Tafasitamab for patients with relapsed or refractory diffuse large B-cell lymphoma: final 5-year efficacy and safety findings in the phase II L-MIND study.

Tafasitamab, an anti-CD19 immunotherapy, is used with lenalidomide for patients with autologous stem cell transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma based on the results of the phase II L-MIND study (NCT02399085). We report the final 5-year analysis of this study. Eighty patients ≥18 years who had received one to three prior systemic therapies, and had Eastern Cooperative Oncology Group performance status 0-2 received up to 12 cycles of co-administered tafasitamab and lenalidomide, followed by tafasitamab monotherapy until disease progression or unacceptable toxicity. The primary endpoint was the best objective response rate. Secondary endpoints included duration of response, progression-free survival, overall survival, and safety. Exploratory analyses evaluated efficacy endpoints by prior lines of therapy. At data cutoff on November 14, 2022, the objective response rate was 57.5%, with a complete response rate of 41.3% (n=33), which was consistent with prior analyses. With a median follow-up of 44.0 months, the median duration of response was not reached. The median progression-free survival was 11.6 months (95% confidence interval [95% CI]: 5.7-45.7) with a median follow-up of 45.6 months. The median overall survival was 33.5 months (95% CI: 18.3-not reached) with a median follow-up of 65.6 months. Patients who had received one prior line of therapy (n=40) showed a higher objective response rate (67.5%; 52.5% complete responses) compared to patients who had received two or more prior lines of therapy (n=40; 47.5%; 30% complete responses), but the median duration of response was not reached in either subgroup. Other exploratory analyses revealed consistent long-term efficacy results across subgroups. Adverse events were consistent with those described in previous reports, were manageable, and their frequency decreased during tafasitamab monotherapy, with no new safety concerns. This final 5-year analysis of L-MIND demonstrates that the immunotherapy combination of tafasitamab and lenalidomide is well tolerated and has long-term clinical benefit with durable responses.

Studying temporal titre evolution of commercial SARS-CoV-2 assays reveals significant shortcomings of using BAU standardization for comparison.

BACKGROUND: Measuring specific anti-SARS-CoV-2 antibodies has become one of the main epidemiological tools to survey the ongoing SARS-CoV-2 pandemic, but also vaccination response. The WHO made available a set of well-characterized samples derived from recovered individuals to allow normalization between different quantitative anti-Spike assays to defined Binding Antibody Units (BAU). METHODS: To assess sero-responses longitudinally, a cohort of ninety-nine SARS-CoV-2 RT-PCR positive subjects was followed up together with forty-five vaccinees without previous infection but with two vaccinations. Sero-responses were evaluated using a total of six different assays: four measuring anti-Spike proteins (converted to BAU), one measuring anti-Nucleocapsid proteins and one SARS-CoV-2 surrogate virus neutralization. Both cohorts were evaluated using the Euroimmun Anti-SARS-CoV-2-ELISA anti-S1 IgG and the Roche Elecsys Anti-SARS-CoV-2 anti-S1 assay. RESULTS: In SARS-CoV-2-convalesce subjects, the BAU-sero-responses of Euroimmun Anti-SARS-CoV-2-ELISA anti-S1 IgG and Roche Elecsys Anti-SARS-CoV-2 anti-S1 peaked both at 47 (43-51) days, the first assay followed by a slow decay thereafter (> 208 days), while the second assay not presenting any decay within one year. Both assay values in BAUs are only equivalent a few months after infection, elsewhere correction factors up to 10 are necessary. In contrast, in infection-naive vaccinees the assays perform similarly. CONCLUSION: The results of our study suggest that the establishment of a protective correlate or vaccination booster recommendation based on different assays, although BAU-standardised, is still challenging. At the moment the characteristics of the available assays used are not related, and the BAU-standardisation is unable to correct for that.

The representative COVID-19 cohort Munich (KoCo19): from the beginning of the pandemic to the Delta virus variant.

