Circulating HBV RNA and hepatitis B core-related antigen trajectories in persons with HIV/HBV coinfection and HBsAg loss on tenofovir therapy.

BACKGROUND: We evaluated long-term trajectories of circulating hepatitis B virus (HBV)-RNA and hepatitis B core-related antigen (HBcrAg) in persons with and without hepatitis B surface antigen (HBsAg) loss during tenofovir therapy in the Swiss HIV Cohort Study. METHODS: We included 29 persons with HIV (PWH) with HBsAg loss and 29 matched PWH without loss. We compared HBV-RNA and HBcrAg decline and assessed the cumulative proportions with undetectable HBV-RNA and HBcrAg levels during tenofovir therapy using Kaplan-Meier estimates. RESULTS: HBsAg loss occurred after a median of 4 years (IQR 1 - 8). All participants with HBsAg loss achieved suppressed HBV-DNA and undetectable HBV-RNA preceding undetectable qHBsAg levels, whereas 79% achieved negative HBcrAg. In comparison, 79% of the participants without HBsAg loss achieved undetectable HBV-RNA and 48% negative HBcrAg. After two years on tenofovir, an HBV RNA decline ≥1 log10 copies/ml had 100% sensitivity and 36.4% specificity for HBsAg loss, whereas an HBcrAg decline ≥1 log10 U/ml had 91.0% sensitivity and 64.5% specificity. CONCLUSIONS: HBV-RNA suppression preceded undetectable qHBsAg levels, and had high sensitivity but low specificity for HBsAg loss during tenofovir therapy in PWH. HBcrAg remained detectable in approximately 20% of persons with, and 50% of persons without HBsAg loss.

Immune Monitoring-Guided Versus Fixed Duration of Antiviral Prophylaxis Against Cytomegalovirus in Solid-Organ Transplant Recipients: A Multicenter, Randomized Clinical Trial.

BACKGROUND: The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. METHODS: In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. RESULTS: Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001). CONCLUSIONS: Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection. CLINICAL TRIALS REGISTRATION: NCT02538172.

Long-term quantitative hepatitis B surface antigen (HBsAg) trajectories in persons with and without HBsAg loss on tenofovir-containing antiretroviral therapy.

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.

Hepatitis B Virus (HBV) Replication During Tenofovir Therapy Is Frequent in Human Immunodeficiency Virus/HBV Coinfection.

In the Swiss HIV Cohort Study, 61 of 222 (27%) HIV-suppressed persons with chronic hepatitis B virus (HBV) infection had HBV replication after 2 years on tenofovir, of whom 77% were suppressed thereafter. Self-reported adherence to therapy and HBV viral load at tenofovir initiation were predictors of persistent replication.

Hepatitis delta infection among persons living with HIV in Europe.

BACKGROUND AND AIMS: A high prevalence of hepatitis delta virus (HDV) infection, the most severe form of viral hepatitis, has been reported among persons living with HIV (PLWH) in Europe. We analysed data from a large HIV cohort collaboration to characterize HDV epidemiological trends across Europe, as well as its impact on clinical outcomes. METHODS: All PLWH with a positive hepatitis B surface antigen (HBsAg) in the Swiss HIV Cohort Study and EuroSIDA between 1988 and 2019 were tested for anti-HDV antibodies and, if positive, for HDV RNA. Demographic and clinical characteristics at initiation of antiretroviral therapy were compared between HDV-positive and HDV-negative individuals using descriptive statistics. The associations between HDV infection and overall mortality, liver-related mortality as well as hepatocellular carcinoma (HCC) were assessed using cumulative incidence plots and cause-specific multivariable Cox regression. RESULTS: Of 2793 HBsAg-positive participants, 1556 (56%) had stored serum available and were included. The prevalence of HDV coinfection was 15.2% (237/1556, 95% confidence interval [CI]: 13.5%-17.1%) and 66% (132/200) of HDV-positive individuals had active HDV replication. Among persons who inject drugs (PWID), the prevalence of HDV coinfection was 50.5% (182/360, 95% CI: 45.3%-55.7%), with similar estimates across Europe, compared to 4.7% (52/1109, 95% CI: 3.5%-5.9%) among other participants. During a median follow-up of 10.8 years (interquartile range 5.6-17.8), 82 (34.6%) HDV-positive and 265 (20.1%) HDV-negative individuals died. 41.5% (34/82) of deaths were liver-related in HDV-positive individuals compared to 17.7% (47/265) in HDV-negative individuals. HDV infection was associated with overall mortality (adjusted hazard ratio 1.6; 95% CI 1.2-2.1), liver-related death (2.9, 1.6-5.0) and HCC (6.3, 2.5-16.0). CONCLUSION: We found a very high prevalence of hepatitis delta among PWID across Europe. Among PLWH who do not inject drugs, the prevalence was similar to that reported from populations without HIV. HDV coinfection was associated with liver-related mortality and HCC incidence.

