Guanidine treatment and impaired renal function in the Eaton-Lambert syndrome.
Authors: L D Blumhardt, A M Joekes, J Marshall, P E Philalithis
Journal: BMJ (1977)

<h3>Abstract</h3> <h3>Background</h3> The B.1.526 variant (WHO designation: Iota) is a SARS-CoV-2 variant of interest, as classified by both the US CDC and the WHO. Due to a lack of extensive genomic sequencing and contact tracing data, its key epidemiological properties have not been well characterized. <h3>Methods</h3> We utilized nine epidemiological and population datasets collected in New York City (NYC), where B.1.526 emerged, and comprehensive modeling to estimate the changes in transmissibility, immune escape potential, and infection fatality risk (IFR) for B.1.526. <h3>Findings</h3> Estimated transmission rate in the neighborhood where B.1.526 was initially detected was consistently higher than other neighborhoods in NYC and further increased during the weeks preceding B.1.526 detection, likely due to its early spread there. Overall, models estimated that B.1.526 had transmissibility about 15-25% higher than previously circulating variants and that it could escape immunity in 0-10% of previously infected persons. In addition, B.1.526 substantially increased IFR in older adults: by 46% (95% CI: 7.4 – 84%) among 45-64 year-olds, 82% (95% CI: 20 – 140%) among 65-74 year-olds, and 62% (95% CI: 45 – 80%) among 75+ during Nov 2020 – Apr 2021, compared to baseline IFR estimated for preexisting variants. <h3>Interpretation</h3> New variants like B.1.526 likely spread in the population weeks prior to detection, and partial immune escape (e.g., resistance to therapeutic antibodies) could offset prior medical advances and increase IFR. Early preparedness for and close monitoring of SARS-CoV-2 variants, their epidemiological characteristics, and disease severity are thus crucial to COVID-19 pandemic response as it remains a global public health threat. <h3>Research in context</h3> <h3>Evidence before this study</h3> We searched PubMed for studies published through June 23, 2021 on the B.1.526 (Iota) SARS-CoV-2 variant, using the terms “B.1.526”, “Iota variant” and “COVID-19”, or “Iota variant” and “SARS-CoV-2”. Our search returned 14 papers, from which we read the abstracts and identified 8 relevant studies. The majority (7 of 8) of these studies focused on identifying the specific mutations, namely L5F, T95I, D253G, additionally E484K or S477N for two different subclades (i.e., B.1.526-S:E484K and B.1.526-S:S477N) and a closely related subclade (i.e., B.1.526-S:L452R or B.1.526.1) as defined by spike mutations D80G, Δ144, F157S, L452R, T859N, and D950H; these studies also examined changes in neutralizing ability of convalescent plasma and vaccinee sera (mild reductions by ∼2-4 fold were reported) and changes in neutralizing ability of monoclonal antibodies (substantial reductions for some monoclonal antibodies were reported). Two studies used genomic data from GISAID to estimate the growth rate of B.1.526 during January - March 2021 and reported that it was similar to the Alpha variant (i.e., B.1.1.7), a SARS-CoV-2 variant of concern with around 50% higher transmissibility than preexisting variants. However, an epidemiological study using individual patient data from January 1 to April 5, 2021 reported no increases in secondary attack rate among contacts of B.1.526 cases, compared to non-VOC/VOI variants. This latter study also showed preliminary evidence that B.1.526 did not increase the risk of hospitalization or death, nor of vaccine breakthrough or reinfection. <h3>Added value of this study</h3> We utilized multiple datasets collected in New York City – where B.1.526 emerged – and model-inference methods to reconstruct the transmission dynamics, including the initial emergence of B.1.526 in the fall of 2020. We estimated that B.1.526 had a moderate increase (15-25%) in transmissibility and could escape immunity in 0-10% of previously infected individuals. In addition, B.1.526 substantially increased the infection-fatality risk (IFR) among adults 65 or older by &gt;60% during Nov 2020 – Apr 2021, compared to baseline risk estimated for preexisting variants. <h3>Implications of all the available evidence</h3> New SARS-CoV-2 variants like B.1.526 could increase transmissibility, evade prior immunity, and increase disease severity. Early preparedness for and close monitoring of SARS-CoV-2 variants and their epidemiological characteristics are crucial to COVID-19 pandemic response as it remains a global public health threat.