Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy.

BACKGROUND: The majority of patients with B-cell-depleting therapies show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 immune responses in patients of the RituxiVac study compared with healthy volunteers and investigate the immunogenicity of a third vaccination in previously humoral non-responding patients. METHODS: We investigated the humoral and cell-mediated immune response after SARS-CoV-2 messanger RNA vaccination in patients with a history with anti-CD20 therapies. Coprimary outcomes were antispike and SARS-CoV-2-stimulated interferon-γ concentrations in vaccine responders 4.3 months (median; IQR: 3.6-4.8 months) after first evaluation, and humoral and cell-mediated immunity (CMI) after a third vaccine dose in previous humoral non-responders. Immunity decay rates were compared using analysis of covariance in linear regression. RESULTS: 5.6 months (IQR: 5.1-6.7) after the second vaccination, we detected antispike IgG in 88% (29/33) and CMI in 44% (14/32) of patients with a humoral response after two-dose vaccination compared with 92% (24/26) healthy volunteers with antispike IgG and 69% (11/16) with CMI 6.8 months after the second vaccination (IQR: 6.0-7.1). Decay rates of antibody concentrations were comparable between patients and controls (p=0.70). In two-dose non-responders, a third SARS-CoV-2 vaccine elicited humoral responses in 19% (6/32) and CMI in 32% (10/31) participants. CONCLUSION: This study reveals comparable immunity decay rates between patients with anti-CD20 treatments and healthy volunteers, but inefficient humoral or CMI after a third SARS-CoV-2 vaccine in most two-dose humoral non-responders calling for individually tailored vaccination strategies in this population.Trial registration numberNCT04877496; ClinicalTrials.gov number.

Humoral response to mRNA vaccines against SARS-CoV-2 in patients with humoral immunodeficiency disease.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

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.

Comparison of mRNA Vaccinations with BNT162b2 or mRNA-1273 in Anti-CD20-Treated Multiple Sclerosis Patients.

Objective: Anti-CD20-treated patients are at risk of a reduced humoral immune response during the SARS-CoV-2 pandemic. Our aim was to compare the antibody response after two vaccinations with the mRNA vaccines BNT162b2 or mRNA-1273 in patients with multiple sclerosis. Methods: Data from the University Hospital of Bern and Cantonal Hospital of Lucerne were retrospectively collected from medical records and then analyzed. Anti-spike IgG serum titers were collected from both centers and were considered to be protective from a value of ≥100 AU/mL. Continuous variables were given as the mean and 95% confidence interval (95% CI); categorical variables were given as frequencies. A Mann-Whitney test and Fisher's exact test as well as a multivariable linear regression analysis with anti-spike IgG (AU/mL) as the dependent variable were run using SPSS Statistic 25 (IBM Corp., Amonk, NY, USA). Results: A total of 74 patients were included; 41/74 (63.51%) were female patients and the mean age was 46.6 years (95% CI 43.4-49.9). Of these patients, 36/74 were vaccinated with BNT162b2 and 38/74 with mRNA-1273, following the national vaccination recommendation. In both vaccine groups, protective anti-spike IgG titers (≥100 AU/mL) were infrequently achieved (5/74: mRNA-1273 3/38; BNT162b2 2/36). Conclusions: In addition to a low rate of protective anti-spike IgG titers in both vaccine groups, we identified a drop in anti-spike IgG serum titers over time. This observation bears therapeutic consequences, as initial positive titers should be checked in case of an infection with the SARS-CoV-2 virus to identify patients who would benefit from an intravenous anti-spike IgG treatment against acute COVID-19.

Neuro-axonal injury in COVID-19: the role of systemic inflammation and SARS-CoV-2 specific immune response.

Background: In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune response with regard to neuronal injury has not yet been investigated. Methods: In a prospective cohort study, we recruited patients with mild-moderate (n = 39) and severe (n = 14) COVID-19 and measured sNfL levels, cytokine concentrations, SARS-CoV-2-specific antibodies including neutralizing antibody titers, and cell-mediated immune responses at enrollment and at 28(±7) days. We explored the association of neuro-axonal injury as by the means of sNfL measurements with disease severity, cytokine levels, and virus-specific immune responses. Results: sNfL levels, as an indicator for neuronal injury, were higher at enrollment and increased during follow-up in severely ill patients, whereas during mild-moderate COVID-19, sNfL levels remained unchanged. Severe COVID-19 was associated with increased concentrations of cytokines assessed [interleukin (IL)-6, IL-8, interleukin-1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α)], higher anti-spike IgG and anti-nucleocapsid IgG concentrations, and increased neutralizing antibody titers compared with mild-moderate disease. Patients with more severe disease had higher counts of defined SARS-CoV-2-specific T cells. Increases in sNfL concentrations from baseline to day 28(±7) positively correlated with anti-spike protein IgG antibody levels and with titers of neutralizing antibodies. Conclusion: Severe COVID-19 is associated with increased serum concentration of cytokines and subsequent neuronal injury as reflected by increased levels of sNfL. Patients with more severe disease developed higher neutralizing antibody titers and higher counts of SARS-CoV-2-specific T cells during the course of COVID-19 disease. Mounting a pronounced virus-specific humoral and cell-mediated immune response upon SARS-CoV-2 infection did not protect from neuro-axonal damage as by the means of sNfL levels.

