Copy-editor: Rob Camp
Virology
* * * Paper of the Day * * *
Starr TN, Greaney AJ, Addetia A. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Science 25 Jan 2021:eabf9302. Full-text: https://doi.org/10.1126/science.abf9302
Incredible work, mapping how all mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies from Regeneron and Lilly. There was not only a single amino acid mutation that fully escapes the REGN-COV2 cocktail but also mutations that were selected in a persistently infected patient treated with REGN-COV2, as well those already present in circulating SARS-CoV-2 strains. According to Tyler Starr and colleagues, it is “concerning that so many escape mutations impose little cost on RBD folding or receptor affinity, and that some are already present at low levels among circulating viruses”.
Johnson BA, Xie X, Bailey AL et al. Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis. Nature January 25, 2021. Full-text: https://doi.org/10.1038/s41586-021-03237-4
SARS-CoV-2 has a furin cleavage site (PRRAR) in its spike protein that is absent in other CoVs. It has been postulated to be key to disease causing capability. To explore this, Bryan Johnson and colleagues from Texas generated a mutant SARS-CoV-2 deleting the furin cleavage site (ΔPRRA). SARS-CoV-2 ΔPRRA replicates had faster kinetics, improved fitness in Vero E6 cells, and reduced spike protein processing as compared to parental SARS-CoV-2. However, the ΔPRRA mutant had reduced replication in a human respiratory cell line and was attenuated in both hamster and K18-hACE2 transgenic mouse models of SARS-CoV-2 pathogenesis. Importantly, COVID-19 patient sera and RBD mAbs had lower neutralization values against the ΔPRRA mutant versus parental SARS-CoV-2.
Claro IM, da Silva Sales FC, Ramundo MS, Candido DS, Silva CAM, de Jesus JG, et al. Local transmission of SARS-CoV-2 lineage B.1.1.7, Brazil, December 2020. Emerg Infect Dis. January 25, 2021. Full-text: https://doi.org/10.3201/eid2703.210038
In December 2020, research surveillance detected the new SARS-CoV-2 variant B.1.1.7 in São Paulo, Brazil. Rapid genomic sequencing and phylogenetic analysis revealed two distinct introductions of the lineage. One patient reported no international travel. According to the authors, “there may be more infections with this lineage in Brazil than reported”. It would be surprising if not.
Diagnosis
Bal A, Destras G, Gaymard A. Two-step strategy for the identification of SARS-CoV-2 variant of concern 202012/01 and other variants with spike deletion H69–V70, France, August to December 2020. Eurosurveillance Volume 26, Issue 3, 21/Jan/2021. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.3.2100008
A technical paper, reporting a two-step strategy that enables the timely detection of VOC 202012/01, as well as other variants carrying ΔH69/ΔV70. This strategy allowed the first detection of the VOC 202012/01 in France.
Clinical
Kooistra EJ, de Nooijer AH, Claassen WJ et al. A higher BMI is not associated with a different immune response and disease course in critically ill COVID-19 patients. Int J Obes (2021). https://doi.org/10.1038/s41366-021-00747-z
In 67 COVID-19 patients from Nijmegen, Netherlands requiring mechanical ventilation in the ICU, a higher BMI was not related to a different immunological response, unfavorable respiratory mechanics, or impaired outcome. The concentrations and kinetics of clinical inflammatory parameters and respiratory mechanics were similar in both groups.
Lowe KE, Zein J, Hatipoğlu U, et al. Association of Smoking and Cumulative Pack-Year Exposure With COVID-19 Outcomes in the Cleveland Clinic COVID-19 Registry. JAMA Intern Med. Published online January 25, 2021. Full-text: https://doi.org/10.1001/jamainternmed.2020.8360
Time to quit! Among 7102 patients from Cleveland, 6020 (84,8%) were never smokers, 172 (2,4%) were current smokers, and 910 (12,8%) were former smokers. There was a dose-response association between pack-years and adverse COVID-19 outcomes. Patients who smoked more than 30 pack-years had a 2,25 times higher odds of hospitalization (95% CI: 1,76-2,88) and were 1,89 times more likely to die following a COVID-19 diagnosis (95% CI: 1,29-1,76) when compared with never smokers.
