Low impact of regular PCR testing on presence at work site during the COVID-19 pandemic: experiences during an open observational study in Lower Saxony 2020-21.

BACKGROUND: Since social distancing during the COVID-19-pandemic had a profound impact on professional life, this study investigated the effect of PCR testing on on-site work. METHODS: PCR screening, antibody testing, and questionnaires offered to 4,890 working adults in Lower Saxony were accompanied by data collection on demographics, family status, comorbidities, social situation, health-related behavior, and the number of work-related contacts. Relative risks (RR) with 95 % confidence intervals were estimated for the associations between regular PCR testing and other work and health-related variables, respectively, and working on-site. Analyses were stratified by the suitability of work tasks for mobile office. RESULTS: Between April 2020 and February 2021, 1,643 employees underwent PCR testing. Whether mobile working was possible strongly influenced the work behavior. Persons whose work was suitable for mobile office (mobile workers) had a lower probability of working on-site than persons whose work was not suitable for mobile office (RR = 0.09 (95 % CI: 0.07 - 0.12)). In mobile workers, regular PCR-testing was slightly associated with working on-site (RR = 1.19 (0.66; 2.14)). In those whose working place was unsuitable for mobile office, the corresponding RR was 0.94 (0.80; 1.09). Compared to persons without chronic diseases, chronically ill persons worked less often on-site if their workplace was suitable for mobile office (RR = 0.73 (0.40; 1.33)), but even more often if their workplace was not suitable for mobile office (RR = 1.17 (1.04; 1.33)). CONCLUSION: If work was suitable for mobile office, regular PCR-testing did not have a strong effect on presence at the work site. TRIAL REGISTRATION: An ethics vote of the responsible medical association (Lower Saxony, Germany) retrospectively approved the evaluation of the collected subject data in a pseudonymized form in the context of medical studies (No. Bo/30/2020; Bo/31/2020; Bo/32/2020).

Students' age and parental level of education influence COVID-19 vaccination hesitancy.

Widespread vaccination in pursuit of herd immunity has been recognized as the most promising approach to ending the global pandemic of coronavirus disease 19 (COVID-19). The vaccination of children and adolescents has been extensively debated and the first COVID-19 vaccine is now approved in European countries for children aged > 12 years of age. Our study investigates vaccination hesitancy in a cohort of German secondary school students. We assessed 903 students between age 9 and 20 in the period between 17 May 2021 and 30 June 2021. 68.3% (n = 617) reported intention to undergo COVID-19 vaccination, while 7% (n = 62) did not want to receive the vaccine and 15% (n = 135) were not yet certain. Age and parental level of education influenced COVID-19 vaccine hesitancy. Children under the age of 16 as well as students whose parents had lower education levels showed significantly higher vaccine hesitancy.  Conclusion: Identifying subsets with higher vaccination hesitancy is important for targeting public information campaigns in support of immunization. What is Known: • The willingness to receive COVID-19 vaccination among adults in Europe is about 70%, but data for children and adolescents is lacking. • The lack of immunization in younger cohorts represents a significant barrier to achieving herd immunity, and also leaves children and adolescents vulnerable to acute and long-term morbidity from natural COVID-19 infections. What is New: • Intention-to-vaccinate among children and adolescents is high (~ 70%); conversely, vaccination hesitancy is low. • Age and parental level of education influenced COVID-19 vaccine hesitancy among children and adolescents.

