SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies

SARS-CoV-2 Beta variant of concern (VOC) resists neutralization by major classes of antibodies from non-VOC COVID-19 patients and vaccinated individuals. Here, serum of Beta variant infected patients revealed reduced cross-neutralization of non-VOC virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of novel VOC-specific clonotypes and accommodation of VOC-defining amino acids into a major non-VOC antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with non-VOC-elicited antibodies, including a public VH1-58 clonotype targeting the RBD ridge independent of VOC mutations. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift with implications for design of next-generation vaccines and therapeutics. One sentence summarySARS-CoV-2 Beta variant elicits lineage-specific antibodies and antibodies with neutralizing breadth against wild-type virus and VOCs.

Enhanced fitness of SARS-CoV-2 variant of concern B.1.1.7, but not B.1.351, in animal models

Emerging variants of concern (VOCs) drive the SARS-CoV-2 pandemic. We assessed VOC B.1.1.7, now prevalent in several countries, and VOC B.1.351, representing the greatest threat to populations with immunity to the early SARS-CoV-2 progenitors. B.1.1.7 showed a clear fitness advantage over the progenitor variant (wt-S614G) in ferrets and two mouse models, where the substitutions in the spike glycoprotein were major drivers for fitness advantage. In the "superspreader" hamster model, B.1.1.7 and wt-S614G had comparable fitness, whereas B.1.351 was outcompeted. The VOCs had similar replication kinetics as compared to wt-S614G in human airway epithelial cultures. Our study highlights the importance of using multiple models for complete fitness characterization of VOCs and demonstrates adaptation of B.1.1.7 towards increased upper respiratory tract replication and enhanced transmission in vivo. Summary sentenceB.1.1.7 VOC outcompetes progenitor SARS-CoV-2 in upper respiratory tract replication competition in vivo.

Reactogenicity of homologous and heterologous prime-boost immunization with BNT162b2 and ChAdOx1-nCoV19: a prospective cohort study

Heterologous prime-boost vaccination is of increasing interest for COVID-19 vaccines. Evidence of rare thrombotic events associated with ChAdOx1-nCoV19 (Vaxzevria, ChAdOx) has lead several European countries to recommend a heterologous booster with mRNA vaccines for certain age groups (e.g. persons <60years in Germany), who have already received one dose of ChAdOx, although data on reactogenicity and safety of this vaccination regimen are still missing. Here we report reactogenicity data of homologous BNT162b2 (Comirnaty, BNT) or heterologous ChAdOx/BNT prime-boost immunisations in a prospective observational cohort study of 326 healthcare workers. Reactogenicity of heterologous ChAdOx/BNT booster vaccination was largely comparable to homologous BNT/BNT vaccination and overall well-tolerated. No major differences were observed in the frequency or severity of local reactions after either of the vaccinations. In contrast, notable differences between the regimens were observed for systemic reactions, which were most frequent after prime immunisation with ChAdOx (86%, 95CI: 79-91), and less frequent after homologous BNT/BNT (65%, 95CI: 56-72), or heterologous ChAdOx/BNT boosters (48%, 95CI: 36-59). This interim analysis supports the safety of currently recommended heterologous ChAdOx/BNT prime-boost immunisations with 12-week intervals.

Comparison of seven commercial SARS-CoV-2 rapid Point-of-Care Antigen tests

BackgroundAntigen point of care tests (AgPOCT) can accelerate SARS-CoV-2 testing. As first AgPOCT are becoming available, there is a growing interest in their utility and performance. MethodsHere we compare AgPOCT products by seven suppliers: the Abbott Panbio COVID-19 Ag Rapid Test; the RapiGEN BIOCREDIT COVID-19 Ag; the Healgen(R) Coronavirus Ag Rapid Test Cassette (Swab); the Coris Bioconcept Covid.19 Ag Respi-Strip; the R-Biopharm RIDA(R)QUICK SARS-CoV-2 Antigen; the NAL von minden NADAL COVID19-Ag Test; and the Roche/SD Biosensor SARS-CoV Rapid Antigen Test. Tests were evaluated on recombinant nucleoprotein, cultured endemic and emerging coronaviruses, stored clinical samples with known SARS-CoV-2 viral loads (n=138), stored samples from patients with respiratory agents other than SARS-CoV-2 (n=100), as well as self-sampled swabs from healthy volunteers (n=35). FindingsLimits of detection in six of seven tested products ranged between 2.08 x 106 and 2.88 x 107 copies per swab, the outlier at 1.58 x 1010 copies per swab. Specificities ranged between 98.53% and 100% in five products, with two outliers at 94.85% and 88.24%. False positive results were not associated with any specific respiratory agent. As some of the tested AgPOCT were early production lots, the observed issues with specificity are unlikely to persist. InterpretationThe sensitivity range of most AgPOCT overlaps with viral load figures typically observed during the first week of symptoms, which marks the infectious period in the majority patients. AgPOCTs with a limit of detection that approximates the virus concentration above which patients are infectious may enable shortcuts in decision-making in various areas of healthcare and public health.

A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model

The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC50 of 3.1 ng/ml. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 [A] revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2 neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.

Seroprevalence and correlates of SARS-CoV-2 neutralizing antibodies: Results from a population-based study in Bonn, Germany

BackgroundAccurate estimates of SARS-CoV-2 seroprevalence are crucial for the implementation of effective public health measures, but are currently largely lacking in regions with low infection rates. This is further complicated by inadequate test performance of many widely used serological assays. We therefore aimed to assess SARS-CoV-2 seroprevalence in a region with low COVID-19 burden, especially focusing on neutralizing antibodies that presumably constitute a major component of acquired immunity. MethodsWe invited all individuals who were enrolled in the Rhineland Study, an ongoing community-based prospective cohort study in people aged 30 years and above in the city of Bonn, Germany (N=5427). Between April 24th and June 30th, 2020, 4771 (88%) of these individuals participated in the serosurvey. Anti-SARS-CoV-2 IgG levels were measured using an ELISA assay, and all positive or borderline results were subsequently examined through both a recombinant immunofluorescent assay and a plaque reduction neutralisation test (PRNT). FindingsSeroprevalence was 0{middle dot}97% (95% CI: 0{middle dot}72-1{middle dot}30) by ELISA and 0{middle dot}36% (95% CI: 0{middle dot}21-0{middle dot}61) by PRNT, and did not vary with either age or sex. All PRNT+ individuals reported having experienced at least one symptom (odds ratio (OR) of PRNT+ for each additional symptom: 1{middle dot}12 (95% CI: 1{middle dot}04-1{middle dot}21)). Apart from living in a household with a SARS-CoV-2 confirmed or suspected person, a recent history of reduced taste or smell, fever, chills/hot flashes, pain while breathing, pain in arms/legs, as well as muscle pain and weakness were significantly associated with the presence of neutralizing antibodies in those with mild to moderate infection (ORs 3{middle dot}44 to 9{middle dot}97, all p<0{middle dot}018). InterpretationOur findings indicate a relatively low SARS-CoV-2 seroprevalence in Bonn, Germany (until June 30th, 2020), with neutralizing antibodies detectable in only one third of those with a positive immunoassay result, implying that almost the entire population in this region remains susceptible to SARS-CoV-2 infection. FundingThe Rhineland Study is predominantly funded through the German Center for Neurodegenerative Diseases (DZNE) by the Federal Ministry of Education and Research (BMBF) and the Ministry of Culture and Science of the German State of North Rhine-Westphalia. The National Consultant Laboratory for Coronaviruses is funded by the Federal Ministry of Health (BMG). No additional funding was received for this seroprevalence study.