Health-Related Quality of Life and Impact of Socioeconomic Status among Primary and Secondary School Students after the third COVID-19 Wave in Berlin, Germany (preprint)

In the earlier phases of the COVID-19 pandemic, studies in Germany and elsewhere found an overall reduction in health-related quality of life (HRQoL) among students. However, there is little evidence on later pandemic stages as well as socioeconomic influencing factors. We aimed to 1) describe HRQoL in a Berlin student cohort at two time points in mid-2021, and to 2) analyze the effects of household income and education. We assessed HRQoL of students from 24 randomly selected primary and secondary schools in Berlin, Germany with the KIDSCREEN-10 index in June and September 2021. To adjust for non-response bias, inverse probability weighting was applied. The potential effects of both household income and education (lower vs. higher) were estimated in generalized linear mixed models, based on prior assumptions presented in directed acyclic graphs. Our cohort comprised 660 students aged 7-19 years. In June 2021, 11.3% reported low HRQoL, whereas in September 2021, this increased to 13.7%, with adolescent girls more frequently reporting low HRQoL than boys and younger children at both time points (20% and 29%). While there was no statistically significant total effect of lower household income on HRQoL, a negative effect of lower household education was statistically significant (β = -2.15, SE = 0.95, 95% CI = -4.01 to -0.29, p = 0.024). In summary, students’ HRQoL in mid-2021 was better than that documented in other studies conducted at pandemic onset. Female adolescents reported low HRQoL more often, and lower household education significantly reduced children's HRQoL. Support strategies for psychosocial wellbeing should consider socioeconomically disadvantaged children as important target groups.

SARS-CoV-2 variant of concern B.1.1.7: diagnostic accuracy of three antigen-detecting rapid tests (preprint)

Virus mutations have the potential to impact the accuracy of diagnostic tests. The SARS-CoV-2 B.1.1.7 lineage is defined by a large number of mutations in the spike gene and four in the nucleocapsid (N) gene. Most commercially available SARS-CoV-2 antigen-detecting rapid tests (Ag-RDTs) target the viral N-protein, encoded by the N-gene. We conducted a manufacturer-independent, prospective diagnostic accuracy study of three SARS-CoV-2 Ag-RDTs that are currently under review by the WHO Emergency Use Listing Procedure (Espline - Fujirebio Inc.; Sure Status - Premier Medical Corporation Private Limited; Mologic - Mologic Ltd.) and report here on an additional sub-analysis regarding the B.1.1.7 lineage. During the study, in Berlin and Heidelberg, Germany, from 20 January to 15 April 2021, B.1.1.7 rapidly became the dominant SARS-CoV-2 lineage at the testing sites and was detected in 220 (62%) of SARS-CoV-2 RT-PCR positive patients. All three Ag-RDTs yielded comparable sensitivities irrespective of an infection with the B.1.1.7 lineage or not. There is only limited data on how N-gene mutations in variants of concern may impact Ag-RDTs. Currently, no major changes to test performance are anticipated. However, test developers and health authorities should assess and monitor the impact of emerging variants on the accuracy of Ag-RDTs.

Emergence of the SARS-CoV-2 B.1.1.7 lineage and its characteristics at an outpatient testing site in Berlin, Germany, January-March 2021 (preprint)

Within five weeks in early 2021, B.1.1.7 became the dominant SARS-CoV-2 lineage at an outpatient testing site in Berlin. Characteristics including Ct-values of 193 and 125 recently ill outpatients with B.1.1.7 and wildtype virus, respectively, were similar, except for more commonly reported sore throat and travel, and less frequently stated loss of smell and taste in the former.

