Copy-editor: Rob Camp
Epidemiology
Yoon Y, Choi G-J, Kim JY, Kim K-R, Park H, Chun JK, et al. Childcare exposure to severe acute respiratory syndrome coronavirus 2 for 4-year-old presymptomatic child, South Korea. Emerg Infect Dis 2020 November 30, 2020. Full-text: https://doi.org/10.3201/eid2702.203189
An epidemiologic investigation of potential exposure of a presymptomatic child who attended a childcare center in South Korea: a 4-year-old child, probably infected by his grandmother, attended the center during the presymptomatic period (February 19–21, 2020). Fever developed on February 22, and he was given a diagnosis of SARS-CoV-2 infection on February 27. At the center, 190 persons were identified as contacts; 44 (23.2%) were defined as close contacts (37 children and 7 adults). All 190 persons were negative for SARS-CoV-2 on days 8–9 after the last exposure. This investigation adds indirect evidence of potentially low infectivity in a childcare setting with exposure to a presymptomatic child.
Virology
Popa A, Genger JW, Nicholson MD. Genomic epidemiology of superspreading events in Austria reveals mutational dynamics and transmission properties of SARS-CoV-2. Science Translational Medicine 23 November 2020: eabe2555. Full-text: https://doi.org/10.1126/scitranslmed.abe2555
Alexandra Popa, Andreas Bergthaler and colleagues from Vienna identified major SARS-CoV-2 clusters during the first wave of infections in Austria and performed deep whole-genome sequencing of 572 virus samples. Their genomic epidemiology analysis enabled the retrospective identification of SARS-CoV-2 chains of transmission and international hotspots. Taking advantage of a well-described and independently confirmed transmission network with 39 transmission events, the authors also found that the number of viral particles transmitted from one individual to another that contributed productively to the infection was on average higher than 1000. This suggests that social distancing and mask wearing may be effective even when they cannot prevent the spread of all viral particles.
Immunology
Bacher P, Rosati E, Esser D, et al. Low avidity CD4+ T cell responses to SARS-CoV-2 in unexposed individuals and humans with severe COVID-19. Immunity November 26, 2020. Full-text: https://doi.org/10.1016/j.immuni.2020.11.016
Interesting work, arguing against a protective role for CCCoV (common cold coronavirus) reactive T cells in SARS-CoV-2 infection. Petra Bacher from UKSH (Kiel, Germany) and colleagues employed antigen-specific T cell enrichment to characterize SARS-CoV-2-specific T cells from 55 healthy donors and 56 COVID-19 patients including their avidity and clonality as well as their cross-reactivity to CCCoV and other viruses. First, pre-existing T cell memory was common in humans, correlated with the size of the CD4+ memory repertoire rather than with CCCoV-specific memory, and displayed only low functional avidity. Second, robust CD4+ T cell responses against CCCoV were prevalent in the population; however, T cells reacting to CCCoV were not present among SARS-CoV-2-specific T cells in COVID-19 patients. Third, in severe COVID-19 patients, SARS-CoV-2-specific CD4+ T cells also displayed low functional avidity and TCR clonality, although their frequencies increased with disease severity.
Salahudeen AA, Choi SS, Rustagi A et al. Progenitor identification and SARS-CoV-2 infection in human distal lung organoids. Nature November 24, 2020. Full-text: https://doi.org/10.1038/s41586-020-3014-1
The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange. This work by Ameen A. Salahudeen, Shannon S. Choi and colleagues from Chicago helps to study these cells. The authors have established a long-term feeder-free, chemically defined culture of distal lung progenitors as organoids derived from single adult human alveolar epithelial type II (AT2) cells. Their culture experiments identified unsuspected basal cell functional heterogeneity and established a facile in vitro organoid model for human distal lung infections including COVID-19-associated pneumonia.