BACKGROUND: Population-based serological studies allow to estimate prevalence of SARS-CoV-2 infections despite a substantial number of mild or asymptomatic disease courses. This became even more relevant for decision making after vaccination started. The KoCo19 cohort tracks the pandemic progress in the Munich general population for over two years, setting it apart in Europe. METHODS: Recruitment occurred during the initial pandemic wave, including 5313 participants above 13 years from private households in Munich. Four follow-ups were held at crucial times of the pandemic, with response rates of at least 70%. Participants filled questionnaires on socio-demographics and potential risk factors of infection. From Follow-up 2, information on SARS-CoV-2 vaccination was added. SARS-CoV-2 antibody status was measured using the Roche Elecsys® Anti-SARS-CoV-2 anti-N assay (indicating previous infection) and the Roche Elecsys® Anti-SARS-CoV-2 anti-S assay (indicating previous infection and/or vaccination). This allowed us to distinguish between sources of acquired antibodies. RESULTS: The SARS-CoV-2 estimated cumulative sero-prevalence increased from 1.6% (1.1-2.1%) in May 2020 to 14.5% (12.7-16.2%) in November 2021. Underreporting with respect to official numbers fluctuated with testing policies and capacities, becoming a factor of more than two during the second half of 2021. Simultaneously, the vaccination campaign against the SARS-CoV-2 virus increased the percentage of the Munich population having antibodies, with 86.8% (85.5-87.9%) having developed anti-S and/or anti-N in November 2021. Incidence rates for infections after (BTI) and without previous vaccination (INS) differed (ratio INS/BTI of 2.1, 0.7-3.6). However, the prevalence of infections was higher in the non-vaccinated population than in the vaccinated one. Considering the whole follow-up time, being born outside Germany, working in a high-risk job and living area per inhabitant were identified as risk factors for infection, while other socio-demographic and health-related variables were not. Although we obtained significant within-household clustering of SARS-CoV-2 cases, no further geospatial clustering was found. CONCLUSIONS: Vaccination increased the coverage of the Munich population presenting SARS-CoV-2 antibodies, but breakthrough infections contribute to community spread. As underreporting stays relevant over time, infections can go undetected, so non-pharmaceutical measures are crucial, particularly for highly contagious strains like Omicron.

Tuberculosis Molecular Bacterial Load Assay Reveals Early Delayed Bacterial Killing in Patients With Relapse.

Bacterial killing in patients with tuberculosis (TB) relapse was compared to that in patients achieving cure, measured by TB molecular bacterial load assay (TB-MBLA) or mycobacteria growth indicator tube (MGIT) time to positivity (TTP). TB-MBLA in 4 relapsed patients was significantly different compared to 132 cured patients after 2 weeks of treatment; MGIT TTP showed a significant difference from week 8.

Tuberculosis and Sexual and Reproductive Health of Women in Four African Countries.

Tuberculosis (TB) is a major reason of maternal mortality in low-income countries, and it increases the probability of adverse sexual and reproductive health (SRH) outcomes, including ectopic pregnancy and perinatal mortality. The data presented here is from the TB Sequel observational cohort conducted in four African countries. For this sub-study, we selected only female participants, who were diagnosed with drug susceptible TB and followed-up until the end of anti-TB treatment. The data collection included questionnaires, clinical examination and laboratory tests at TB diagnosis, day 14, month 2, 4 and 6. A total of 486 women, with 88.3% being 18-49 years old, were included in the analysis. Around 54.7% were HIV positive. Most of the participants (416/486; 85.6%) in our cohort were considered cured at month 6. Only 40.4% of non-pregnant women of reproductive age used contraception at TB diagnosis. A total of 31 out of 486 women experienced pregnancy during TB treatment. Pregnancy outcomes varied between live birth (16/31; 51.6%), induced abortion (6/31; 19.4%), miscarriage (4/31; 12.9%) and stillbirth (3/31; 9.6%). Integration and linking of SRH services with TB programmes are vital to increase contraception use and protect women from obstetric risks associated with pregnancy during TB treatment.

Tuberculosis Treatment Response Monitoring by the Phenotypic Characterization of MTB-Specific CD4+ T-Cells in Relation to HIV Infection Status.