Mobile SARS­CoV­2 screening facilities for rapid deployment and university-based diagnostic laboratory.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created a public crisis. Many medical and public institutions and businesses went into isolation in response to the pandemic. Because SARS-CoV-2 can spread irrespective of a patient's course of disease, these institutions' continued operation or reopening based on the assessment and control of virus spread can be supported by targeted population screening. For this purpose, virus testing in the form of polymerase chain reaction (PCR) analysis and antibody detection in blood can be central. Mobile SARS-CoV-2 screening facilities with a built-in biosafety level (BSL)-2 laboratory were set up to allow the testing offer to be brought close to the subject group's workplace. University staff members, their expertise, and already available equipment were used to implement and operate the screening facilities and a certified diagnostic laboratory. This operation also included specimen collection, transport, PCR and antibody analysis, and informing subjects as well as public health departments. Screening facilities were established at different locations such as educational institutions, nursing homes, and companies providing critical supply chains for health care. Less than 4 weeks after the first imposed lockdown in Germany, a first mobile testing station was established featuring a build-in laboratory with two similar stations commencing operation until June 2020. During the 15-month project period, approximately 33,000 PCR tests and close to 7000 antibody detection tests were collected and analyzed. The presented approach describes the required procedures that enabled the screening facilities and laboratories to collect and process several hundred specimens each day under difficult conditions. This report can assist others in establishing similar setups for pandemic scenarios.

Vascular implants - new aspects for in situ tissue engineering.

Conventional synthetic vascular grafts require ongoing anticoagulation, and autologous venous grafts are often not available in elderly patients. This review highlights the development of bioartificial vessels replacing brain-dead donor- or animal-deriving vessels with ongoing immune reactivity. The vision for such bio-hybrids exists in a combination of biodegradable scaffolds and seeding with immune-neutral cells, and here different cells sources such as autologous progenitor cells or stem cells are relevant. This kind of in situ tissue engineering depends on a suitable bioreactor system with elaborate monitoring systems, three-dimensional (3D) visualization and a potential of cell conditioning into the direction of the targeted vascular cell phenotype. Necessary bioreactor tools for dynamic and pulsatile cultivation are described. In addition, a concept for design of vasa vasorum is outlined, that is needed for sustainable nutrition of the wall structure in large caliber vessels. For scaffold design and cell adhesion additives, different materials and technologies are discussed. 3D printing is introduced as a relatively new field with promising prospects, for example, to create complex geometries or micro-structured surfaces for optimal cell adhesion and ingrowth in a standardized and custom designed procedure. Summarizing, a bio-hybrid vascular prosthesis from a controlled biotechnological process is thus coming more and more into view. It has the potential to withstand strict approval requirements applied for advanced therapy medicinal products.

Combined Prospective Seroconversion and PCR Data of Selected Cohorts Indicate a High Rate of Subclinical SARS-CoV-2 Infections-an Open Observational Study in Lower Saxony, Germany.

Despite lockdown measures, intense symptom-based PCR, and antigen testing, the SARS-CoV-2 pandemic spread further. In this open observational study conducted in Lower Saxony, Germany, voluntary SARS-CoV-2 PCR tests were performed from April 2020 until June 2021, supported by serum antibody testing to prove whether PCR testing in subjects with none or few symptoms of COVID-19 is a suitable tool to manage the pandemic. In different mobile stations, 4,817 subjects from three different working fields participated in the PCR testing. Serum antibody screening using the SARS-CoV-2 ViraChip IgG (Viramed, Germany) and the Elecsys Anti-SARS-CoV-2 assay (Roche, Germany) was performed alongside virus neutralization testing. Subjects were questioned regarding comorbidities and COVID-19 symptoms. Fifty-one subjects with acute SARS-CoV-2 infection were detected of which 31 subjects did not show any symptoms possibly characteristic for COVID-19. An additional 37 subjects reported a previous SARS-CoV-2 infection (total prevalence 1.82%). Seroconversion was discovered in 58 subjects with known SARS-CoV-2 infection and in 58 subjects that never had a positive PCR test. The latter had a significantly lower Charlson Comorbidity Index, and one third of them were asymptomatic. In 50% of all seroconverted subjects, neutralizing serum antibodies (NAbs) were detectable in parallel to N/S1 (n = 16) or N/S1/S2 antigen specific antibodies (n = 40) against SARS-CoV-2. NAb titers decreased within 100 days after PCR-confirmed SARS-CoV-2 acute infection by at least 2.5-fold. A relatively high rate of subclinical SARS-CoV-2 infections may contribute to the spread of SARS-CoV-2, suggesting that in addition to other intervention strategies, systematic screening of asymptomatic persons by PCR testing may significantly enable better pandemic control. IMPORTANCE Within this open observational study, repeated PCR (n > 4,700) and antibody screening (n > 1,600) tests were offered in three different working fields. The study identified 51 subjects with acute SARS-CoV-2 infection and 37 subjects reported to have had a positive PCR test taken externally. Thirty-one of the 51 subjects did not display any symptoms prior to testing. In addition, 58 subjects without PCR-confirmed SARS-CoV-2 infection were identified by seroconversion. Subjects, that had undergone SARS-CoV-2 infection without having noticed, more often had a low grade of immunization with no NAbs, but may have relevantly contributed to the spread of the pandemic. Based on these results, we suggest that both regular PCR and rapid test screening of symptomatic and asymptomatic individuals, specifically within groups or workplaces identifiable as having close quarter contact, thus increased infection transference risk, is necessary to better assess and therefore reduce the spread of a pandemic virus.

