 56.8–73.1), the specificity was 99.9% (95% CI 99.5–100.0). In asymptomatic individuals, the sensitivity was 44.0% (95% CI 24.4–65.1).
The accuracy of the SARS-CoV-2 Roche/SD Biosensor rapid antigen test in diagnosing SARS-CoV-2 infections in a primary/secondary care testing facility was considerably lower compared with the manufacturer's data. Widespread application in such a setting might lead to a considerable number of individuals falsely classified as SARS-CoV-2 negative.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Liver transplant recipients show suboptimal vaccine-elicited immune responses to severe acute respiratory coronavirus 2 (SARS-CoV-2) vaccination. This study aimed to assess real-world data on ...SARS-CoV-2 antibodies after the second and third SARS-CoV-2 vaccination in liver transplant recipients in Switzerland.
We enrolled liver transplant recipients who attended regular follow-up visits between 01/07/2021 and 30/04/2022 at the outpatient clinic of the Department of Visceral Surgery and Medicine at Bern University Hospital, Switzerland. Following the Swiss Federal Office of Public Health recommendations, we measured SARS-CoV-2 anti-spike IgG antibodies in 117 liver transplant recipients ≥4 weeks after the second SARS-CoV-2 mRNA vaccination from 07/2021-04/2022. In case of antibody levels of <100 AU/ml, patients received a third vaccination and antibodies were re-measured. Patients with antibody levels of >100 AU/ml were defined as "responders", those with 12-100 AU/ml as "partial responders" and those with <12 AU/ml as "non-responders".
After two vaccinations, 36/117 (31%) were responders, 42/117 (36%) were partial responders and 39/117 (33%) were non-responders. The humoral immune response improved significantly after the third vaccination, resulting in 31/55 (56%) responders among the previous partial or non-responders. A total of 26 patients developed COVID-19, of whom two had a moderate or severe course (both non-responders after three doses).
One third of liver transplant recipients showed an optimal response following two vaccinations; a third dose achieved a complete antibody response in more than half of partial and non-responders. We observed only one severe course of COVID-19 and no deaths from COVID-19 in the vaccinated liver transplant recipients.
BACKGROUND: Healthcare workers are more frequently exposed to SARS-CoV-2 than the general population. Little is known about healthcare settings outside of hospitals. We studied the seroprevalence of ...SARS-CoV-2 among healthcare workers in outpatient facilities and retirement or nursing homes in the Canton of Solothurn, Switzerland in the first wave of the COVID-19 pandemic.
METHODS: Longitudinal seroprevalence study among healthcare workers with examinations at baseline and 2 months between June and September 2020. The Abbott SARS-CoV-2 IgG and Liaison/Diasorin SARS-CoV-2 S1/S2 IgG assay were used to detect antibodies against SARS-CoV-2. All participants provided demographic information. We report descriptive statistics and calculated the seroprevalence with 95% confidence intervals.
RESULTS: We included 357 healthcare workers; their median age was 43 years (interquartile range 29–54), and 315 (88.2%) were female. Forty-nine (13.7%) were physicians, 87 (24.4%) practice assistants and 221 (61.9%) nurses. Overall seroprevalence among healthcare workers in outpatient facilities and retirement or nursing homes was 3.4% (12/357). The 12 seropositive healthcare workers were all nurses (12/221, 5.5%); 11 worked at retirement or nursing homes and one at the hospital's outpatient clinic. Symptoms such as loss of smell or taste, shortness of breath, and fever were more prevalent among seropositive healthcare workers than seronegative healthcare workers. No close contact had detectable antibodies against SARS-CoV-2.
CONCLUSIONS: Seroprevalence among healthcare workers was low, but higher among nursing staff of retirement or nursing homes. Healthcare workers at private practices were able to protect themselves well during the first wave of the COVID-19 pandemic.
Background: Due to B-cell aplasia following CAR-T-cell therapy, patients are at risk of severe SARS-CoV-2 course. Methods: COVID-19 vaccines were assessed by IgG antibody tests against SARS-CoV-2 ...spike protein (anti-S1/S2). Vaccination procedures: group (1): CAR-T-cells followed by two to four vaccine doses; group (2): Two vaccine doses prior to CAR-T-cells, followed by doses 3 or 4. Results: In group 1 (n = 32), 7/30 patients (23.2%) had positive antibody tests after a second dose, 9/23 (39.1%) after a third dose, and 3/3 patients after a fourth dose. A third dose led to seroconversion in 5 of 21 patients (23.8%) with available data, while a fourth dose did so in 2/3 patients. Higher B-cells (AUC: 96.2%, CI: 89–100, p = 0.0006) and lower CAR-T-cell copies (AUC: 77.3%, CI: 57–97, p = 0.0438) were predictive of positive humoral vaccine response. In group 2 (n = 14), 6/14 patients (42.9%) had a positive antibody test after a second dose, 3/8 patients (37.5%) after a third dose, and 3/4 patients after a fourth dose. A third dose led to seroconversion in 1/8 patients (12.5%), while a fourth dose did so in 3/4 patients. Conclusion: Additional vaccine doses increased seroconversion rates whilst high B-cell counts and low CAR-T-cell copy numbers were associated with positive antibody response.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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