HIV infection causes systemic immune activation, impacts TB disease progression and hence may influence the diagnostic usability of Mycobacterium tuberculosis-specific T cell profiling. We investigated changes of activation and maturation markers on MTB-specific CD4+ T-cells after anti-tuberculosis treatment initiation in relation to HIV status and the severity of lung impairment. Thawed peripheral blood mononuclear cells from TB patients with (n = 27) and without HIV (n = 17) were analyzed using an intracellular IFN-γ assay and flow cytometry 2 and 6 months post-TB treatment initiation. H37Rv antigen was superior to the profile MTB-specific CD4+ T-cells phenotype when compared to PPD and ESAT6/CFP10. Regardless of HIV status and the severity of lung impairment, activation markers (CD38, HLA-DR and Ki67) on MTB-specific CD4+ T-cells declined after TB treatment initiation (p < 0.01), but the expression of the maturation marker CD27 did not change over the course of TB treatment. The MTB-specific T cell phenotype before, during and after treatment completion was similar between people living with and without HIV, as well as between subjects with severe and mild lung impairment. These data suggest that the assessment of activation and maturation markers on MTB-specific CD4+ T-cells can be useful for TB treatment monitoring, regardless of HIV status and the severity of lung disease.

Health-related quality of life and psychological distress among adults in Tanzania: a cross-sectional study.

BACKGROUND: Little data is available on health-related quality of life (HRQoL) and mental health of the general population in Tanzania. We aimed to describe HRQoL and level of psychological distress among adults in Mbeya and Songwe Regions of Tanzania. METHODS: We conducted a cross-sectional study between April and October 2019 in Mbeya and Songwe Regions. Data were collected using the Medical Outcomes Short Form-36 (SF-36) questionnaire and the Page Kessler Psychological Distress Scale (K10). We described demographic characteristics of participants and used log-binomial regression to identify participant characteristics associated with psychological distress (K10 score ≥ 20). RESULTS: A total of 393 adults were enrolled. The participants had a median age of 29 years (IQR 23-40) and 54.2% were male. Participants reported a physical component summary score (PCS) with a mean of 54.7 (SD7.1) and a mental component summary score (MCS) with a mean of 55.5 (SD5.1). Older participants (≥ 40 year) and those that were divorced/widowed reported lower physical functioning, energy/vitality and emotional well-being compared to their counterparts (p < 0.05). In terms of psychological distress, majority of participants (78.4%; 305/389) reported that they were likely to be well (K10 score < 20), while 13.4% (52/389) reported to have mild (K10 score 20-24), 5.7% (22/389) moderate (K10 score 25-29), and 2.6% (10/389) severe (K10 score ≥ 30) psychological distress. CONCLUSIONS: Physical function and mental well-being in this adult population from Tanzania were lower than that reported in other similar research in Tanzania and other African countries. This study provides valuable references for other research initiatives and clinical services in this region.

The interplay of viral loads, clinical presentation, and serological responses in SARS-CoV-2 - Results from a prospective cohort of outpatient COVID-19 cases.

Risk factors for disease progression and severity of SARS-CoV-2 infections require an understanding of acute and long-term virological and immunological dynamics. Fifty-one RT-PCR positive COVID-19 outpatients were recruited between May and December 2020 in Munich, Germany, and followed up at multiple defined timepoints for up to one year. RT-PCR and viral culture were performed and seroresponses measured. Participants were classified applying the WHO clinical progression scale. Short symptom to test time (median 5.0 days; p = 0.0016) and high viral loads (VL; median maximum VL: 3∙108 copies/mL; p = 0.0015) were indicative for viral culture positivity. Participants with WHO grade 3 at baseline had significantly higher VLs compared to those with WHO 1 and 2 (p = 0.01). VLs dropped fast within 1 week of symptom onset. Maximum VLs were positively correlated with the magnitude of Ro-N-Ig seroresponse (p = 0.022). Our results describe the dynamics of VLs and antibodies to SARS-CoV-2 in mild to moderate cases that can support public health measures during the ongoing global pandemic.

Neutrophils Contribute to Severity of Tuberculosis Pathology and Recovery From Lung Damage Pre- and Posttreatment.