Signs of immunosenescence correlate with poor outcome of mRNA COVID-19 vaccination in older adults.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is effective in preventing COVID-19 hospitalization and fatal outcome. However, several studies indicated that there is reduced vaccine effectiveness among older individuals, which is correlated with their general health status1,2. How and to what extent age-related immunological defects are responsible for the suboptimal vaccine responses observed in older individuals receiving SARS-CoV-2 messenger RNA vaccine, is unclear and not fully investigated1,3-5. In this observational study, we investigated adaptive immune responses in adults of various ages (22-99 years old) receiving 2 doses of the BNT162b2 mRNA vaccine. Vaccine-induced Spike-specific antibody, and T and memory B cell responses decreased with increasing age. These responses positively correlated with the percentages of peripheral naïve CD4+ and CD8+ T cells and negatively with CD8+ T cells expressing signs of immunosenescence. Older adults displayed a preferred T cell response to the S2 region of the Spike protein, which is relatively conserved and a target for cross-reactive T cells induced by human 'common cold' coronaviruses. Memory T cell responses to influenza virus were not affected by age-related changes, nor the SARS-CoV-2-specific response induced by infection. Collectively, we identified signs of immunosenescence correlating with the outcome of vaccination against a new viral antigen to which older adults are immunologically naïve. This knowledge is important for the management of COVID-19 infections in older adults.

Children and Adolescents' Behavioral Patterns in Response to Escalating COVID-19 Restriction Reveal Sex and Age Differences.

PURPOSE: The COVID-19 pandemic affects students in a myriad of different ways. Our prospective, longitudinal study in a cohort of students in Hannover, Germany explores behavioral patterns during escalating COVID-19 restrictions. METHODS: In total, 777 students between the age of 9 and 20 were assessed for their activity engagement, travel patterns, and self-assessed compliance with protective recommendations at six time points between June 2020 and June 2021 (3,564 observations) and were monitored for severe acute respiratory syndrome coronavirus 2 infection by nasal swab polymerase chain reaction and serum antibody titers. RESULTS: Activity engagement decreased, but self-assessed compliance with measures such as mask wearing and social distancing was stable during escalating restrictions. Although we found no sex difference during the summer break, when incidence was lowest, females engaged in a higher variety of activities than males for all other time points. Older students engaged in more activities and self-assigned themselves lower compliance values than younger ones. Greater involvement in different activities was seen in households which traveled more frequently. Infection rate in our cohort was low (0.03% acute infections, 1.94% positive seroprevalence). DISCUSSION: Our study supports the view that, overall, students show high compliance with COVID-19 recommendations and restrictions. The identification of subsets, such as female and older students, with higher risk behavioral patterns should be considered when implementing public information campaigns. In light of the low infection rate in our cohort, we conclude that in-person learning can occur safely if extensive protective measures are in place and the incidence in the general population remains moderate.