Serological testing for SARS-CoV-2 antibodies in clinical practice: A comparative diagnostic accuracy study.

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.

Meningitis, meningoencephalitis and encephalitis in Bern: an observational study of 258 patients.

BACKGROUND: Depending on geographic location, causes of encephalitis, meningoencephalitis and meningitis vary substantially. We aimed to identify the most frequent causes, clinical presentation and long-term outcome of encephalitis, meningoencephalitis and meningitis cases treated in the Inselspital University Hospital Bern, Switzerland. METHODS: In this monocentric, observational study, we performed a retrospective review of clinical patient records for all patients treated within a 3-year period. Patients were contacted for a telephone follow-up interview and to fill out questionnaires, especially related to disturbances of sleep and wakefulness. RESULTS: We included 258 patients with the following conditions: encephalitis (18%), nonbacterial meningoencephalitis (42%), nonbacterial meningitis (27%) and bacterial meningoencephalitis/meningitis (13%). Herpes simplex virus (HSV) was the most common cause of encephalitis (18%); tick-borne encephalitis virus (TBEV) was the most common cause of nonbacterial meningoencephalitis (46%), enterovirus was the most common cause of nonbacterial meningitis (21%) and Streptococcus pneumoniae was the most common cause of bacterial meningoencephalitis/meningitis (49%). Overall, 35% patients remained without a known cause. After a median time of 16 months, 162 patients participated in the follow-up interview; 56% reported suffering from neurological long-term sequelae such as fatigue and/or excessive daytime sleepiness (34%), cognitive impairment and memory deficits (22%), headache (14%) and epileptic seizures (11%). CONCLUSIONS: In the Bern region, Switzerland, TBEV was the overall most frequently detected infectious cause, with a clinical manifestation of meningoencephalitis in the majority of cases. Long-term neurological sequelae, most importantly cognitive impairment, fatigue and headache, were frequently self-reported not only in encephalitis and meningoencephalitis survivors but also in viral meningitis survivors up to 40 months after acute infection.

Emergence of letermovir resistance in solid organ transplant recipients with ganciclovir resistant cytomegalovirus infection: A case series and review of the literature.

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.

SARS-CoV-2 Infection During Induction Chemotherapy in a Child With High-risk T-Cell Acute Lymphoblastic Leukemia.

The clinical course of SARS-CoV-2 infection (COVID-19) in children with hematologic malignancies is unclear. We describe the diagnosis, treatment and outcome of a 4-year-old boy with high-risk acute lymphoblastic leukemia and COVID-19. Regardless of immunosuppressive induction chemotherapy his symptoms remained moderate. He received only supportive treatment. Seroconversion occurred in a similar period as in immunocompetent adults. Despite prolonged myelosuppression he did neither acquire secondary infections nor did the treatment delay caused by the infection have a measurable negative impact on the residual disease of acute lymphoblastic leukemia. Intriguingly, residual leukemia even decreased even though he did not receive any antileukemic therapy.

A Sample-to-Report Solution for Taxonomic Identification of Cultured Bacteria in the Clinical Setting Based on Nanopore Sequencing.

Amplicon sequencing of the 16S rRNA gene is commonly used for the identification of bacterial isolates in diagnostic laboratories and mostly relies on the Sanger sequencing method. The latter, however, suffers from a number of limitations, with the most significant being the inability to resolve mixed amplicons when closely related species are coamplified from a mixed culture. This often leads to either increased turnaround time or absence of usable sequence data. Short-read next-generation sequencing (NGS) technologies could solve the mixed amplicon issue but would lack both cost efficiency at low throughput and fast turnaround times. Nanopore sequencing developed by Oxford Nanopore Technologies (ONT) could solve those issues by enabling a flexible number of samples per run and an adjustable sequencing time. Here, we report on the development of a standardized laboratory workflow combined with a fully automated analysis pipeline LORCAN (long read consensus analysis), which together provide a sample-to-report solution for amplicon sequencing and taxonomic identification of the resulting consensus sequences. Validation of the approach was conducted on a panel of reference strains and on clinical samples consisting of single or mixed rRNA amplicons associated with various bacterial genera by direct comparison to the corresponding Sanger sequences. Additionally, simulated read and amplicon mixtures were used to assess LORCAN's behavior when dealing with samples with known cross-contamination levels. We demonstrate that by combining ONT amplicon sequencing results with LORCAN, the accuracy of Sanger sequencing can be closely matched (>99.6% sequence identity) and that mixed samples can be resolved at the single-base resolution level. The presented approach has the potential to significantly improve the flexibility, reliability, and availability of amplicon sequencing in diagnostic settings.

