Top 10: October 10

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By Christian Hoffmann &
Bernd S. Kamps

 

This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing the text to give it early visibility.

10 October

Virology

Bruchez A, Sha K, Johnson J, et al. MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses. Science 2020, published 9 October. Full-text: https://doi.org/10.1126/science.abb3753

The concerted efforts of antiviral factors within cells are central to host cell defense. Without these factors, the cell remains defenseless against potentially harmful pathogens (Wells 2020). Here, the authors show that the major histocompatibility complex (MHC) class II transactivator (CIITA) has antiviral activity against Ebola virus (EBOV). They show that CIITA induces resistance by up-regulation of the p41 isoform of CD74, which blocks cathepsin-mediated cleavage of viral GPs, thereby preventing viral fusion. CD74 p41 can also block the endosomal entry pathway of coronaviruses, including SARS-CoV-2.

See also the comment by Wells, AI, Coyne CB. Inhibiting Ebola virus and SARS-CoV-2 entry. Science 2020, published 9 October. Full-text: https://doi.org/10.1126/science.abe2977

 

Epidemiology

Rader B, Scarpino SV, Nande A, et al. Crowding and the shape of COVID-19 epidemics. Nat Med 2020, published 5 October. Full-text: https://doi.org/10.1038/s41591-020-1104-0

The dynamic of the current SARS epidemics in the Greater Paris and Madrid are reason for concern. In this article, Moritz Kraemer, Benjamin Rader and colleagues predict that crowded cities worldwide could experience more prolonged epidemics. The 2020/2021 autumn and winter season will be a hard time.

 

Oster AM, Caruso E, DeVies J, Hartnett KP, Boehmer TK. Transmission Dynamics by Age Group in COVID-19 Hotspot Counties — United States, April–September 2020. MMWR Morb Mortal Wkly Rep. ePub: 9 October 2020. Fulltext: http://dx.doi.org/10.15585/mmwr.mm6941e1

Understanding whether increasing incidence is predominantly occurring in specific age groups is important for identifying opportunities to prevent or reduce transmission. Here the authors analyze hotspot counties, particularly those in the US South and West. The positivity rate increased earliest in younger persons (18-24 years), followed by several weeks of increasing percent positivity among older age groups.

 

Transmission

Wilson RF, Sharma AJ, Schluechtermann S, et al. Factors Influencing Risk for COVID-19 Exposure Among Young Adults Aged 18–23 Years — Winnebago County, Wisconsin, March–July 2020. MMWR Morb Mortal Wkly Rep. ePub: 9 October 2020. DOI: http://dx.doi.org/10.15585/mmwr.mm6941e2

Still in the US: Which are the drivers of behaviors that might influence risk for COVID-19 exposure among young adults? In a remote US County, these were low severity of disease outcome; peer pressure; and exposure to misinformation, conflicting messages, or opposing views regarding masks. A scientifically inspired national prevention policy would have been helpful.

 

Prevention

Eden E, Frencken J, Gao S, et al. Managing dental caries against the backdrop of COVID-19: approaches to reduce aerosol generation. Br Dent J 229, 411–416 (2020). https://doi.org/10.1038/s41415-020-2153-y

SARS-CoV-2 can be transmitted via aerosols – a particular concern for dentists you use need to perform procedures that produce aerosol. Ece Eden et al. aim to remove or reduce the generation of aerosols during the management of carious lesions (use of high-viscosity glass-ionomer sealants, atraumatic restorative treatment, silver diamine fluoride, the Hall Technique and resin infiltration). May we give you a personal advice? If you have problem with your teeth, fix them now! In a few weeks, it may be more difficult or less safe to get dental care.

 

Pathogenesis

Zizzo  G, Cohen PL. Imperfect storm: is interleukin-33 the Achilles heel of COVID-19? Lancet Rheumatol 2020, published 9 October Full-text: https://doi.org/10.1016/S2665-9913(20)30340-4

Could interleukin (IL)-33 be the great director of the COVID Pathogenesis Orchestra, driving all stages of disease (i.e., asymptomatic, mild–moderate, severe–critical, and chronic–fibrotic)? That’s the hypothesis developed by Gaetano Zizzo and Philip Cohen. You will need time to plough through the paper (9 pages, 101 references).

 

Treatment

Baum A, Ajithdoss D, Copin R, et al. REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters. Science 2020, published 9 October. Full-txt: https://doi.org/10.1126/science.abe2402

The authors evaluate REGN-COV2, a cocktail of two neutralizing antibodies (REGN10987+REGN10933) targeting non-overlapping epitopes on the SARS-CoV-2 spike protein, in rhesus macaques and golden hamsters. REGN-COV-2 can reduce virus load and decrease virus-induced pathological sequalae in rhesus macaques. In hamsters, the cocktail limited weight loss and evidence of pneumonia in the lungs. It is too early to predict the clinical usefulness of this cocktail in COVID-19 patients. It is currently being tested in clinical trials.

 

Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 – Final Report. N Engl J Med. 2020 Oct 8:NEJMoa2007764. PubMed: https://pubmed.gov/32445440. Full-text: https://doi.org/10.1056/NEJMoa2007764

The final report of a preliminary report (see our May 23 Top 10) of a (promotional?) presentation at the White House almost 6 months ago. The paper confirms that of a total of 1062 patients, those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo. John Beigel et al. also confirm that remdesivir had no statistically significant impact on mortality. Dexamethasone holds more promise than remdesivir: The RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report. NEJM July 17, 2020. Full-text: https://doi.org/10.1056/NEJMoa2021436 (see also our July 18 comment).

 

No Treatment

RECOVERY Collaborative Group, Horby P, Mafham M, et al. Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med. 2020 Oct 8. PubMed: https://pubmed.gov/33031652. Full-text: https://doi.org/10.1056/NEJMoa2022926

If you are still interested in hydroxychloroquine (most clinicians are not), see here the results of a randomized trial by the RECOVERY Collaborative Group. The conclusion: among hospitalized patients, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care.

 

Severe COVID

Avilés-Jurado FX, Prieto-Alhambra D, González-Sánchez N, et al. Timing, Complications, and Safety of Tracheotomy in Critically Ill Patients With COVID-19. JAMA Otolaryngol Head Neck Surg. Published online October 08, 2020. Full-text: http://doi.org/10.1001/jamaoto.2020.3641

How safe is an early bedside surgical tracheotomy in patients with coronavirus disease 2019 (COVID-19)? The authors analyze data from 50 patients (mean [SD] age, 63.8 [9.2] years; 33 [66%] male). The median time from intubation to tracheotomy was 9 days (interquartile range, 2-24 days). The successful weaning rate was higher in the early tracheotomy group than in the late tracheotomy group (adjusted hazard ratio, 2.55), but the difference was not statistically significant. There was no infection among surgeons within 4 weeks after the last tracheotomy.

 




Spanish

If you read Spanish, read Saldaña C, Mouzo J. “Están primando más la política que la salud. Están jugando con nosotros” – El País 2020, published 10 October. Full-text: https://elpais.com/sociedad/2020-10-09/estan-primando-mas-la-politica-que-la-salud-estan-jugando-con-nosotros.html

El embrollo político y jurídico de las últimas semanas en Madrid pone en cuestión la credibilidad de las medidas entre la población. Los expertos advierten de que el retraso en las restricciones ha provocado más enfermos.