Evaluation of accuracy, exclusivity, limit-of-detection and ease-of-use of LumiraDx™ - Antigen-detecting point-of-care device for SARS-CoV-2 (preprint)

BackgroundRapid antigen-detecting tests (Ag-RDTs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transform pandemic control. Thus far, sensitivity ([≤]85%) of lateral-flow assays has limited scale-up. Conceivably, microfluidic immunofluorescence Ag-RDTs could increase sensitivity for SARS-CoV-2 detection. Materials and MethodsThis multi-centre diagnostic accuracy study investigated performance of the microfluidic immunofluorescence LumiraDx assay, enrolling symptomatic and asymptomatic participants with suspected SARS-CoV-2 infection. Participants collected a supervised nasal mid-turbinate (NMT) self-swab for Ag-RDT testing, in addition to a professionally-collected nasopharyngeal (NP) swab for routine testing with reverse transcriptase polymerase chain reaction (RT-PCR). Results were compared to calculate sensitivity and specificity. Sub-analyses investigated the results by viral load, symptom presence and duration. An analytical study assessed exclusivity and limit-of-detection (LOD). In addition, we evaluated ease-of-use. ResultsStudy conduct was between November 2nd 2020 and January 21st 2021. 761 participants were enrolled, with 486 participants reporting symptoms on testing day. 120 out of 146 RT-PCR positive cases were detected positive by LumiraDx, resulting in a sensitivity of 82.2% (95% CI: 75.2%-87.5%). Specificity was 99.3% (CI: 98.3-99.7%). Sensitivity was increased in individuals with viral load [≥] 7 log10 SARS-CoV2 RNA copies/ml (93.8%; CI: 86.2%-97.3%). Testing against common respiratory commensals and pathogens showed no cross-reactivity and LOD was estimated to be 2-56 PFU/mL. The ease-of-use-assessment was favourable for lower throughput settings. ConclusionThe LumiraDx assay showed excellent analytical sensitivity, exclusivity and clinical specificity with good clinical sensitivity using supervised NMT self-sampling.

Anterior nasal versus nasal mid-turbinate sampling for a SARS-CoV-2 antigen-detecting rapid test: does localisation or professional collection matter? (preprint)

ObjectivesThe aim of this diagnostic accuracy study was direct comparison of two different nasal sampling methods for an antigen-based rapid diagnostic test (Ag-RDT) that detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, the accuracy and feasibility of self-sampling was evaluated. MethodsThis manufacturer-independent, prospective diagnostic accuracy study, compared professional anterior nasal (AN) and nasal mid-turbinate (NMT) sampling for a WHO-listed SARS-CoV-2 Ag-RDT. A second group of participants collected a NMT sample themselves and underwent a professional nasopharyngeal swab for comparison. The reference standard was real-time polymerase chain reaction (RT-PCR) using combined oro-/nasopharyngeal sampling. Individuals with high suspicion of SARS-CoV-2 infection were tested. Sensitivity, specificity, and percent agreement were calculated. Self-sampling was observed without intervention. Feasibility was evaluated by observer and participant questionnaires. ResultsAmong 132 symptomatic adults, both professional AN- and NMT-sampling yielded a sensitivity of 86.1% (31/36 RT-PCR positives detected; 95%CI: 71.3-93.9) and a specificity of 100.0% (95%CI: 95.7-100). The positive percent agreement (PPA) was 100% (95%CI: 89.0-100). Among 96 additional adults, self NMT- and professional NP-sampling yielded an identical sensitivity of 91.2% (31/34; 95%CI 77.0-97.0). Specificity was 98.4% (95%CI: 91.4-99.9) with NMT- and 100.0% (95%CI: 94.2-100) with NP-sampling. The PPA was 96.8% (95%CI: 83.8-99.8). Most participants (85.3%) considered self-sampling as easy to perform. ConclusionProfessional AN- and NMT-sampling are of equivalent accuracy for an Ag-RDT in ambulatory symptomatic adults. Participants were able to reliably perform the NMT-sampling themselves, following written and illustrated instructions. Nasal self-sampling will likely facilitate scaling of SARS-CoV-2 antigen testing.