BACKGROUND: Despite microbiological cure, about 50% of tuberculosis (TB) patients have poor lung recovery. Neutrophils are associated with lung pathology; however, CD16/CD62L-defined subsets have not been studied in TB. Using flow cytometry, we monitored frequencies, phenotype, and function of neutrophils following stimulation with Mycobacterium tuberculosis (Mtb) whole cell lysate (WCL) and ESAT-6/CFP-10 fusion protein (EC) in relation to lung pathology. METHODS: Fresh blood from 42 adult, human immunodeficiency virus (HIV)-negative TB patients were analyzed pre- and post-therapy, with disease severity determined using chest radiography and bacterial load. Flow cytometry was used to monitor frequencies, phenotype, and function (generation of reactive oxygen species [ROS], together with CD11b, tumor necrosis factor, and interleukin 10 [IL-10] expression) of neutrophils following 2-hour stimulation with Mtb-specific antigens. RESULTS: Total neutrophils decreased by post-treatment compared to baseline (P = .0059); however, CD16brCD62Lbr (segmented) neutrophils increased (P = .0031) and CD16dimCD62Lbr (banded) neutrophils decreased (P = .038). Banded neutrophils were lower in patients with severe lung damage at baseline (P = .035). Following WCL stimulation, ROS from segmented neutrophils was higher in patients with low Mtb loads even after adjusting for sex (P = .038), whereas IL-10-expressing CD16dimCD62Llo cells were higher in patients with mild damage (P = .0397) at baseline. CONCLUSIONS: High ROS generation, low levels of banded neutrophils, and high levels of IL-10-expressing CD16dimCD62Llo neutrophils are associated with reduced lung pathology at diagnosis. Hence, neutrophils are potential early indicators of TB severity and promising targets for TB host-directed therapy.

Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients.

Background: The inflammatory response to Mycobacterium tuberculosis results in variable degrees of lung pathology during active TB (ATB) with central involvement of neutrophils. Little is known about neutrophil-derived mediators and their role in disease severity at baseline and recovery upon TB treatment initiation. Methods: 107 adults with confirmed pulmonary TB were categorised based on lung pathology at baseline and following successful therapy using chest X-ray scores (Ralph scores) and GeneXpert bacterial load (Ct values). Plasma, sputum, and antigen-stimulated levels of MMP1, MMP3, MMP8, MMP9, MPO, S100A8/9, IL8, IL10, IL12/23(p40), GM-CSF, IFNγ, and TNF were analysed using multiplex cytokine arrays. Results: At baseline, neutrophil counts correlated with plasma levels of MMP8 (rho = 0.45, p = 2.80E-06), S100A8 (rho = 0.52, p = 3.00E-08) and GM-CSF (rho = 0.43, p = 7.90E-06). Levels of MMP8 (p = 3.00E-03), MMP1 (p = 1.40E-02), S100A8 (p = 1.80E-02) and IL12/23(p40) (p = 1.00E-02) were associated with severe lung damage, while sputum MPO levels were directly linked to lung damage (p = 1.80E-03), Mtb load (p = 2.10E-02) and lung recovery (p = 2.40E-02). Six months of TB therapy significantly decreased levels of major neutrophil-derived pro-inflammatory mediators: MMP1 (p = 4.90E-12 and p = 2.20E-07), MMP8 (p = 3.40E-14 and p = 1.30E-05) and MMP9 (p = 1.60E-04 and p = 1.50E-03) in plasma and sputum, respectively. Interestingly, following H37Rv whole cell lysate stimulation, S100A8 (p = 2.80E-02), MMP9 (p = 3.60E-02) and MPO (p = 9.10E-03) levels at month 6 were significantly higher compared to baseline. Sputum MMP1 (p = 1.50E-03), MMP3 (p = 7.58E-04), MMP9 (p = 2.60E-02) and TNF (p = 3.80E-02) levels were lower at month 6 compared to baseline in patients with good lung recovery. Conclusion: In this study, patients with severe lung pathology at baseline and persistent lung damage after treatment were associated with higher plasma and sputum levels of major pro-inflammatory neutrophil-derived mediators. Interestingly, low sputum MPO levels were associated with severe lung damage, higher Mtb burden and low recovery. Our data suggest that therapeutic agents which target these mediators should be considered for future studies on biomarkers and host-directed therapeutic approaches against TB-related lung pathology and/or lung recovery.

Seroepidemiology and model-based prediction of SARS-CoV-2 in Ethiopia: longitudinal cohort study among front-line hospital workers and communities.