Collateral
Leitner MC, Richlan F. Analysis System for Emotional Behavior in Football (ASEB-F): matches of FC Red Bull Salzburg without supporters during the COVID-19 pandemic. Humanit Soc Sci Commun 8, 14 (2021). Full-text: https://doi.org/10.1057/s41599-020-00699-1
Less aggression! This study (our “alternative” paper of the day) has evaluated the effect of missing crowds in football on the emotions and behavior of players, staff and officials. These data from Austria show that in “ghost games” overall, “emotional situations” declined by 20%. More data on this topic (other leagues, other sports) are eagerly awaited!
Chen CY, Chen IH, O’Brien KS et al. Psychological distress and internet-related behaviors between schoolchildren with and without overweight during the COVID-19 outbreak. Int J Obes (2021). Full-text: https://doi.org/10.1038/s41366-021-00741-5
Online survey among 1357 schoolchildren (mean age = 10,7 years), showing that overweight kids had significantly higher levels of COVID-19 infection fear, stress, depression, perceived weight stigma, and problematic social media use than those not overweight.
Partridge E, McCleery E, Cheema R, et al. Evaluation of Seasonal Respiratory Virus Activity Before and After the Statewide COVID-19 Shelter-in-Place Order in Northern California. JAMA Netw Open January 2021; 4(1):e2035281. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.35281
Using interrupted time series analysis of testing for viral respiratory pathogens, this study found that statistically significant lower rates of common community respiratory viruses appeared to be associated with a shelter-in-place order during the coronavirus pandemic. Decreases were most pronounced for influenza (93%) and for rhinovirus or enterovirus (81%). Lower rates of post-exposure viral activity were seen for respiratory syncytial virus, parainfluenzavirus, coronaviruses, and adenoviruses, however, these associations were not statistically significant.
Treatment
White KM, Rosales, Yildiz S. Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A. Science 25 Jan 2021:eabf4058. Full-text: https://doi.org/10.1126/science.abf4058
SARS-CoV-2 viral proteins interact with the eukaryotic translation machinery and inhibitors of translation have potent antiviral effects. Plitidepsin has been clinically developed for the treatment of multiple myeloma with a well-established safety profile and pharmacokinetics. Kris White and colleagues report that the drug possesses antiviral activity 27,5-fold more potent than remdesivir against SARS-CoV-2 in vitro, with limited toxicity in cell culture. There was in vivo efficacy in two mouse models of SARS-CoV-2 infection with a reduction of viral replication in the lungs by two orders of magnitude using prophylactic treatment.
French
If you read French, read Covid-19 : le variant anglais représente près d’un cas positif sur dix en Ile-de-France. Le Monde, published 26 January. Full-text : https://www.lemonde.fr/planete/article/2021/01/26/covid-19-une-pme-sur-deux-craint-de-ne-pas-pouvoir-supporter-un-troisieme-confinement_6067608_3244.html
Selon l’AP-HP, ce variant du SARS-CoV-2 représente 9,4 % de 1 080 cas dépistés en Ile-de-France entre les 11 et 21 janvier. Il y a trois semaines, une « enquête flash » avait constaté un taux de 2,5 % au niveau national.
Ducourtieux C. Le Covid-19 a fait plus de 100 000 morts au Royaume-Uni : pourquoi un tel bilan ? Le Monde, published 26 January. Full-text : https://www.lemonde.fr/international/article/2021/01/26/le-covid-19-a-fait-plus-de-100-000-morts-au-royaume-uni-pourquoi-un-tel-bilan_6067682_3210.html
Le pays est le plus endeuillé d’Europe et, proportionnellement à sa population, l’un des plus affectés dans le monde, devant les Etats-Unis ou le Mexique.