Neuro-axonal injury in COVID-19: the role of systemic inflammation and SARS-CoV-2 specific immune response

Background: In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific immune response with regard to neuronal injury has not yet been investigated. Methods: In a prospective cohort study, we recruited patients with mild–moderate (n = 39) and severe (n = 14) COVID-19 and measured sNfL levels, cytokine concentrations, SARS-CoV-2-specific antibodies including neutralizing antibody titers, and cell-mediated immune responses at enrollment and at 28(±7) days. We explored the association of neuro-axonal injury as by the means of sNfL measurements with disease severity, cytokine levels, and virus-specific immune responses. Results: sNfL levels, as an indicator for neuronal injury, were higher at enrollment and increased during follow-up in severely ill patients, whereas during mild–moderate COVID-19, sNfL levels remained unchanged. Severe COVID-19 was associated with increased concentrations of cytokines assessed [interleukin (IL)-6, IL-8, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α)], higher anti-spike IgG and anti-nucleocapsid IgG concentrations, and increased neutralizing antibody titers compared with mild–moderate disease. Patients with more severe disease had higher counts of defined SARS-CoV-2-specific T cells. Increases in sNfL concentrations from baseline to day 28(±7) positively correlated with anti-spike protein IgG antibody levels and with titers of neutralizing antibodies. Conclusion: Severe COVID-19 is associated with increased serum concentration of cytokines and subsequent neuronal injury as reflected by increased levels of sNfL. Patients with more severe disease developed higher neutralizing antibody titers and higher counts of SARS-CoV-2-specific T cells during the course of COVID-19 disease. Mounting a pronounced virus-specific humoral and cell-mediated immune response upon SARS-CoV-2 infection did not protect from neuro-axonal damage as by the means of sNfL levels.

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.

Humoral and cellular responses to mRNA vaccines against SARS-CoV-2 in patients with a history of CD20 B-cell-depleting therapy (RituxiVac): an investigator-initiated, single-centre, open-label study.

BACKGROUND: B-cell-depleting therapies increase the risk of morbidity and mortality due to COVID-19. Evidence-based SARS-CoV-2 vaccination strategies for patients on B-cell-depleting therapies are scarce. We aimed to investigate humoral and cell-mediated immune responses to SARS-CoV-2 mRNA-based vaccines in patients receiving CD20-targeted B-cell-depleting agents for autoimmune disease, malignancy, or transplantation. METHODS: The RituxiVac study was an investigator-initiated, single-centre, open-label study done at the Bern University Hospital (Bern, Switzerland). Patients with a treatment history of anti-CD20-depleting agents (rituximab or ocrelizumab) and with no previous history of SARS-CoV-2 infection were enrolled between April 26 and June 30, 2021, for analysis of humoral and cell-mediated immune responses (by interferon-γ [IFNγ] release assay) at least 4 weeks after completing vaccination against SARS-CoV-2. Healthy controls without a history of SARS-CoV-2 infection were also enrolled at least 4 weeks after completing vaccination against SARS-CoV-2. All study participants received two doses of either the Pfizer-BioNTech BNT162b2 vaccine or the Moderna mRNA-1273 vaccine. The primary outcome was the proportion of patients with a history of anti-CD20 treatment who showed a humoral immune response against the SARS-CoV-2 spike protein in comparison with immunocompetent controls. Prespecified secondary endpoints were the effect of anti-CD20 therapy (including time since last treatment and cumulative dose) on humoral or cell-mediated immune responses to SARS-CoV-2 vaccination, and biomarkers of immunocompetence. This study is registered with ClinicalTrials.gov, NCT04877496. FINDINGS: The final study population comprised 96 patients and 29 immunocompetent controls. The median age of patients was 67 years (IQR 57-72) and of controls was 54 years (45-62), and 51 (53%) of 96 patients and 19 (66%) of 29 controls were female. The median time since last anti-CD20 treatment was 1·07 years (IQR 0·48-2·55) and the median cumulative dose of an anti-CD20 depleting agent was 2·80 g (1·50-5·00). Anti-spike IgG antibodies were detected in 47 (49%) of 96 patients 1·79 months (IQR 1·16-2·48) after the second vaccine dose compared to 29 (100%) of 29 controls 1·81 months (1·17-2·48) after the second vaccine dose (p<0·001). SARS-CoV-2-specific IFNγ release was detected in 13 (20%) of 66 patients and 21 (75%) of 28 of healthy controls (p<0·001). Only nine (14%) of 66 patients were double positive for anti-SARS-CoV-2 spike IgG and cell-mediated responses, compared with 21 (75%) of 28 healthy controls (p<0·001). Time since last anti-CD20 therapy (>7·6 months; positive predictive value 0·78), peripheral CD19+ cell count (>27 cells per µL; positive predictive value 0·70), and CD4+ lymphocyte count (>653 cells per µL; positive predictive value 0·71) were predictive of humoral vaccine response (area under the curve [AUC] 67% [95% CI 56-78] for time since last anti-CD20 therapy, 67% [55-80] for peripheral CD19+ count, and 66% [54-79] for CD4+ count). INTERPRETATION: This study provides further evidence of blunted humoral and cell-mediated immune responses elicited by SARS-CoV-2 mRNA vaccines in patients with a history of CD20 B-cell-depleting treatment. Lymphocyte subpopulation counts were associated with vaccine response in this highly vulnerable population. On validation, these results could help guide both the administration of SARS-CoV-2 vaccines and B-cell-depleting agents in this population. FUNDING: Bern University Hospital.

