Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and monoclonal antibodies

Due to numerous mutations in the spike protein, the SARS-CoV-2 variant of concern Omicron (B.1.1.529) raises serious concerns since it may significantly limit the antibody-mediated neutralization and increase the risk of reinfections. While a rapid increase in the number of cases is being reported worldwide, until now there has been uncertainty about the efficacy of vaccinations and monoclonal antibodies. Our in vitro findings using authentic SARS-CoV-2 variants indicate that in contrast to the currently circulating Delta variant, the neutralization efficacy of vaccine-elicited sera against Omicron was severely reduced highlighting T-cell mediated immunity as essential barrier to prevent severe COVID-19. Since SARS-CoV-2 Omicron was resistant to casirivimab and imdevimab, genotyping of SARS-CoV-2 may be needed before initiating mAb treatment. Variant-specific vaccines and mAb agents may be required to treat COVID-19 due to Omicron and other emerging variants of concern.

Characterization of the humoral immune response to BNT162b2 in elderly residents of long-term care facilities five to seven months after vaccination

The elderly residing in long-term care facilities (LTCFs) are a group at high risk for COVID-19. Hence, monitoring of the vaccine-based immunity has a pivotal role in identifying strategies to provide optimal protection in this population. We examined the immune response to the mRNA vaccine BNT162b2 against COVID-19 five to seven months after completing a two-dose regimen. We determined significantly lower anti-SARS-CoV-2 antibody titers in 298 SARS-CoV-2 naive residents who were at least 75 years of age (mean 51.60 BAU/ml) (median age 87 years, range 75 to 101 years) when compared to health care workers (HCWs) aged 18 to 70 years (mean 156.99 BAU/ml, p < 0.001). Of the SARS-CoV-2 naive residents, 29 had detectable neutralizing antibodies against the Delta variant (9.5%), and 14 of those (48.3%) only had a borderline titer of 1:10. Of 114 HCWs, 36 (31.6%) had detectable neutralizing antibodies. In a group of 14 elderly residents who had had a PCR-confirmed breakthrough infection, the mean antibody titer was significantly higher than in the other two groups (3199.65 BAU/mL) (p < 0.001), and 12 (85.7%) had detectable neutralizing antibodies against the Delta variant. Our data demonstrate that 90.5% of elderly residents of LTCFs had no detectable neutralization-competent antibodies against the dominant Delta variant five to seven months after vaccination, and that neutralizing antibody titers were restored following a break-through infection. Our results suggest that both residents and health care workers in LTCFs would benefit from a booster vaccine six months after completing the two-dose schedule or earlier.

Longitudinal testing for SARS-CoV-2 RNA in day care centers in Hesse, Germany, during increased local incidence and with VOC Alpha as dominant variant: Results of the SAFE KiDS 2 and SAFE KiDS 3 study

In the summer of 2020, we investigated the rate of inapparent shedding of SARS-CoV-2 in a representative sample of day care centers from Hesse, Germany, and found a low positivity rate during a period of low local community spread. To investigate the influence of a high local incidence setting, we conducted the SAFE KiDS 2 study. 577 children and 334 staff members of 47 day care centers were tested for respiratory and gastrointestinal shedding of SARS-CoV-2, and three infections with SARS-CoV-2 in the infectious period were detected. We conclude that viral shedding occurred infrequently while the original "wild-type" variant was dominant. The more transmissible SARS-CoV-2 variant Alpha (B.1.1.7) became the dominant strain after SAFE KiDS 2 was concluded. The SAFE KiDS 3 study investigated the impact of the Alpha variant of SARS-CoV-2 on inapparent viral shedding in the day care setting. In this study, 756 children and 226 staff members from 46 day care centers provided self-collected saliva swabs, the so-called "Lollipop" swabs, which were tested by RT-PCR. In the four-week study period, none of the participants tested positive for SARS-CoV-2 RNA, demonstrating that inapparent shedding of SARS-CoV-2 in the day care setting was also rare during the dominance of the Alpha variant. The influence of the variant of concern Delta on day care centers has yet to be studied.