Hantavirus Cardiopulmonary Syndrome Due to Imported Andes Hantavirus Infection in Switzerland: A Multidisciplinary Challenge, Two Cases and a Literature Review.

Two travellers returning from South America were diagnosed with Andes hantavirus infection, the only member of the Hantaviridae family known to be transmitted from person to person. We describe the clinical course and therapeutic and infection control measures. While both patients showed high viral load (VL) and shedding over several months, 1 patient recovered within 1 week from severe respiratory illness that required noninvasive ventilation, whereas the second patient developed severe hantavirus cardiopulmonary syndrome that required extracorporeal membrane oxygenation for 27 days. The clinical course in the latter patient was complicated by severe disseminated intravascular coagulopathy with diffuse hemorrhage that necessitated mass transfusions, as well as by multiple organ failure, including the need for renal replacement therapy. Results of VL in blood, respiratory secretions, and semen for the first 9 months of follow-up are reported. To our knowledge, these are the first cases of Andes hantavirus infection detected in Europe.

Impact of Tenofovir on Hepatitis Delta Virus Replication in the Swiss Human Immunodeficiency Virus Cohort Study.

We analyzed changes in hepatitis B virus and hepatitis delta virus (HDV) viral loads (VL) during tenofovir-containing antiretroviral therapy among patients with a replicating HDV infection in the Swiss HIV Cohort Study. Only 28.6% experienced a ≥2.0 log reduction in HDV RNA, and 14.3% had undetectable HDV VL within 5 years.

Hepatitis delta-associated mortality in HIV/HBV-coinfected patients.

BACKGROUND & AIMS: Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. We assessed the epidemiological characteristics of HDV infection in the nationwide Swiss HIV Cohort Study and evaluated its impact on clinical outcomes. METHODS: All HIV-infected patients with a positive hepatitis B surface antigen test were considered and tested for anti-HDV antibodies. HDV amplification and sequencing were performed in anti-HDV-positive patients. Demographic and clinical characteristics at initiation of antiretroviral therapy, as well as causes of death were compared between HDV-positive and HDV-negative individuals using descriptive statistics. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate the association between HDV infection and overall mortality, liver-related mortality as well as incidence of hepatocellular carcinoma (HCC). RESULTS: Of 818 patients with a positive hepatitis B surface antigen tests, 771 (94%) had a stored serum sample available and were included. The prevalence of HDV infection was 15.4% (119/771, 95% CI: 12.9-18.0) and the proportion of HDV-positive patients with HDV replication 62.9% (73/116). HDV-infected patients were more likely to be persons who inject drugs (60.6% vs. 9.1%) and to have a positive hepatitis C virus (HCV) serology (73.1% vs. 17.8%) compared to HDV-uninfected ones. HDV infection was strongly associated with overall death (adjusted hazard ratio 2.33, 95% CI 1.41-3.84), liver-related death (7.71, 3.13-18.97) and with the occurrence of HCC (9.30, 3.03-28.61). Results were similar when persons who inject drugs or HCV-coinfected patients were excluded from the analyses. CONCLUSIONS: The prevalence of HDV in hepatitis B surface antigen-positive patients in the Swiss HIV Cohort Study (SHCS) is high and HDV infection is independently associated with mortality and liver-related events, including HCC. LAY SUMMARY: Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. In a nationwide cohort of HIV-infected individuals in Switzerland, 15% of HBV-coinfected patients had antibodies to HDV infection, of which a majority had active HDV replication. HDV-infected individuals were 2.5 times more likely to die, eight times more likely to die from a liver-related cause and nine times more likely to develop liver cancer compared to HDV-uninfected ones. Our results emphasize the need for prevention programs (including HBV vaccination), the systematic screening of at risk populations as well as close monitoring, and underline the importance of developing new treatments for chronic HDV infection.

Do all Emergency Room Patients With Influenza-like Symptoms Need Blood Cultures? A Retrospective Cohort Study of 2 Annual Influenza Seasons.

In this retrospective cohort study, we evaluated risk factors for bacteremia in emergency department patients presenting with influenza-like symptoms during influenza epidemic seasons. In patients without fever, chronic heart or chronic liver disease, blood culture collection might be omitted.

Determination of the Diagnostic Performance of Laboratory Tests in the Absence of a Perfect Reference Standard: The Case of SARS-CoV-2 Tests.