BACKGROUND: Over 1 year since the first reported case, the true COVID-19 burden in Ethiopia remains unknown due to insufficient surveillance. We aimed to investigate the seroepidemiology of SARS-CoV-2 among front-line hospital workers and communities in Ethiopia. METHODS: We did a population-based, longitudinal cohort study at two tertiary teaching hospitals involving hospital workers, rural residents, and urban communities in Jimma and Addis Ababa. Hospital workers were recruited at both hospitals, and community participants were recruited by convenience sampling including urban metropolitan settings, urban and semi-urban settings, and rural communities. Participants were eligible if they were aged 18 years or older, had provided written informed consent, and were willing to provide blood samples by venepuncture. Only one participant per household was recruited. Serology was done with Elecsys anti-SARS-CoV-2 anti-nucleocapsid assay in three consecutive rounds, with a mean interval of 6 weeks between tests, to obtain seroprevalence and incidence estimates within the cohorts. FINDINGS: Between Aug 5, 2020, and April 10, 2021, we did three survey rounds with a total of 1104 hospital workers and 1229 community residents participating. SARS-CoV-2 seroprevalence among hospital workers increased strongly during the study period: in Addis Ababa, it increased from 10·9% (95% credible interval [CrI] 8·3-13·8) in August, 2020, to 53·7% (44·8-62·5) in February, 2021, with an incidence rate of 2223 per 100 000 person-weeks (95% CI 1785-2696); in Jimma Town, it increased from 30·8% (95% CrI 26·9-34·8) in November, 2020, to 56·1% (51·1-61·1) in February, 2021, with an incidence rate of 3810 per 100 000 person-weeks (95% CI 3149-4540). Among urban communities, an almost 40% increase in seroprevalence was observed in early 2021, with incidence rates of 1622 per 100 000 person-weeks (1004-2429) in Jimma Town and 4646 per 100 000 person-weeks (2797-7255) in Addis Ababa. Seroprevalence in rural communities increased from 18·0% (95% CrI 13·5-23·2) in November, 2020, to 31·0% (22·3-40·3) in March, 2021. INTERPRETATION: SARS-CoV-2 spread in Ethiopia has been highly dynamic among hospital worker and urban communities. We can speculate that the greatest wave of SARS-CoV-2 infections is currently evolving in rural Ethiopia, and thus requires focused attention regarding health-care burden and disease prevention. FUNDING: Bavarian State Ministry of Sciences, Research, and the Arts; Germany Ministry of Education and Research; EU Horizon 2020 programme; Deutsche Forschungsgemeinschaft; and Volkswagenstiftung.

Head-to-head evaluation of seven different seroassays including direct viral neutralisation in a representative cohort for SARS-CoV-2.

A number of seroassays are available for SARS-CoV-2 testing; yet, head-to-head evaluations of different testing principles are limited, especially using raw values rather than categorical data. In addition, identifying correlates of protection is of utmost importance, and comparisons of available testing systems with functional assays, such as direct viral neutralisation, are needed.We analysed 6658 samples consisting of true-positives (n=193), true-negatives (n=1091), and specimens of unknown status (n=5374). For primary testing, we used Euroimmun-Anti-SARS-CoV-2-ELISA-IgA/IgG and Roche-Elecsys-Anti-SARS-CoV-2. Subsequently virus-neutralisation, GeneScriptcPass, VIRAMED-SARS-CoV-2-ViraChip, and Mikrogen-recomLine-SARS-CoV-2-IgG were applied for confirmatory testing. Statistical modelling generated optimised assay cut-off thresholds. Sensitivity of Euroimmun-anti-S1-IgA was 64.8%, specificity 93.3% (manufacturer's cut-off); for Euroimmun-anti-S1-IgG, sensitivity was 77.2/79.8% (manufacturer's/optimised cut-offs), specificity 98.0/97.8%; Roche-anti-N sensitivity was 85.5/88.6%, specificity 99.8/99.7%. In true-positives, mean and median Euroimmun-anti-S1-IgA and -IgG titres decreased 30/90 days after RT-PCR-positivity, Roche-anti-N titres decreased significantly later. Virus-neutralisation was 80.6% sensitive, 100.0% specific (≥1:5 dilution). Neutralisation surrogate tests (GeneScriptcPass, Mikrogen-recomLine-RBD) were >94.9% sensitive and >98.1% specific. Optimised cut-offs improved test performances of several tests. Confirmatory testing with virus-neutralisation might be complemented with GeneScriptcPassTM or recomLine-RBD for certain applications. Head-to-head comparisons given here aim to contribute to the refinement of testing strategies for individual and public health use.

From first to second wave: follow-up of the prospective COVID-19 cohort (KoCo19) in Munich (Germany).

