Copy-editor: Rob Camp
Paper of the Day
Shen X, Tang H, McDanal C, et al. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines. Cell Host Microbe March 03, 2021. https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(21)00102-5
Good news. Using a lentivirus-based pseudovirus assay, Xiaoying Shen and colleagues from Duke, Durham, US, show that B.1.1.7 is probably not a neutralization escape variant of concern for COVID-19 vaccines. Moreover, B.1.1.7 is unlikely to increase the risk of SARS-CoV-2 re-infection.
Wibmer CK, Ayres F, Hermanus T, et al. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. Nature Medicine 02 March 2021. https://www.nature.com/articles/s41591-021-01285-x
B.1.351 is a bigger problem. This study (for months available as a pre-print only, now as a beautiful paper in Nature Medicine) shows that this lineage completely escapes three classes of therapeutically relevant antibodies. The B.1.351 pseudovirus also exhibited substantial to complete escape from neutralization, but not binding, by convalescent plasma. The overwhelming majority of monoclonal antibodies already on the path to licensure target residues K417 or E484 and are therefore likely to be futile against this variant.
Schroeder S, Pott F, Niemeyer D, et al. Interferon antagonism by SARS-CoV-2: a functional study using reverse genetics. Lancet Microbe March 04, 2021. https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00027-6/fulltext
Do differences in receptor usage determine all the differences in disease presentation between SARS-CoV and SARS-CoV-2? This work by Christian Drosten and colleagues shows that SARS-CoV-2 suppresses cytokine induction and interferon signaling with lower efficiency than SARS-CoV, despite the shared genome architecture and expression of homologous viral proteins. Gene encoding protein 6 as a genetic marker of virulence varied between SARS-CoV and SARS-CoV-2, thus providing a target for genome-based surveillance of circulating strains of SARS-CoV-2. The authors recommend to monitor sequence evolution of SARS-CoV ORF6.
Bost P, De Sanctis F, Canè S et al. Deciphering the state of immune silence in fatal COVID-19 patients. Nat Commun March 4, 2021 12, 1428. https://www.nature.com/articles/s41467-021-21702-6#citeas
This study shows innate and adaptive immune dysfunction, including loss of immune suppression by blood myeloid cells and the replacement of lung memory CD8+ T cells by naive T cells, suggesting a state of “immune silence” that correlates with a severe clinical manifestation and fatal outcome.
Azzolini C, Donati S, Premi E, et al. SARS-CoV-2 on Ocular Surfaces in a Cohort of Patients With COVID-19 From the Lombardy Region, Italy. JAMA Ophthalmology March 4, 2021. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2777178
SARS-CoV-2 was present on the ocular surface in 52 of 91 COVID-19 patients, showing a wide variability in the viral load. Some had positive conjunctival swabs while having a negative nasopharyngeal swab. However, the authors did not determine the infectivity of the viral material detected. Clinical relevance remains unclear.
Moshe M, Daunt A, Flower B, et al. SARS-CoV-2 lateral flow assays for possible use in national covid-19 seroprevalence surveys (React 2): diagnostic accuracy study. BMJ. 2021 Mar 2;372:n423. PubMed: https://pubmed.gov/33653694 . Full-text: https://doi.org/10.1136/bmj.n423
In contrast to routine serology assays, the use of lateral flow immunoassays (LFIAs) does not require the support of central laboratories and offers a rapid and affordable method of testing. This study shows that LFIA sensitivity is variable on serum and finger prick testing, and often differs from that stated by the manufacturer. Specificity of all LFIAs was high. However, none showed sufficient sensitivity and specificity to be considered for routine clinical use. One further LFIA (Surescreen) was identified as suitable for use in seroprevalence studies because it showed comparable performance to the LFIA currently used in the React 2 seroprevalence studies (Fortress). However, the performance of Surescreen was not significantly better than Fortress.
