The Daily Top 10

COVID Reference’s daily Top 10 presents the best papers published in the best medical and scientific journals. Daily means daily: Monday, Tuesday, Wednesday, Thursday, Friday, Saturday and even Sunday. Never miss a day!

 

20 October

Genetics

Severe Covid-19 GWAS Group, Ellinghaus D, Degenhardt F, et al. Genomewide Association Study of Severe Covid-19 with Respiratory Failure. N Engl J Med. 2020 Oct 15;383(16):1522-1534. PubMed: https://pubmed.gov/32558485. Full-text: https://doi.org/10.1056/NEJMoa2020283

Only a small proportion of patients with SARS-CoV-2 infection have respiratory compromise, a respiratory distress syndrome, and multiorgan failure. Who is to blame, the virus or the host? To help answer this question, Andre Franke, Tom Karlsen and 404 colleagues, on behalf of The Severe Covid-19 GWAS Group, conducted a genomewide association study involving patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe: 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain. The group identified associations between the risk of severe Covid-19 and a multigene locus at 3p21.31 and the ABO blood group locus at 9q34.2. The HLA region did not show any association signal.

See also the comment by Kaser A. Genetic Risk of Severe Covid-19. N Engl J Med. 2020 Oct 15;383(16):1590-1591. PubMed: https://pubmed.gov/33053291. Full-text: https://doi.org/10.1056/NEJMe2025501. The preliminary response to our initial question:  The determinants of disease severity appear to reside almost exclusively in host factors, not in viral genetic variation.

Figure 2. GWAS Summary (Manhattan) Plot of the Meta-analysis Association Statistics Highlighting Two Susceptibility Loci with Genomewide Significance for Severe Covid-19 with Respiratory Failure. | Shown is a Manhattan plot of the association statistics from the main meta-analysis (controlled for potential population stratification). The red dashed line indicates the genomewide significance threshold of a P value less than 5×10−8. Reproduced with permission.

 

Virology

Rattanapisit K, Shanmugaraj B, Manopwisedjaroen S. et al. Rapid production of SARS-CoV-2 receptor binding domain (RBD) and spike specific monoclonal antibody CR3022 in Nicotiana benthamiana. Sci Rep 10, 17698 (2020). Full-text: https://doi.org/10.1038/s41598-020-74904-1

This study demonstrates the rapid production of the RBD of SARS-CoV-2 and mAb CR3022 in Nicotiana benthamiana using a transient expression system. The plant-produced RBD showed specific binding to the receptor of SARS-CoV-2 (ACE2), confirming its structural integrity. Further, the plant-produced mAb CR3022 exhibited binding to SARS-CoV-2, but it failed to neutralize the virus in vitro. Overall, this study provides a proof-of-principle for the rapid production of SARS-CoV-2 antigens or monoclonal antibodies in a plant expression system in order to produce diagnostic reagents, vaccines and therapeutics.

 

Transmission

Richmond CS, Sabin AP, Jobe DA, et al. SARS-CoV-2 sequencing reveals rapid transmission from college student clusters resulting in morbidity and deaths in vulnerable populations. medRxiv 2020, posted 14 October. Full-text: https://doi.org/10.1101/2020.10.12.20210294

The title says it all: a substantial SARS-CoV-2 outbreak coincided with the return to in-person instruction at three local academic institutions. From 111 sequenced genomes the authors identified rapid transmission of the virus into more vulnerable populations. One of the variants made its way into two care homes, infecting 8 residents. Two died. MedRxiv article – not yet peer reviewed.

 

Prevention

Lauterbach K. Will Germany’s effective Covid strategy work again as it enters a second wave? The Guardian 2020, published 19 October. Full-text: https://www.theguardian.com/commentisfree/2020/oct/19/germany-covid-second-wave-virus

The first wave taught us that if politicians and scientists work together, they have more chance of beating this virus.

 

Immunology

Dong J, Huang B, Wang B, et al. Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2. Sci Rep 10, 17806 (2020). Full-text: https://doi.org/10.1038/s41598-020-74761-y

Llamas against SARS-CoV2? In May, Djambo Dong et al. identified humanized VHHs that bind to S protein and block the S/ACE2 interaction (see article below; a VHH antibody [or nanobody] is the antigen binding fragment of heavy chain only antibodies). Now the authors used computer-aided design to construct multi-specific VHH antibodies fused to human IgG1 Fc. The resulting tri-specific VHH-Fc antibodies show potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization.

Dong J, Huang B, Jia Z, et al. Development of multi-specific humanized llama antibodies blocking SARS-CoV-2/ACE2 interaction with high affinity and avidity. Emerg Microbes Infect. 2020 Dec;9(1):1034-1036. PubMed: https://pubmed.gov/32403995. Full-text: https://doi.org/10.1080/22221751.2020.1768806

 

Schwarzkopf S, Krawczyk A, Knop D, Klump H, Heinold A, Heinemann FM, et al. Cellular immunity in COVID-19 convalescents with PCR-confirmed infection but with undetectable SARS-CoV-2–specific IgG. Emerg Infect Dis. 2021 Jan. Full-text: https://wwwnc.cdc.gov/eid/article/27/1/20-3772_article

Sina Schwarzkopf and colleagues from Essen University (Germany) have investigated immune responses among a group of convalescent, potential blood donors in Germany who had PCR-confirmed SARS-CoV-2 infection. Sixty days after onset of symptoms, 13/78 (17%) study participants had borderline or negative results to an ELISA detecting IgG against the S1 protein.  Cellular immunity toward any of the SARS-CoV-2 antigens was detectable in 7/9 (78%) participants who had a low antibody ratio <1.