BACKGROUND: In the 2nd year of the COVID-19 pandemic, knowledge about the dynamics of the infection in the general population is still limited. Such information is essential for health planners, as many of those infected show no or only mild symptoms and thus, escape the surveillance system. We therefore aimed to describe the course of the pandemic in the Munich general population living in private households from April 2020 to January 2021. METHODS: The KoCo19 baseline study took place from April to June 2020 including 5313 participants (age 14 years and above). From November 2020 to January 2021, we could again measure SARS-CoV-2 antibody status in 4433 of the baseline participants (response 83%). Participants were offered a self-sampling kit to take a capillary blood sample (dry blood spot; DBS). Blood was analysed using the Elecsys® Anti-SARS-CoV-2 assay (Roche). Questionnaire information on socio-demographics and potential risk factors assessed at baseline was available for all participants. In addition, follow-up information on health-risk taking behaviour and number of personal contacts outside the household (N = 2768) as well as leisure time activities (N = 1263) were collected in summer 2020. RESULTS: Weighted and adjusted (for specificity and sensitivity) SARS-CoV-2 sero-prevalence at follow-up was 3.6% (95% CI 2.9-4.3%) as compared to 1.8% (95% CI 1.3-3.4%) at baseline. 91% of those tested positive at baseline were also antibody-positive at follow-up. While sero-prevalence increased from early November 2020 to January 2021, no indication of geospatial clustering across the city of Munich was found, although cases clustered within households. Taking baseline result and time to follow-up into account, men and participants in the age group 20-34 years were at the highest risk of sero-positivity. In the sensitivity analyses, differences in health-risk taking behaviour, number of personal contacts and leisure time activities partly explained these differences. CONCLUSION: The number of citizens in Munich with SARS-CoV-2 antibodies was still below 5% during the 2nd wave of the pandemic. Antibodies remained present in the majority of SARS-CoV-2 sero-positive baseline participants. Besides age and sex, potentially confounded by differences in behaviour, no major risk factors could be identified. Non-pharmaceutical public health measures are thus still important.

A dried blood spot protocol for high throughput analysis of SARS-CoV-2 serology based on the Roche Elecsys anti-N assay.

BACKGROUND: Since 2020 SARS-CoV-2 spreads pandemically, infecting more than 119 million people, causing >2·6 million fatalities. Symptoms of SARS-CoV-2 infection vary greatly, ranging from asymptomatic to fatal. Different populations react differently to the disease, making it very hard to track the spread of the infection in a population. Measuring specific anti-SARS-CoV-2 antibodies is an important tool to assess the spread of the infection or successful vaccinations. To achieve sufficient sample numbers, alternatives to venous blood sampling are needed not requiring medical personnel or cold-chains. Dried-blood-spots (DBS) on filter-cards have been used for different studies, but not routinely for serology. METHODS: We developed a semi-automated protocol using self-sampled DBS for SARS-CoV-2 serology. It was validated in a cohort of matched DBS and venous-blood samples (n = 1710). Feasibility is demonstrated with two large serosurveys with 10247 company employees and a population cohort of 4465 participants. FINDINGS: Sensitivity and specificity reached 99·20% and 98·65%, respectively. Providing written instructions and video tutorials, 99·87% (4465/4471) of the unsupervised home sampling DBS cards could be analysed. INTERPRETATION: DBS-sampling is a valid and highly reliable tool for large scale serosurveys. We demonstrate feasibility and accuracy with a large validation cohort including unsupervised home sampling. This protocol might be of big importance for surveillance in resource-limited settings, providing low-cost highly accurate serology data. FUNDING: Provided by Bavarian State Ministry of Science and the Arts, LMU University-Hospital; Helmholtz-Centre-Munich, German Ministry for Education and Research (project01KI20271); University of Bonn; University of Bielefeld; the Medical Biodefense Research Program of Bundeswehr-Medical-Service; Euroimmun, RocheDiagnostics provided discounted kits and machines.

In Search of the SARS-CoV-2 Protection Correlate: Head-to-Head Comparison of Two Quantitative S1 Assays in Pre-characterized Oligo-/Asymptomatic Patients.

