Fast-spreading U.K. virus variant raises alarms.
01 Jan 2021-Science (American Association for the Advancement of Science)-Vol. 371, Iss: 6524, pp 9-10
TL;DR: In 2019, the U.K. government announced that scientists had discovered a new variant of SARS-CoV-2 that appears to be spreading more rapidly and implemented stricter lockdown measures in London and southeast England to contain it.
Abstract: On 19 December 2020, the U.K. government announced that scientists had discovered a new variant of SARS-CoV-2 that appears to be spreading more rapidly and implemented stricter lockdown measures in London and southeast England to contain it. The lineage has apparently acquired 17 mutations that lead to amino acid changes in its proteins all at once, a feat never seen before in SARS-CoV-2. As this issue of Science went to press, scientists were still grappling to understand whether the variant really spreads faster, and if so, how. But its emergence drives home the notion that viral evolution could yet result in nasty surprises—just as the first effective vaccines are being rolled out.
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TL;DR: In this paper, Plante et al. examined SARS-CoV-2 variants including B.1.7 (UK), B. 1.351 (RSA), P.1,1.1 (Brazil), and B.429 (California).
262 citations
TL;DR: In this article, the authors showed that the South African variant B.1.351 was the most resistant to current monoclonal antibodies and convalescent plasma from coronavirus disease 2019 (COVID-19)-infected individuals.
159 citations
TL;DR: In this paper, the authors identify two groups of highly neutralizing nanobodies against SARS-CoV-2 variants, namely, group 1 and group 2, which is almost exclusively focused on the RBD-ACE2 interface and does not neutralize SARS CoV2 variants that carry E484K or N501Y substitutions.
Abstract: Since the start of the COVID-19 pandemic, SARS-CoV-2 has caused millions of deaths worldwide. Although a number of vaccines have been deployed, the continual evolution of the receptor-binding domain (RBD) of the virus has challenged their efficacy. In particular, the emerging variants B.1.1.7, B.1.351 and P.1 (first detected in the UK, South Africa and Brazil, respectively) have compromised the efficacy of sera from patients who have recovered from COVID-19 and immunotherapies that have received emergency use authorization1–3. One potential alternative to avert viral escape is the use of camelid VHHs (variable heavy chain domains of heavy chain antibody (also known as nanobodies)), which can recognize epitopes that are often inaccessible to conventional antibodies4. Here, we isolate anti-RBD nanobodies from llamas and from mice that we engineered to produce VHHs cloned from alpacas, dromedaries and Bactrian camels. We identified two groups of highly neutralizing nanobodies. Group 1 circumvents antigenic drift by recognizing an RBD region that is highly conserved in coronaviruses but rarely targeted by human antibodies. Group 2 is almost exclusively focused to the RBD–ACE2 interface and does not neutralize SARS-CoV-2 variants that carry E484K or N501Y substitutions. However, nanobodies in group 2 retain full neutralization activity against these variants when expressed as homotrimers, and—to our knowledge—rival the most potent antibodies against SARS-CoV-2 that have been produced to date. These findings suggest that multivalent nanobodies overcome SARS-CoV-2 mutations through two separate mechanisms: enhanced avidity for the ACE2-binding domain and recognition of conserved epitopes that are largely inaccessible to human antibodies. Therefore, although new SARS-CoV-2 mutants will continue to emerge, nanobodies represent promising tools to prevent COVID-19 mortality when vaccines are compromised. Multivalent nanobodies against SARS-CoV-2 from mice engineered to produce camelid nanobodies recognize conserved epitopes that are inaccessible to human antibodies and show promise as a strategy for dealing with viral escape mutations.
122 citations
TL;DR: In this paper, the S1 subunit was removed from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and developed stabilized stem (SS) antigens.
44 citations
Imperial College London1, Institut Gustave Roussy2, Guy's and St Thomas' NHS Foundation Trust3, Université libre de Bruxelles4, Cardiff University5, Barts Health NHS Trust6, Hebron University7, University of Genoa8, University of Barcelona9, University of Trieste10, University of Pavia11, King's College London12, Ludwig Maximilian University of Munich13, Università Campus Bio-Medico14, University College London15, University of L'Aquila16, Marche Polytechnic University17, Humanitas University18, University of Vic19
TL;DR: In this article, the severity and mortality from COVID-19 among patients with cancer have improved during the course of the SARS-CoV-2 pandemic in Europe.
Abstract: Importance: Whether the severity and mortality of COVID-19 in patients with cancer have improved in terms of disease management and capacity is yet to be defined. Objective: To test whether severity and mortality from COVID-19 among patients with cancer have improved during the course of the pandemic. Design, Setting, and Participants: OnCovid is a European registry that collects data on consecutive patients with solid or hematologic cancer and COVID-19. This multicenter case series study included real-world data from 35 institutions across 6 countries (UK, Italy, Spain, France, Belgium, and Germany). This update included patients diagnosed between February 27, 2020, and February, 14, 2021. Inclusion criteria were confirmed diagnosis of SARS-CoV-2 infection and a history of solid or hematologic cancer. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: Deaths were differentiated at 14 days and 3 months as the 2 landmark end points. Patient characteristics and outcomes were compared by stratifying patients across 5 phases (February to March 2020, April to June 2020, July to September 2020, October to December 2020, and January to February 2021) and across 2 major outbreaks (February to June 2020 and July 2020 to February 2021). Results: At data cutoff, 2795 consecutive patients were included, with 2634 patients eligible for analysis (median [IQR] age, 68 [18-77] years ; 52.8% men). Eligible patients demonstrated significant time-dependent improvement in 14-day case-fatality rate (CFR) with estimates of 29.8% (95% CI, 0.26-0.33) for February to March 2020; 20.3% (95% CI, 0.17-0.23) for April to June 2020; 12.5% (95% CI, 0.06-22.90) for July to September 2020; 17.2% (95% CI, 0.15-0.21) for October to December 2020; and 14.5% (95% CI, 0.09-0.21) for January to February 2021 (all P < .001) across the predefined phases. Compared with the second major outbreak, patients diagnosed in the first outbreak were more likely to be 65 years or older (974 of 1626 [60.3%] vs 564 of 1008 [56.1%]; P = .03), have at least 2 comorbidities (793 of 1626 [48.8%] vs 427 of 1008 [42.4%]; P = .001), and have advanced tumors (708 of 1626 [46.4%] vs 536 of 1008 [56.1%]; P < .001). Complications of COVID-19 were more likely to be seen (738 of 1626 [45.4%] vs 342 of 1008 [33.9%]; P < .001) and require hospitalization (969 of 1626 [59.8%] vs 418 of 1008 [42.1%]; P < .001) and anti-COVID-19 therapy (1004 of 1626 [61.7%] vs 501 of 1008 [49.7%]; P < .001) during the first major outbreak. The 14-day CFRs for the first and second major outbreaks were 25.6% (95% CI, 0.23-0.28) vs 16.2% (95% CI, 0.13-0.19; P < .001), respectively. After adjusting for country, sex, age, comorbidities, tumor stage and status, anti-COVID-19 and anticancer therapy, and COVID-19 complications, patients diagnosed in the first outbreak had an increased risk of death at 14 days (hazard ratio [HR], 1.85; 95% CI, 1.47-2.32) and 3 months (HR, 1.28; 95% CI, 1.08-1.51) compared with those diagnosed in the second outbreak. Conclusions and Relevance: The findings of this registry-based study suggest that mortality in patients with cancer diagnosed with COVID-19 has improved in Europe; this improvement may be associated with earlier diagnosis, improved management, and dynamic changes in community transmission over time.
43 citations