Vaccine
Sanchez-Felipe L, Vercruysse T, Sharma S et al. A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate. Nature December 1, 2020. Full-text: https://doi.org/10.1038/s41586-020-3035-9
Yellow Fever 17D (YF17D) is a small RNA live-attenuated virus with limited vector capacity. The YF17D vaccine is known to rapidly induce broad multi-functional innate, humoral and cell-mediated immune responses that may result in life-long protection following a single vaccine dose in nearly all vaccinees. These favorable characteristics translate also to vectored vaccines based on the YF17D backbone. Consequently, YF17D is used as vector in two licensed human vaccines, generated by swapping genes encoding the YF17D surface antigens for those of Japanese encephalitis or dengue viruses. Here, the authors describe the discovery of a live virus-vectored SARS-CoV-2 vaccine candidate using the YF17D vaccine as vector to express a non-cleavable prefusion form of the SARS-CoV-2 Spike antigen. Safety, immunogenicity and efficacy after a single dose are shown in several animal models such as hamsters, mice and macaques.
Transmission
Bulfone TC, Malekinejad M, Rutherford, et al. Outdoor Transmission of SARS-CoV-2 and Other Respiratory Viruses, a Systematic Review. J Inf Dis November 29, 2020. Full-text: https://doi.org/10.1093/infdis/jiaa742
According to this review, existing evidence supports the widely held belief that the risk of SARS-CoV-2 transmission is lower outdoors. Moreover, historical evidence gleaned from influenza outbreaks further support the lower risk of transmission outdoors. However, there are significant gaps in our understanding of specific pathways. It is important to note that infections are possible outdoors and the advantage may be overtaken by relaxed mitigation efforts (think of the White House outbreak on September 26).
Clinical
Mackey K, Ayers CK, Kondo KK. Racial and Ethnic Disparities in COVID-19–Related Infections, Hospitalizations, and Deaths. Annals Int Medicine 1 December 2020. Full-text: https://doi.org/10.7326/M20-6306
Differences in health care access and exposure risk may be driving higher infection and mortality rates. This systematic review revealed that African-American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection, hospitalization, and COVID-19-related mortality compared with non-Hispanic White populations, but not higher case-fatality rates (moderate- to high-strength evidence). Asian populations experience similar outcomes to non-Hispanic White populations (low-strength evidence). Outcomes for other racial/ethnic groups have been insufficiently studied. Health care access and exposure factors may underlie the observed disparities more than susceptibility due to co-morbid conditions (low-strength evidence).
Treatment
Young B, Tan TT, Leo YS. The place for remdesivir in COVID-19 treatment. Lancet Inf Dis November 26, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30911-7
Is there is a place for remdesivir? Last week, the WHO said no (https://www.who.int/news-room/feature-stories/detail/who-recommends-against-the-use-of-remdesivir-in-covid-19-patients). In their comment on current data, Barnaby Young and colleagues from Singapore are not that strict. They believe that the natural history of COVID-19 suggests a window of opportunity for antivirals before fulminant inflammation sets in. However, they conclude that “for now, remdesivir is an important COVID-19 treatment option only in selected patient groups”.
Dangerfield TL, Huang NZ, Johnson KA. Remdesivir is effective in combating COVID-19 because it is a better substrate than ATP for the viral RNA-dependent RNA polymerase. iScience November 27, 2020. Full-text: https://doi.org/10.1016/j.isci.2020.101849
Tyler L. Dangerfield and colleagues compared binding and incorporation parameters for nucleoside analogs such as remdesivir relative to their natural counterparts (ATP). The specificity constant for remdesivir triphosphate incorporation was higher than that for competing ATP. Would be nice to see this effect in vivo.
Sörgel F, Nalin JJ, Hagman H, et al. Pharmacokinetics of remdesivir in a COVID-19 patient with end-stage renal disease on intermittent haemodialysis. Journal of Antimicrobial Chemotherapy November 30,2020. Full-text: https://doi.org/10.1093/jac/dkaa500
Jan Rybniker from Cologne and colleagues report the pharmacokinetics of remdesivir and its metabolites and the treatment outcome in a patient on renal replacement therapy without residual renal function suffering from severe COVID-19.
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By Christian Hoffmann &
Bernd Sebastian Kamps
Copy-editor: Rob Camp