SARS-CoV-2 infection and transmission in school settings during the second wave in Berlin, Germany: a cross-sectional study (preprint)

Background: School attendance during the SARS-CoV-2 pandemic is intensely debated. Modelling studies suggest that school closures contribute to community transmission reduction. However, data among school-attending students and staff are scarce. In November 2020, we examined SARS-CoV-2 infections and seroreactivity in 24 randomly selected school classes and connected households in Berlin, Germany. Methods: Students and school staff were examined, oro-nasopharyngeal swabs and blood samples collected, and SARS-CoV-2 infection and IgG antibodies detected by RT-PCR and ELISA. Household members performed self-swabs. Individual and institutional infection prevention and control measures were assessed. Classes with SARS-CoV-2 infection and connected household members were re-tested after one week. Findings: 1119 participants were examined, including 177 primary and 175 secondary school students, 142 staff, and 625 household members. Participants reported mainly cold symptoms (19.4%). SARS-CoV-2 infection occurred in eight of 24 classes affecting each 1-2 individuals. Infection prevalence was 2.7% (95%CI, 1.2-5.0%; 9/338), 1.4% (0.2-5.1%; 2/140), and 2.3% (1.3-3.8%; 14/611) among students, staff and household members, respectively, including quarantined persons. Six of nine infected students were asymptomatic. Prevalence increased with inconsistent facemask use in school, way to school on foot, and case-contacts outside school. IgG antibodies were detected in 2.0% (0.8-4.1%; 7/347), 1.4% (0.2-5.0%; 2/141) and 1.4% (0.6-2.7%; 8/576), respectively. For three of nine households with infection(s) detected at cross-sectional assessment, origin in school seemed possible. After one week, no school-related, secondary infections appeared in affected classes; the attack rate in connected households was 1.1%. Interpretation: These data suggest that school attendance under preventive measures is feasible, provided their rigorous implementation. In balancing threats and benefits of open versus closed schools during the pandemic, parents and society need to consider possible spill-overs into their households. Deeper insight is needed into the infection risks due to being a schoolchild as compared to attending school. Funding: Senate of Berlin.

SARS-CoV-2 patient self-testing with an antigen-detecting rapid test: a head-to-head comparison with professional testing (preprint)

Background Antigen-detecting rapid diagnostic tests (Ag-RDTs) have been widely recommended as a complement to RT-PCR. Considering the possibility of nasal self-sampling and the ease-of-use in performing the test, self-testing may be an option. Methods and Findings We performed a manufacturer-independent, prospective diagnostic accuracy study of nasal mid-turbinate self-sampling and self-testing when using a WHO-listed SARS-CoV-2 Ag-RDT. Symptomatic participants suspected to have COVID-19 received written and illustrated instructions. Procedures were observed without intervention. For comparison, Ag-RDTs with nasopharyngeal sampling were professionally performed. Estimates of agreement, sensitivity, and specificity relative to RT-PCR on a combined oro-/nasopharyngeal sample were calculated. Feasibility was evaluated by observer and participant questionnaires. Among 146 symptomatic adults, 40 (27.4%) were RT-PCR-positive for SARS-CoV-2. Sensitivity with self-testing was 82.5% (33/40 RT-PCR positives detected; 95% CI 68.1-91.3), and 85.0% (34/40; 95% CI 70.9-92.9) with professional testing. The positive percent agreement between self-testing and professional testing on Ag-RDT was 91.4% (95% CI 77.6-97.0), and negative percent agreement 99.1% (95% CI 95.0-100). At high viral load (>7.0 log10 SARS-CoV-2 RNA copies/ml), sensitivity was 96.6% (28/29; 95% CI 82.8-99.8) for both self- and professional testing. Deviations in sampling and testing (incomplete self-sampling or extraction procedure, or imprecise volume applied on the test device) were observed in 25 out of the 40 PCR-positives. Participants were rather young (mean age 35 years) and educated (59.6% with higher education degree). Most participants (80.9%) considered the Ag-RDT as rather easy to perform. Conclusion Ambulatory participants suspected for SARS-CoV-2 infection were able to reliably perform the Ag-RDT and test themselves. Procedural errors might be reduced by refinement of the Ag-RDTs for self-testing, such as modified instructions for use or product design/procedures. Self-testing may result in more wide-spread and more frequent testing. Paired with the appropriate information and education of the general public about the benefits and risks, self-testing may therefore have significant impact on the pandemic.