At-home self-testing of teachers with a SARS-CoV-2 rapid antigen test to reduce potential transmissions in schools

BackgroundRapid antigen tests for SARS-CoV-2 became available recently, offering an opportunity to vastly increase testing capacities. Antigen tests offer lower sensitivity than the gold standard, RT-PCR, but rapid sample-to-answer time. High-frequency testing with an antigen test may offset the lower sensitivity, and testing can be done with at-home collection of samples, offering potential benefit in screening efforts. In this study, we set out to evaluate the practical application of self-performed high-frequency antigen test in a school setting. MethodA total of 711 teachers from 86 schools were enrolled in a seven-week study. After instruction, participants tested themselves every 48 hours at home with a rapid antigen test for SARS-CoV-2 (target: nucleocapsid protein) in a self-collected anterior nasal swab. Positive results in the antigen test were confirmed via RT-PCR from the same sample that had been determined to be positive by the study participant. A questionnaire was given to all participants to evaluate whether the test failed to detect infection. Findings10 836 tests from 602 teachers were recorded and analyzed. A total of five confirmed cases of viral shedding of SARS-CoV-2 was detected by use of the antigen test. One study participant with a SARS-CoV-2 infection was presymptomatic and four were mildly symptomatic at the time of the antigen test. Sixteen false positive antigen tests (0.15% of all tests) were reported, predominantly when the local incidence in the general population was low. In four cases, the study participant reported that a PCR had detected a SARS-CoV-2 infection, but the antigen test was negative, indicating a false negative result. InterpretationHigh-frequency, self-performed rapid antigen tests can detect individuals with a SARS-CoV-2 infection, and therefore potentially reduce transmissions. Testing may be most beneficial when applied during high local incidence of SARS-CoV-2 infections and when mild or atypical symptoms are present. To avoid a high rate of false positive results, a test with optimized specificity should be used. FundingThe study was commissioned and funded by the Hessian Ministry of Education and the Hessian Ministry of Integration and Social Affairs.

Longitudinal testing for respiratory and gastrointestinal shedding of SARS-CoV-2 in day care centres in Hesse, Germany. Results of the SAFE KiDS Study

BackgroundWith the pandemic of SARS-CoV-2 ongoing in Europe in July of 2020, day care centres were reopened in the state of Hesse, Germany, after the lockdown. The role young children play in the dynamics of the transmission was unknown. MethodsWe conducted a longitudinal study over a period of 12 weeks (18th of June 2020 to 10th of September, 2020) to screen attendees and staff from day care centres in the state of Hesse, Germany, for both respiratory and gastrointestinal shedding of SARS-CoV-2. 825 children (age range 3 months to 8 years) and 372 staff members from 50 day care centres, which were chosen representatively from throughout the state, participated in the study. Parents were asked to perform both a buccal mucosa and an anal swab on their children once a week. Staff were asked to self-administer the swabs. RT-PCRs for SARS-CoV-2 were performed in a multiple-swab pooling protocol. Findings7,366 buccal mucosa swabs and 5,907 anal swabs were analysed. No respiratory or gastrointestinal shedding of SARS-CoV-2 was detected in any of the children. Shedding of SARS-CoV-2 could be detected in two staff members from distinct day care centres. One was asymptomatic at the time of testing, and one was symptomatic. InterpretationRespiratory or gastrointestinal shedding of SARS-CoV-2 in children or staff members in day care centres was very rare in the context of low community activity. The data indicate day care centres do not pose a reservoir for SARS-CoV-2 in a low prevalence setting, no inapparent transmissions were observed. FundingThe study was commissioned by the Hessian Ministry of Social Affairs and Integration and was supported by Roche Diagnostics, Basel, Switzerland.