Copy-editor: Rob Camp
Paper of the Day
Amanat F, Thapa M, Lei T, et al. The plasmablast response to SARS-CoV-2 mRNA vaccination is dominated by non-neutralizing antibodies that target both the NTD and the RBD. medRxiv 2021, posted 9 March. Full-text: https://doi.org/10.1101/2021.03.07.21253098
Florian Krammer, Fatima Amanat and colleagues studied the plasmablast response to SARS-CoV-2 mRNA-based vaccination. The authors demonstrate that the antibody responses to SARS-CoV-2 mRNA vaccination comprise a large proportion of non-neutralizing antibodies and are co-dominated by NTD and RBD antibodies. The NTD portion of the spike represents, therefore, an important vaccine target. Since all viral variants of concern are heavily mutated in this region, these observations warrant further attention to optimize SARS-CoV-2 vaccines. Finally, broadly cross-reactive mAbs to β-coronavirus spike proteins are induced after vaccination and suggest a potential development path for a pan-β-coronavirus vaccine.
Ellebedy A, Turner J, O’halloran J, et al. SARS-CoV-2 mRNA vaccines induce a robust germinal centre reaction in humans. Research Square 2021, posted 9 March. Full-text: https://doi.org/10.21203/rs.3.rs-310773/v1
Did you feel that your arm is on “fire” after getting your SARS-CoV-2 mRNA vaccine? Did you get some fine needle aspirates of your draining axillary lymph nodes? You could have investigated the dynamics of antibody secreting plasmablasts (PBs) and germinal center (GC) B cells induced by these vaccines in SARS-CoV-2 naïve and antigen-experienced humans. Ellebedy et al did just that. They demonstrated that SARS-CoV-2 mRNA-based vaccination of humans induces a robust and persistent GC B cell response that engages pre-existing as well as new B cell clones. High-affinity, broad, and durable humoral immunity on the horizon?
Muecksch F, Weisblum Y, Barnes CO, et al. Development of potency, breadth and resilience to viral escape mutations in SARS-CoV-2 neutralizing antibodies. bioRxiv 2021, posted 8 March. Full-text: https://doi.org/10.1101/2021.03.07.434227
Might affinity maturation generate antibodies that are resilient to viral evolution? Paul Bieniasz, Frauke Muecksch and colleagues think so. After analyzing six independent antibody lineages, they found that for certain ones, maturation enabled neutralization of circulating SARS-CoV-2 variants of concern and heterologous sarbecoviruses. The authors conclude that increasing antibody diversity through prolonged or repeated antigen exposure may improve protection against diversifying SARS-CoV-2 populations, and perhaps against other pandemic threat coronaviruses.
CMMID 202103. European COVID-19 Forecast hub. London School of Hygiene & Tropical Medicine and ECDC 2021. Website: https://covid19forecasthub.eu
The European COVID-19 Forecast hub aims to collate and meaningfully combine short-term forecasts of COVID-19 from across Europe in order to 1) improve situational awareness and 2) quantify the current trajectory of COVID-19 everywhere whilst acknowledging uncertainty.
Mallapaty S. The search for animals harbouring coronavirus — and why it matters. Nature 2021, published 2 March. Full-text: https://www.nature.com/articles/d41586-021-00531-z
Monitoring pets, livestock and wildlife to see where SARS-CoV-2 could hide, and whether it might resurge.
Hensley MK, Bain WG, Jacobs J, et al. Intractable Coronavirus Disease 2019 (COVID-19) and Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Replication in a Chimeric Antigen Receptor-Modified T-Cell Therapy Recipient: A Case Study. Clin Infect Dis 2021. Full-text: https://doi.org/10.1093/cid/ciab072
Prolonged transmission from immunosuppressed patients is possible. A chimeric antigen receptor-modified T cell therapy recipient developed severe coronavirus disease 2019, intractable RNAemia, and viral replication lasting > 2 months. Deep sequencing revealed multiple sequence variants consistent with intra-host viral evolution.
Braun KM, Moreno GK, Halfmann PJ, et al. Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck. PLOS Pathogens 2021, published 26 February. Full-text: https://doi.org/10.1371/journal.ppat.1009373
How is genetic variation generated and selected within and between individual hosts? Using domestic cats as a model, Thomas Friedrich, Katarina Braun and colleagues show that within-host SARS-CoV-2 genetic variation is predominantly influenced by genetic drift and purifying selection. In particular, they identified a notable variant at amino acid position 655 in spike (H655Y), which was previously shown to confer escape from human monoclonal antibodies. This variant arises rapidly and persists at intermediate frequencies in index cats.
Grint DJ, Wing K, Williamson E, et al. Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England. MedRxiv 2021, posted 8 March. Full-text: https://doi.org/10.1101/2021.03.04.21252528
The authors draw data from a research platform that covers 40% of England’s population registered with a general practitioner. B.1.1.7 status was known for 184,786 people. The B.1.1.7 group was younger with a lower proportion of older cases (80+: 0.9% VOC vs. 1.6% non-B.1.1.7 cases), with fewer co-morbidities (2+ co-morbidities: 2.9% vs. 3.8%). After controlling for co-morbidities, age, week, region & other sociodemographics, the authors found an increased risk of death for B.1.1.7 compared with non-B.1.1.7 cases (HR: 1.67; 95% CI: 1.34 – 2.09; P < 0.0001).