Seroprevalence of SARS-CoV-2 in healthcare workers from outpatient facilities and retirement or nursing homes in a Swiss canton.

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.

Diagnostic accuracy of a SARS-CoV-2 rapid antigen test in real-life clinical settings.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Evaluation of the Roche antigen rapid test and a cell culture-based assay compared to rRT- PCR for the detection of SARS-CoV-2: A contribution to the discussion about SARS-CoV-2 diagnostic tests and contagiousness.

Background: The most sensitive method to detect SARS-CoV-2 relies on rRT-PCR; however, viral RNA can be detected weeks/months after clinical resolution. Since rRT-PCR cannot discern between non- and infectious virus, it is unclear whether the presence of viral RNA after recovery reflects infectious SARS-CoV-2. However, recent studies suggest a positive correlation between antigen rapid tests (Ag-RDT) and virus isolation that is more suited to assess contagiousness. Objectives: To assess the utility of SARS-CoV-2 diagnostic tests in different settings we evaluated the performance of Ag-RDT-based and a cell culture-based SARS-CoV-2 assay in comparison to rRT-PCR. Study design: A total of 61 Nasopharyngeal-Swabs tested positive by cobasⓇ SARS-CoV-2 rRT-PCR were in parallel evaluated with the Roche Ag-RDT and a cell culture-based assay to detect SARS-CoV-2. Results: SARS-CoV-2 was successfully isolated in 51/61 samples corresponding to 83.6%, which was 97.3% or 96.2% when considering samples with E-gene Ct-value <25 and <28, respectively. In comparison, the Ag-RDT showed an overall sensitivity of 85.2%, that increased to 100% and 96.2% using an E-gene Ct-value cut-off of <25 and <28, respectively. There was an overall good agreement between the commercial Ag-RDT and our in-house cell culture-based SARS-CoV-2 detection assay. However, SARS-CoV-2 could be isolated from two samples that tested negative by Ag-RDT. Conclusions: Our results support the use of the Roche Ag-RDT to detect SARS-CoV-2 exposure in large scale populations. However, it is recommended to use rRT-PCR, potentially in conjunction with cell culture-based SARS-CoV-2 assay, to support clinicians in making decisions regarding fragile patient groups.

SARS-CoV-2 N501Y Introductions and Transmissions in Switzerland from Beginning of October 2020 to February 2021-Implementation of Swiss-Wide Diagnostic Screening and Whole Genome Sequencing.

The rapid spread of the SARS-CoV-2 lineages B.1.1.7 (N501Y.V1) throughout the UK, B.1.351 (N501Y.V2) in South Africa, and P.1 (B.1.1.28.1; N501Y.V3) in Brazil has led to the definition of variants of concern (VoCs) and recommendations for lineage specific surveillance. In Switzerland, during the last weeks of December 2020, we established a nationwide screening protocol across multiple laboratories, focusing first on epidemiological and microbiological definitions. In January 2021, we validated and implemented an N501Y-specific PCR to rapidly screen for VoCs, which are then confirmed using amplicon sequencing or whole genome sequencing (WGS). A total of 13,387 VoCs have been identified since the detection of the first Swiss case in October 2020, with 4194 being B.1.1.7, 172 B.1.351, and 7 P.1. The remaining 9014 cases of VoCs have been described without further lineage specification. Overall, all diagnostic centers reported a rapid increase of the percentage of detected VOCs, with a range of 6 to 46% between 25 to 31 of January 2021 increasing towards 41 to 82% between 22 to 28 of February. A total of 739 N501Y positive genomes were analysed and show a broad range of introduction events to Switzerland. In this paper, we describe the nationwide coordination and implementation process across laboratories, public health institutions, and researchers, the first results of our N501Y-specific variant screening, and the phylogenetic analysis of all available WGS data in Switzerland, that together identified the early introduction events and subsequent community spreading of the VoCs.

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.