SARS-CoV-2 infection, risk perception, behaviour, and preventive measures at schools in Berlin, Germany, during the early post-lockdown phase: A cross-sectional study (preprint)

BackgroundBriefly before the first peak of the COVID-19 pandemic in Berlin, Germany, schools closed in mid-March 2020 for six weeks. Following re-opening, schools gradually resumed operation at a reduced level for nine weeks preceding the summer holidays. AimDuring this phase, we conducted a situational assessment in schools among students and teachers as to infection status, symptoms, affective, behavioural, educational issues, and preventive measures. MethodsAt twenty-four randomly selected primary and secondary schools, one class each was examined. Oro-nasopharyngeal swabs and capillary blood samples were collected to assess SARS-CoV-2 infection (PCR) and specific IgG (ELISA), respectively. Medical history, household and schooling characteristics, leisure time activities, fear of infection, risk perception, hand hygiene, physical distancing, and facemask wearing were assessed. ResultsAmong 535 participants (385 students, 150 staff), one teenager was SARS-CoV-2 infected (0.2%), and seven individuals exhibited specific IgG (1.3%); 16% reported symptoms upon examination, and 48% in the preceding 14 days. Compared to before the pandemic, the proportion of leisure time spent as screen-time increased, and the majority of primary school students reported reduced physical activity. Fear of infection and risk perception were relatively low, but acceptance of adapted health behaviours was high. Governmental preventive measures were adequately implemented, with primary schools performing better than secondary schools. ConclusionIn this phase of rare infection and low seroreactivity, individual and school-level infection prevention and control measures were largely adhered to. Nevertheless, vigilance, continued and proactive preventive measures, and well-rehearsed reaction options are essential to cope with increasing pandemic activity.

SARS-CoV-2 infections in kindergartens and associated households at the start of the second wave in Berlin, Germany - a cross sectional study (preprint)

ObjectivesThe comparatively large proportion of asymptomatic SARS-CoV-2 infections in the youngest children opens up the possibility that kindergartens represent reservoirs of infection. However, actual surveys in kindergartens beyond individual outbreaks are rare. At the beginning of the second pandemic wave in Berlin, Germany, i.e., end of September 2020, we screened SARS-CoV-2 infections among kindergarten children, staff and connected household members. MethodsTwelve kindergartens were randomly selected in the Berlin metropolitan area, and a total of 720 participants were recruited (155 pre-school children, 78 staff, 487 household members). Participants were briefly examined and interviewed, and SARS-CoV-2 infections and anti-SARS-Cov-2 IgG antibodies were assessed. ResultsSigns and symptoms, largely resembling common cold, were present in 24.2% of children and 28.9% of staff. However, no SARS-CoV-2 infection was detected among 701 PCR-tested individuals, and only one childcare worker showed IgG seroreactivity (0.15%; 1/672). ConclusionsAgainst a backdrop of increased pandemic activity in the community, this cross-sectional study does not suggest that kindergartens are silent transmission reservoirs. Nevertheless, at increasing pandemic activity, reinforced precautionary measures and repeated routine testing appears advisable.

Head-to-head comparison of SARS-CoV-2 antigen-detecting rapid test with professional-collected anterior nasal versus nasopharyngeal swab (preprint)