BACKGROUND: Quantitative serological assays detecting response to SARS-CoV-2 are needed to quantify immunity. This study analyzed the performance and correlation of two quantitative anti-S1 assays in oligo-/asymptomatic individuals from a population-based cohort. METHODS: In total, 362 plasma samples (108 with reverse transcription-polymerase chain reaction [RT-PCR]-positive pharyngeal swabs, 111 negative controls, and 143 with positive serology without confirmation by RT-PCR) were tested with quantitative assays (Euroimmun Anti-SARS-CoV-2 QuantiVac enzyme-linked immunosorbent assay [EI-S1-IgG-quant]) and Roche Elecsys® Anti-SARS-CoV-2 S [Ro-RBD-Ig-quant]), which were compared with each other and confirmatory tests, including wild-type virus micro-neutralization (NT) and GenScript®cPass™. Square roots R of coefficients of determination were calculated for continuous variables and non-parametric tests were used for paired comparisons. RESULTS: Quantitative anti-S1 serology correlated well with each other (true positives, 96%; true negatives, 97%). Antibody titers decreased over time (< 30 to > 240 days after initial positive RT-PCR). Agreement with GenScript-cPass was 96%/99% for true positives and true negatives, respectively, for Ro-RBD-Ig-quant and 93%/97% for EI-S1-IgG-quant. Ro-RBD-Ig-quant allowed distinct separation between positives and negatives, and less non-specific reactivity versus EI-S1-IgG-quant. Raw values (95% CI) ≥ 28.7 U/mL (22.6-36.4) for Ro-RBD-Ig-quant and ≥ 49.8 U/mL (43.4-57.1) for EI-S1-IgG-quant predicted NT > 1:5 in 95% of cases. CONCLUSIONS: Our findings suggest both quantitative anti-S1 assays (EI-S1-IgG-quant and Ro-RBD-Ig-quant) may replace direct neutralization assays in quantitative measurement of immune protection against SARS-CoV-2 in certain circumstances. However, although the mean antibody titers for both assays tended to decrease over time, a higher proportion of Ro-RBD-Ig-quant values remained positive after 240 days.

In Search of the SARS-CoV-2 Protection Correlate: Head-to-Head Comparison of Two Quantitative S1 Assays in Pre-characterized Oligo-/Asymptomatic Patients.

BACKGROUND: Quantitative serological assays detecting response to SARS-CoV-2 are needed to quantify immunity. This study analyzed the performance and correlation of two quantitative anti-S1 assays in oligo-/asymptomatic individuals from a population-based cohort. METHODS: In total, 362 plasma samples (108 with reverse transcription-polymerase chain reaction [RT-PCR]-positive pharyngeal swabs, 111 negative controls, and 143 with positive serology without confirmation by RT-PCR) were tested with quantitative assays (Euroimmun Anti-SARS-CoV-2 QuantiVac enzyme-linked immunosorbent assay [EI-S1-IgG-quant]) and Roche Elecsys® Anti-SARS-CoV-2 S [Ro-RBD-Ig-quant]), which were compared with each other and confirmatory tests, including wild-type virus micro-neutralization (NT) and GenScript®cPass™. Square roots R of coefficients of determination were calculated for continuous variables and non-parametric tests were used for paired comparisons. RESULTS: Quantitative anti-S1 serology correlated well with each other (true positives, 96%; true negatives, 97%). Antibody titers decreased over time (< 30 to > 240 days after initial positive RT-PCR). Agreement with GenScript-cPass was 96%/99% for true positives and true negatives, respectively, for Ro-RBD-Ig-quant and 93%/97% for EI-S1-IgG-quant. Ro-RBD-Ig-quant allowed distinct separation between positives and negatives, and less non-specific reactivity versus EI-S1-IgG-quant. Raw values (95% CI) ≥ 28.7 U/mL (22.6-36.4) for Ro-RBD-Ig-quant and ≥ 49.8 U/mL (43.4-57.1) for EI-S1-IgG-quant predicted NT > 1:5 in 95% of cases. CONCLUSIONS: Our findings suggest both quantitative anti-S1 assays (EI-S1-IgG-quant and Ro-RBD-Ig-quant) may replace direct neutralization assays in quantitative measurement of immune protection against SARS-CoV-2 in certain circumstances. However, although the mean antibody titers for both assays tended to decrease over time, a higher proportion of Ro-RBD-Ig-quant values remained positive after 240 days. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40121-021-00475-x.

Prevalence and Risk Factors of Infection in the Representative COVID-19 Cohort Munich.