Tablizo FA, Kim KM, Lapid CM, et al. Genome sequencing and analysis of an emergent SARS-CoV-2 variant characterized by multiple spike protein mutations detected from the Central Visayas Region of the Philippines. medRxiv 2021, posted 6 March. Full-text: https://doi.org/10.1101/2021.03.03.21252812
The authors describe the emergence of a new SARS-CoV-2 lineage, mainly from the Central Visayas region of the Philippines: 13 lineage-defining mutations, including the co-occurrence of the E484K, N501Y, and P681H mutations at the spike protein region, as well as three additional radical amino acid replacements towards the C-terminal end of the said protein. A three amino acid deletion at positions 141 to 143 (LGV141_143del) in the spike protein is reminiscent of a region preceding the 144Y deletion found in the B.1.1.7 variant. See also the ‘P.3’ proposition by Andrew Rambaut: https://github.com/cov-lineages/pango-designation/issues/27.
Shah A, Gribben C, Bishop J, et al. Effect of vaccination on transmission of COVID-19: an observational study in healthcare workers and their households. GitHub preprint, posted 12 March. Full-text: https://github.com/ChronicDiseaseEpi/hcw/blob/master/vaccine_manuscript.pdf
Household members of vaccinated healthcare workers have a lower risk for being infected with SARS-CoV-2 (rate per 100 person-years 9∙40 versus 5∙93; HR 0∙70, 95% CI: 0∙63 to 0∙78). This is the result of a Scottish cohort comprised of 194,362 household members (mean age 31∙1 ± 20∙9 years) and 144,525 healthcare workers (mean age 44∙4 ± 11∙4 years). As household members of healthcare workers can also be infected by other people, this 30% risk reduction is probably an underestimate of the effect vaccination will have on transmission of SARS-CoV-2.
Fischer R, van Doremalen N, Adney D, et al. ChAdOx1 nCoV-19 (AZD1222) protects against SARS-CoV-2 B.1.351 and B.1.1.7. bioRxiv 2021, posted 11 March. Full-text: https://doi.org/10.1101/2021.03.11.435000
Thinking of maybe not getting the vaccine because of the new variants? Think again! Here, Robert Fischer, Neeltje van Doremalen and colleagues show a lack of disease in Syrian hamsters vaccinated with the AstraZeneca vaccine when infected with B.1.1.7 or B.1.351 (first detected in the UK and South Africa, respectively). The authors observed a 9.5-fold reduction of virus-neutralizing antibody titer in vaccinated hamster sera against B.1.351 compared to B.1.1.7. Vaccinated hamsters challenged with B.1.1.7 or B.1.351 did not lose weight compared to control animals. Interesting data from a pre-print paper that need to be confirmed in clinical vaccine practice.
Public Health England 20210222. PHE monitoring of the early impact and effectiveness of COVID-19 vaccination in England. UK Government 2021, 22 February; accessed 5 March 2021. Full-text: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/963532/COVID-19_vaccine_effectiveness_surveillance_report_February_2021_FINAL.pdf
Public Health England reports on 11,860 confirmed cases of COVID in those aged over 80 years. The Pfizer-BioNTech vaccine effectiveness was 57% (95% CI: 48-63%) from 28 days after the first dose of vaccination. In 8119 individuals aged over 80 years with a confirmed PCR positive test and followed for at least 21 days, the case fatality ratio was lower in cases vaccinated at least 14 days before onset than in unvaccinated cases. This would indicate that within vaccinated individuals who do become symptomatic the vaccine confers additional protection against death.
Ghebreyesus TA. A ‘me first’ approach to vaccination won’t defeat Covid. The Guardian 2021, published 5 March. Full-text: https://www.theguardian.com/commentisfree/2021/mar/05/vaccination-covid-vaccines-rich-nations
Of the 225m vaccines administered so far, most have been in a handful of rich nations. This has to change, for all our sakes, says Tedros Adhanom Ghebreyesus, director general of WHO. The normal rules of business that protect the profits of vaccine manufacturers will have to be set aside if that is what it takes to ensure everybody is immunized against SARS-CoV-2. See also Boseley S. WHO chief: waive Covid vaccine patents to put world on ‘war footing’ . The Guardian 2021, published 5 March. Full-text: https://www.theguardian.com/world/2021/mar/05/covid-vaccines-who-chief-backs-patent-waiver-to-boost-production
Boseley S, Brooks L. UK will diverge from EU and US on approving tweaked Covid vaccines. The Guardian 2021, published 4 March. Full-text: https://www.theguardian.com/society/2021/mar/04/vaccines-tweaked-for-covid-variants-will-be-fast-tracked-safely-says-uk-regulator
The UK will adopt a different standard from Europe and the US when it considers approval for coronavirus vaccines that have been tweaked to deal with variants, the UK regulator has said.
Wohlfahrt J, Fonager J, Albertsen M, et al. Increased Risk of Hospitalisation Associated with Infection with SARS-CoV-2 Lineage B.1.1.7 in Denmark. Lancet Preprints 2021, posted 2 March. Full-text: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3792894
Infection with B.1.1.7 was associated with an increased risk of hospitalization compared with other lineages (adjusted odds ratio: 1.64).