 

Clinical

Yang W, Kandula S, Huynh M, et al. Estimating the infection-fatality risk of SARS-CoV-2 in New York City during the spring 2020 pandemic wave: a model-based analysis. Lancet Infect Dis 2020, published 19 October. Full-text: https://doi.org/10.1016/S1473-3099(20)30769-6

The infection-fatality risk (IFR) is the risk of death among all infected individuals including those with asymptomatic and mild infections. Here, Wan Yang and colleagues report the outcome of the SARS-CoV-2 infection during the first epidemic wave in in New York City. They found an overall IFR of 1.39%. Age was the all-important factor: 25–44 years: 0.11%; 45–64 years: 0.94%; 65-74 years: 4.9%; 75 years and older: 14.2%. The sample size reported y the authors is impressive: 205 639 people with laboratory-confirmed SARS-CoV-2 infection 2 and 21 447 confirmed and probable COVID-19-related deaths.

 

Severe COVID

Leiter RE. Reentry. N Engl J Med. 2020 Oct 14. PubMed: https://pubmed.gov/33053276. Full-text: https://doi.org/10.1056/NEJMp2027447

“While we try to heal from the collective trauma we experienced in our hospital over the worst 4 months of the local epidemic, I struggle to know where to look. Peering into the future, given what we see on the news, saturates me with dread. And yet it’s too early to look back. Perspective can’t develop in the presence of open wounds.”

 

Potential Drugs

El-Hachem N, Eid E, Nemer G, et al. Integrative transcriptome analyses empower the anti-COVID-19 drug arsenal. ISCIENCE (2020). Full-text: https://doi.org/10.1016/j.isci.2020.101697

Searching for potential therapeutic targets, the authors used integrative data-driven computational analyses on large transcriptomic datasets encompassing both in vitro and in vivo SARS-CoV-2 infected samples as well as normal human lung biopsy samples. They provide a repertoire of drug repurposing candidates, identidy TNF-NFkB signaling as a targetable hallmark for COVID-19 and suggest BTK inhibitors as repurposable candidates for COVID-19.

 

Society, Prevention

The Editors. Why Nature supports Joe Biden for US president. Nature 2020, published on 14 October. Full-text: https://www.nature.com/articles/d41586-020-02852-x

“We cannot stand by and let science be undermined. Joe Biden’s trust in truth, evidence, science and democracy make him the only choice in the US election.”

 

Spanish

If you read Spanish, read de Miguel R. El Reino Unido da luz verde a un ensayo que infectará con el coronavirus a personas sanas. El País 2020, published 20 October. Full-text: https://elpais.com/ciencia/2020-10-20/el-reino-unido-da-luz-verde-a-un-ensayo-que-infectara-con-el-coronavirus-a-personas-sanas.html

El llamado Desafío Humano permite acelerar la comprobación de la eficacia de las vacunas. Algunos científicos cuestionan la utilidad del método.

 

French

If you read French, read Mesmer P, Pons P. Lutte contre le Covid-19: les leçons sud-coréenne et japonaise. Le Monde 2020, published 19 October. Full-text: https://www.lemonde.fr/idees/article/2020/10/19/lutte-contre-le-covid-19-les-lecons-sud-coreenne-et-japonaise_6056519_3232.html

La Corée du Sud et le Japon ont été relativement épargnés par le Covid-19 et ignorent la déconnexion entre pouvoir et population. Respect de l’hygiène et responsabilité collective s’y enseignent dès l’école.

 

Deutsch

If you read German, read Köppe  J. Wie tödlich ist Covid-19? Der Spiegel 2020, published 20 October. Full-text: https://www.spiegel.de/wissenschaft/medizin/corona-diskussion-ueber-studie-der-weltgesundheitsorganisation-wie-toedlich-ist-covid-19-wirklich-a-9d05b174-87fd-44e4-a1a3-da9760fad1d5

Eine Studie der WHO hat Verwirrung gestiftet: Ist die Sterblichkeit bei Corona-Infizierten viel niedriger als angenommen? Ein genauerer Blick auf die Zahlen offenbart ein Missverständnis.

 

Roth J. “Viele haben geweint”. Die Zeit 2020, published 20 October. Full-text: https://www.zeit.de/politik/ausland/2020-10/ngo-facing-hunger-west-virginia-armut-cynthia-kirkhart-usa-lebensmittelverteilung

Corona hat viele Amerikaner so arm gemacht, dass sie kein Geld mehr fürs Essen haben. Zu Besuch bei einer Hilfsorganisation, die in West Virginia gegen den Hunger kämpft.

 

See also the previous Top 10 papers: https://covidreference.com/top10.

 

By Christian Hoffmann &
Bernd S. Kamps

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