Given the large number of mild or asymptomatic SARS-CoV-2 cases, only population-based studies can provide reliable estimates of the magnitude of the pandemic. We therefore aimed to assess the sero-prevalence of SARS-CoV-2 in the Munich general population after the first wave of the pandemic. For this purpose, we drew a representative sample of 2994 private households and invited household members 14 years and older to complete questionnaires and to provide blood samples. SARS-CoV-2 seropositivity was defined as Roche N pan-Ig ≥ 0.4218. We adjusted the prevalence for the sampling design, sensitivity, and specificity. We investigated risk factors for SARS-CoV-2 seropositivity and geospatial transmission patterns by generalized linear mixed models and permutation tests. Seropositivity for SARS-CoV-2-specific antibodies was 1.82% (95% confidence interval (CI) 1.28-2.37%) as compared to 0.46% PCR-positive cases officially registered in Munich. Loss of the sense of smell or taste was associated with seropositivity (odds ratio (OR) 47.4; 95% CI 7.2-307.0) and infections clustered within households. By this first population-based study on SARS-CoV-2 prevalence in a large German municipality not affected by a superspreading event, we could show that at least one in four cases in private households was reported and known to the health authorities. These results will help authorities to estimate the true burden of disease in the population and to take evidence-based decisions on public health measures.

Describing nearly two decades of Chagas disease in Germany and the lessons learned: a retrospective study on screening, detection, diagnosis, and treatment of Trypanosoma cruzi infection from 2000 - 2018.

BACKGROUND: The highly complex and largely neglected Chagas disease (CD) has become a global health problem due to population movements between Latin America and non-endemic countries, as well as non-vectorial transmission routes. Data on CD testing and treatment from routine patient care in Germany of almost two decades was collected and analysed. METHODS: German laboratories offering diagnostics for chronic Trypanosoma cruzi (T. cruzi) infection in routine patient care were identified. All retrievable data on tests performed during the years of 2000-2018 were analysed. Additional clinical information regarding patients diagnosed with CD was collected through questionnaires. RESULTS: Five German laboratories with diagnostics for T. cruzi infection in routine patient care were identified. Centres in Hamburg and Munich offered two independent serological tests to confirm the CD diagnosis, as recommended by WHO during the entire time period 2000-2018. Overall, a total of n = 10,728 independent tests involving n = 5991 individuals were identified with a progressive increase in testing rates over time, only n = 130 (16.0%) of the tested individuals with known nationality came from CD endemic countries. Of all test units conducted at the included institutes, a total of n = 347/10,728 (3.2%) tests on CD were positive, of which n = 200/347 (57.6%) were ELISA, n = 133/347 (38.3%) IFT, n = 10/347 (2.9%) PCR, and n = 4/347 (1.2%) RDT. Of the n = 5991 individuals only n = 81 (1.4%) with chronic infection were identified, n = 52 females and n = 28 males. Additional clinical information could only be collected from n = 47. CONCLUSION: The results of this study give insight into the deployment of screening, detection, diagnosis, and treatment of T. cruzi over the last two decades in Germany and existing deficits therein; the creation of guidelines for Germany could be a step forward to improve the existing gaps.

Lung Function Testing and Prediction Equations in Adult Population from Maputo, Mozambique.

Background: Local spirometric prediction equations are of great importance for interpreting lung function results and deciding on the management strategies for respiratory patients, yet available data from African countries are scarce. The aim of this study was to collect lung function data using spirometry in healthy adults living in Maputo, Mozambique and to derive first spirometric prediction equations for this population. Methods: We applied a cross-sectional study design. Participants, who met the inclusion criteria, underwent a short interview, anthropometric measurements, and lung function testing. Different modelling approaches were followed for generating new, Mozambican, prediction equations and for comparison with the Global Lung Initiative (GLI) and South African equations. The pulmonary function performance of participants was assessed against the different reference standards. Results: A total of 212 males and females were recruited, from whom 155 usable spirometry results were obtained. The mean age of participants was 35.20 years (SD 10.99) and 93 of 155 (59.35%) were females. The predicted values for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and the FEV1/FVC ratio based on the Mozambican equations were lower than the South African-and the GLI-based predictions. Conclusions: This study provides first data on pulmonary function in healthy Mozambican adults and describes how they compare to GLI and South African reference values for spirometry.