Martinez MW, Tucker AM, Bloom J, et al. Prevalence of Inflammatory Heart Disease Among Professional Athletes With Prior COVID-19 Infection Who Received Systematic Return-to-Play Cardiac Screening. JAMA Cardiol March 4 2021; https://jamanetwork.com/journals/jamacardiology/fullarticle/2777308
“The virus challenged me and I defeated it.” That’s what Zlatan Ibrahimovic, famous Swedish soccer player who caught COVID-19 last September, posted on Instagram (you don’t know him? Then please take 94 seconds: https://www.youtube.com/watch?v=GcCVfNA7otY).
“But you are not Zlatan. Do not challenge the virus. Use your head, respect the rules. Social distancing and masks, always. We will win.”
Zlatan was right! But should we have been worried about him? Probably not. In this multicenter, retrospective cross-sectional study of RTP cardiac testing performed on 789 professional athletes with COVID-19 (58% symptomatic, 42% asymptomatic or pauci-symptomatic), imaging evidence of inflammatory heart disease (performed around 3 weeks after positive testing) that resulted in restriction from play was identified in 5 athletes (0.6%) only. No adverse cardiac events occurred in the athletes who underwent cardiac screening and resumed professional sport participation. Thus, with regard to mild COVID-19, there were many Zlatans. On the field, however, there is only one.
Bloom CI, Drake TM, Docherty AB, et al. Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19: a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK. Lancet Resp Med March 04, 2021. https://doi.org/10.1016/S2213-2600(21)00013-8
Analyzing 75,463 patients from the UK, Chloe Bloom and colleagues show that patients with chronic pulmonary disease had a high level of mortality, with a prevalence of 40% for in-hospital death. Of patients with asthma, only those with severe asthma had increased mortality compared to those without an underlying respiratory condition. Patients with asthma (aged ≥ 50 years) had a lower mortality risk if they had used inhaled corticosteroids within 2 weeks of admission.
López-Medina E, López P, Hurtado IC, et al. Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial. JAMA March 4, 2021; doi: 10.1001/jama.2021.3071. https://jamanetwork.com/journals/jama/fullarticle/2777389
The next hydroxychloroquine? Because of some evidence of activity in vitro, ivermectin has attracted huge interest. Several countries have included ivermectin in their treatment guidelines, leading to a surge in the demand for the drug by the general population and even alleged distribution of veterinary formulations. In this RCT that included 476 patients from Cali, Colombia, the duration of symptoms was not significantly different for patients who received either a 5-day course of ivermectin or placebo (median time to resolution of symptoms, 10 vs 12 days; hazard ratio for resolution of symptoms, 1.07). This is consistent with PK models showing that ivermectin levels do not reach the IC50 even for a dose level 10-times higher than the approved dose.
Lescure FX, Honda H, Fowler RA, et al. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Resp Med March 04, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00099-0/fulltext
This large placebo-controlled multinational Phase III trial evaluated two doses of sarilumab, an interleukin-6 receptor inhibitor, in 416 patients with severe or critical COVID-19. At day 29, no significant differences were seen between the arms. The authors bravely suggest several potential reasons for why sarilumab was not effective (IL-6 insufficient to quell the inflammatory phase of the disease, patient selection not based on inflammation markers, dosage too low, use of confounding concomitant steroids, etc). However, this strategy seems not be a game changer in this pandemic.
If you read French, read HerzbergN, Aeberhardt C. Covid-19 : comment la lutte contre les variants pourrait modifier les stratégies vaccinales. Le Monde 2021, published 25 February. Full-text : https://www.lemonde.fr/planete/article/2021/02/25/covid-19-la-lutte-contre-les-variants-s-organise_6071122_3244.html
L’apparition de nouvelles mutations du virus contraint les laboratoires à adapter leurs vaccins, les agences sanitaires à inventer de nouvelles procédures réglementaires, et les Etats à réexaminer leur stratégie vaccinale.
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