BACKGROUND: Currently, assessing the diagnostic performance of new laboratory tests assumes a perfect reference standard, which is rarely the case. Wrong classifications of the true disease status will inevitably lead to biased estimates of sensitivity and specificity. OBJECTIVES: Using Bayesian' latent class models (BLCMs), an approach that does not assume a perfect reference standard, we re-analyzed data of a large prospective observational study assessing the diagnostic accuracy of an antigen test for the diagnosis of SARS-CoV-2 infection in clinical practice. METHODS: A cohort of consecutive patients presenting to a COVID-19 testing facility affiliated with a Swiss University Hospital were recruited (n = 1465). Two real-time PCR tests were conducted in parallel with the Roche/SD Biosensor rapid antigen test on nasopharyngeal swabs. A two-test (PCR and antigen test), three-population BLCM was fitted to the frequencies of paired test results. RESULTS: Based on the BLCM, the sensitivities of the RT-PCR and the Roche/SD Biosensor rapid antigen test were 98.5% [95% CRI 94.8;100] and 82.7% [95% CRI 66.8;100]. The specificities were 97.7% [96.1;99.7] and 99.9% [95% CRI 99.6;100]. CONCLUSIONS: Applying the BLCM, the diagnostic accuracy of RT-PCR was high but not perfect. In contrast to previous results, the sensitivity of the antigen test was higher. Our results suggest that BLCMs are valuable tools for investigating the diagnostic performance of laboratory tests in the absence of perfect reference standard.

Evolution of humoral immune response to SARS-CoV-2 mRNA vaccine in liver transplant recipients - a longitudinal study.

BACKGROUND AND AIM: 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. METHODS: 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". RESULTS: 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). DISCUSSION: 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.

Diagnostic accuracy of SARS-CoV-2 saliva antigen testing in a real-life clinical setting.

BACKGROUND: SARS-CoV-2 antigen tests with saliva facilitate examination in settings that lack trained personnel. However, little is known about the diagnostic accuracy in real-life clinical settings. Therefore, we studied the diagnostic accuracy of a saliva antigen test in diagnosing SARS-CoV-2 infection in a primary/secondary care testing facility. METHODS: Individuals who presented at a COVID-19 testing facility affiliated with a Swiss university hospital were prospectively recruited (n=377). Saliva specimen was obtained, and the PCL Inc. COVID19 Gold antigen test was conducted in parallel with 2 real-time polymerase chain reaction (RT-PCR) assays from a nasopharyngeal swab. RESULTS: RT-PCR results were positive in 53 individuals, corresponding to a prevalence of 14.1% (missing material in 1 individual). The PCL saliva antigen test was positive in 22 individuals (5.8%) and negative in 354 (93.9%). The sensitivity of the saliva antigen test was 30.2% (95% confidence interval 18.3, 44.3), both overall and in symptomatic individuals. The specificity was 98.1% (96.0, 99.3). CONCLUSIONS: The diagnostic accuracy of a SARS-CoV-2 saliva antigen test in a primary/secondary care testing facility was remarkably lower than that reported in the manufacturer's specifications.

Evaluation of the DiaSorin LIAISON SARS-CoV-2 antigen assay on nasopharyngeal swabs in two different SARS-CoV-2 pandemic waves in Switzerland: The impact of the Omicron variant on its performance.

Background: SARS-CoV-2 antigen tests reliably detect individuals with high viral loads and provide an efficient diagnostic tool to manage the current SARS-CoV-2 pandemic. However, mutations in SARS-CoV-2 variants of concerns that appeared after validation of most antigen tests might impact their diagnostic performance. Objectives: To assess the impact of the Omicron variant on the performance of the DiaSorin LIAISON SARS-CoV-2 antigen test, we evaluated its sensitivity and specificity on nasopharyngeal swabs (NPS) compared to rRT-PCR in the second and the Omicron pandemic wave in Switzerland. Study design: A random selection of NPS from patients undergoing SARS-CoV-2 diagnostics by rRT-PCR were collected during the second and the Omicron pandemic wave and further analyzed by the LIAISON antigen test. Sensitivity and specificity compared to rRT-PCR were calculated. Results: Test performance did not change in the two investigated periods. The overall sensitivity of 75.8% in the second and 76.5% in the Omicron wave increased to 87.1% and 88.4%, excluding samples with rRT-PCR Ct-value >30. By lowering the cut-off from 200 TCID50/ml to 62 TCID50/ml to discriminate between negative and positive samples using a ROC-curve, the sensitivity resulted in 88.8% for the second and 93.3% for the Omicron pandemic wave. The specificity of the LIAISON antigen test was 100% in both collectives. Conclusion: Omicron variant does not seem to affect the performance of the LIAISON antigen test. The WHO recommended sensitivity of ≥80% for antigen testing was fulfilled during both pandemic periods in samples with Ct-value <30 or by optimizing the assay cut-off.