BackgroundNasopharyngeal (NP) swab samples for antigen-detecting rapid diagnostic tests (Ag-RDTs) require qualified healthcare professionals and are frequently perceived as uncomfortable by patients. MethodsWe performed a manufacturer-independent, prospective diagnostic accuracy study, comparing professional-collected nasal mid-turbinate (NMT) to nasopharyngeal swab, using the test kits of a WHO-listed SARS-CoV-2 Ag-RDT (STANDARD Q COVID-19 Ag Test, SD Biosensor), which is also being distributed by Roche. Individuals with high suspicion for COVID-19 infection were tested. The reference standard was RT-PCR using a combined oro-/nasopharyngeal swab sample. Percent positive and negative agreement, as well as sensitivity and specificity were calculated. ResultsAmong the 179 participants, 41 (22.9%) tested positive for SARS-CoV-2 by RT-PCR. The positive percent agreement of the two different sampling techniques for the Ag-RDT was 93.5% (CI 79.3-98.2). The negative percent agreement was 95.9% (CI 91.4-98.1). The Ag-RDT with NMT-sampling showed a sensitivity of 80.5% (33/41 PCR positives detected; CI 66.0-89.8) and specificity of 98.6% (CI 94.9-99.6) compared to RT-PCR. The sensitivity with NP-sampling was 73.2% (30/41 PCR positives detected; CI 58.1-84.3) and specificity was 99.3% (CI 96.0-100). In patients with high viral load (>7.0 log10 SARS-CoV-2 RNA copies/swab), the sensitivity of the Ag-RDT with NMT-sampling was 100% and 94.7% with NP-sampling. ConclusionThis study demonstrates that sensitivity of a WHO-listed SARS-CoV-2 Ag-RDT using a professional nasal-sampling kit is at least equal to that of the NP-sampling kit, although confidence intervals overlap. Of note, differences in the IFUs of the test procedures could have contributed to different sensitivities. NMT-sampling can be performed with less training, reduces patient discomfort, and it enables scaling of antigen testing strategies. Additional studies of patient self-sampling should be considered to further facilitate the scaling-up of Ag-RDT testing.

Decontamination of Common Healthcare Facility Surfaces Contaminated with SARS-CoV-2 using Peracetic Acid Dry Fogging (preprint)

BackgroundThe SARS-Cov-2 pandemic has highlighted the urgent need for safe and effective surface decontamination methods, particularly in healthcare settings. MethodsThe effectiveness of peracetic acid (PAA) dry fogging in decontaminating common healthcare setting surfaces was evaluated after experimentally contaminating nine surfaces (stainless steel, latex painted wood, unsealed hardwood, melamine countertop, vinyl flooring, clear plastic, faux leather, computer keyboard button and smartphone touch screen) with more than 106 TCID50 of SARS-CoV-2. ResultsWhen fumigated with PAA dry fog for an hour, no infectious SARS-CoV-2 virus was recovered from experimentally inoculated coupons of representing nine different surface types. In contrast, high titer recovery of infectious virus was demonstrated for corresponding untreated drying controls of the same materials. ConclusionStandard surface decontaminating processes, including sprays and wipes, are laborious and often cannot completely decontaminate sensitive electronic equipment. The ease of use, low cost and overall effectiveness of a PAA dry fogging suggest it should be considered for decontaminating settings, particularly intensive care units where severely ill SARS-CoV-2 patients are cared for.

Evaluation of the accuracy and ease-of-use of Abbott PanBio - A WHO emergency use listed, rapid, antigen-detecting point-of-care diagnostic test for SARS-CoV-2 (preprint)

BackgroundDiagnostics are essential for controlling the pandemic. Identifying a reliable and fast diagnostic is needed to support testing. We assessed performance and ease-of-use of the Abbott PanBio antigen-detecting rapid diagnostic test (Ag-RDT). MethodsThis prospective, multi-centre diagnostic accuracy study enrolled at two sites in Germany. Following routine testing with RT-PCR, a second study-exclusive swab was performed for Ag-RDT testing. Routine swabs were nasopharyngeal (NP) or combined NP/oropharyngeal (OP) whereas the study-exclusive swabs were NP. To evaluate performance, sensitivity and specificity were assessed overall and in predefined sub analyses accordingly to cycle-threshold values, days of symptoms, disease severity and study site. Additionally, an ease-of-use assessment and System Usability Scale (SUS) were performed. Findings1108 participants were enrolled between Sept 28 and Oct 30, 2020. Of these, 106 (9{middle dot}6%) were PCR-positive. The Abbott PanBio detected 92/106 PCR-positive participants with a sensitivity of 86{middle dot}8% (95% CI: 79{middle dot}0% - 92{middle dot}0%) and a specificity of 99{middle dot}9% (95% CI: 99{middle dot}4%-100%). The sub analyses indicated that sensitivity was 95{middle dot}8% in CT-values <25 and within the first seven days from symptom onset. The test was characterized as easy to use (SUS: 86/100) and considered suitable for point-of- care settings. InterpretationThe Abbott PanBio Ag-RDT performs well for SARS-CoV-2 testing in this large manufacturer independent study, confirming its WHO recommendation for Emergency Use in settings with limited resources. FundingThe Foundation of Innovative New Diagnostics supplied the test kits for the study. The internal funds from the Heidelberg University as well as the Charite Berlin supported this study.