Comparison of two antibody screening systems for SARS-CoV-2 antibody detection in recovered and vaccinated subjects - test performance and possible indicators for immunity.

BACKGROUND: Detection of seroconversion after SARS-CoV-2-infection or vaccination is relevant to discover subclinical cases and recognize patients with a possible immunity. OBJECTIVES: Test performance, effects of age, time-point of seroconversion and immune status regarding neutralizing antibodies (NAbs) and T-cell-reactivity were investigated. STUDY DESIGN: Two antibody assays (Viramed-Test for S/N-specific IgG, Roche-Test for N-specific IgA, -M, -G) were evaluated with classified samples. In total, 381 subjects aged 6-99 years, who had either recovered from the disease or had been vaccinated, were screened for SARS-CoV-2-specific antibodies. This screening was part of an open observational study with working adults. Additionally, children and adults were analyzed in a longitudinal COVID-19 study in schools. For immunity evaluation, virus neutralization tests and ELISpot tests were performed in a subgroup of subjects. RESULTS: Viramed revealed a slightly lower test performance than Roche, but test quality was equally well in samples from very young or very old donors. The time-point of seroconversion after the respective immunization detected by the two tests was not significantly different. N-specific antibodies, detected with Roche, highly correlated with NAbs in recovered subjects, whereas a positive Viramed-Test result was paralleled by a positive ELISpot result. CONCLUSION: Viramed-Test was not as sensitive as Roche-Test, but highly specific and beneficial to distinguish between recovered and vaccinated status. For both tests correlations with humoral and cellular immunity were found. Of note, the expected early detection of IgA and IgM by the Roche-Test did not prove to be an advantage over IgG testing by Viramed.

Automated Bioreactor System for the Cultivation of Autologous Tissue-Engineered Vascular Grafts.

In an aging society, diseases associated with irreversible damage of organs are frequent. An increasing percentage of patients requires bioartificial tissue or organ substitutes. Tissue engineering products depend on a well-defined process to ensure successful cultivation while meeting high regulatory demands. The goal of the presented work is the development of a bioreactor system for the cultivation of tissue-engineered vascular grafts (TEVGs) for autologous implantation and transition from a lab scale setup to standardized production. Key characteristics include (i) the automated reliable monitoring and control of a wide-range of parameters regarding implant conditioning, (ii) easy and sterile setup and operation, (iii) reasonable costs of disposables, and (iv) parallelization of automated cultivation processes. The presented prototype bioreactor system provides comprehensive physiologically conditioning, sensing, and imaging functionality to meet all requirements for the successful cultivation of vascular grafts on a productional scale.

An intelligent bioreactor system for the cultivation of a bioartificial vascular graft.

Cardiovascular disease is the most common cause of death, accounting for 31% of deaths worldwide. As purely synthetic grafts implicate concomitant anticoagulation and autologous veins are rare, tissue-engineered vascular grafts are urgently needed. For successful in vitro cultivation of a bioartificial vascular graft, the suitable bioreactor should provide conditions comparable to vasculogenesis in the body. Such a system has been developed and characterized under continuous and pulsatile flow, and a variety of sensors has been integrated into the bioreactor to control parameters such as temperature, pressure up to 500 mbar, glucose up to 4.5 g/L, lactate, oxygen up to 150 mbar, and flow rate. Wireless data transfer (using the ZigBee specification based on the IEEE 802.15.4 standard) and multiple corresponding sensor signal processing platforms have been implemented as well. Ultrasound is used for touchless monitoring of the growing vascular structure as a quality control before implantation (maximally achieved ultrasound resolution 65 µm at 15 MHz). To withstand the harsh conditions of steam sterilization (120°C for 20 min), all electronics were encapsulated. With such a comprehensive physiologically conditioning, sensing, and imaging bioreactor system, all the requirements for a successful cultivation of vascular grafts are available now.