Monitoring for COVID-19 by universal testing in a homeless shelter in Germany: a prospective feasibility cohort study (preprint)

Background: Living conditions in homeless shelters may facilitate the transmission of COVID-19. Social determinants and pre-existing health conditions place homeless people at increased risk of severe disease. Described outbreaks in homeless shelters resulted in high proportions of infected residents and staff members. In addition to other infection prevention strategies, regular shelter-wide (universal) testing for COVID-19 may be valuable, depending on the level of community transmission and when resources permit. Methods: This was a prospective feasibility cohort study to evaluate universal testing for COVID-19 at a homeless shelter with 106 beds in Berlin, Germany. Co-researchers were recruited from the shelter staff. A PCR analysis of saliva or self-collected nasal/oral swab was performed weekly over a period of 3 weeks in July 2020. Acceptability and implementation barriers were analyzed by process evaluation using mixed methods including evaluation sheets, focus group discussion and a structured questionnaire. Results: Ninety-three out of 124 (75%) residents were approached to participate in the study. Fifty-one out of the 93 residents (54.8%) gave written informed consent. High retention rates (88.9% - 93.6%) of a weekly respiratory specimen were reached, but repeated collection attempts, as well as assistance were required. A self-collected nasal/oral swab was considered easier and more hygienic to collect than a saliva specimen. No resident was tested positive. Language barriers were the main reason for non-participation. Flexibility of sample collection schedules, the use of video and audio materials, and concise written information were the main recommendations of the co-researchers for future implementation. Conclusion: Voluntary universal testing for COVID-19 is feasible in homeless shelters. Universal testing of high-risk facilities will require flexible approaches, considering the level of the community transmission, the available resources, and the local recommendations. Lack of human resources and laboratory capacity may be a major barrier for implementation of universal testing, requiring adapted approaches compared to standard individual testing. Assisted self-collection of specimens and barrier free communication may facilitate implementation in homeless shelters. Program planning must consider needs and life situation of homeless people, and guarantee confidentiality and autonomy.

Studying the pathophysiology of coronavirus disease 2019 - a protocol for the Berlin prospective COVID-19 patient cohort (Pa- COVID-19) (preprint)

Purpose Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a global health emergency. Pa-COVID-19 aims to provide comprehensive data on clinical course, pathophysiology, immunology and outcome of COVID-19, in order to identify prognostic biomarkers, clinical scores, and therapeutic targets for improved clinical management and preventive interventions. Methods Pa-COVID-19 is a prospective observational cohort study of patients with confirmed SARS-CoV-2 infection treated at Charite - Universitaetsmedizin Berlin. We collect data on epidemiology, demography, medical history, symptoms, clinical course, pathogen testing and treatment. Systematic, serial blood sampling will allow deep molecular and immunological phenotyping, transcriptomic profiling, and comprehensive biobanking. Longitudinal data and sample collection during hospitalization will be supplemented by long-term follow-up. Results Outcome measures include the WHO clinical ordinal scale on day 15 and clinical, functional and health-related quality of life assessments at discharge and during follow-up. We developed a scalable dataset to (i) suit national standards of care (ii) facilitate comprehensive data collection in medical care facilities with varying resources and (iii) allow for rapid implementation of interventional trials based on the standardized study design and data collection. We propose this scalable protocol as blueprint for harmonized data collection and deep phenotyping in COVID-19 in Germany. Conclusion We established a basic platform for harmonized, scalable data collection, pathophysiological analysis, and deep phenotyping of COVID-19, which enables rapid generation of evidence for improved medical care and identification of candidate therapeutic and preventive strategies. The electronic database accredited for interventional trials allows fast trial implementation for candidate therapeutic agents.