Copy-editor: Rob Camp
Vaccines
Paper of the Day
Voysey M, Costa Clemens SA, Madhi SA. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet February 19, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00432-3/fulltext
In the case of the ChAdOx1 nCoV-19 (AZD1222) vaccine, it may be better to wait with the second shot. This pre-specified pooled analysis of AstraZeneca’s vaccine trials suggests that a 3-month dose interval might have advantages over a program with a shorter dosing interval. In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81% at ≥ 12 weeks) than in those with a short interval (vaccine efficacy 55% at < 6 weeks).
Epidemiology
Tian L, Li X, Qi F et al. Harnessing peak transmission around symptom onset for non-pharmaceutical intervention and containment of the COVID-19 pandemic. Nat Commun February 19, 2021. https://www.nature.com/articles/s41467-021-21385-z
Epidemiological modeling study, focusing on transmission around symptom onset by both pre-symptomatic and symptomatic viral carriers.
Immunology
Sette A, Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021 Feb 18;184(4):861-880. PubMed: https://pubmed.gov/33497610 . Full-text: https://doi.org/10.1016/j.cell.2021.01.007
CD4+ T cells, CD8+ T cells, and neutralizing antibodies all contribute to control of SARS-CoV-2 in both non-hospitalized and hospitalized cases of COVID-19. In this brilliant review of the adaptive immune response to SARS-CoV-2, Alessandro Sette and Shane Crotty discuss the specific functions and kinetics of these adaptive immune responses, as well as their interplay with innate immunity and implications for COVID-19 vaccines and immune memory against re-infection.
Lee HK, Knabl L, Pipperger L, et al. Immune transcriptomes of highly exposed SARS-CoV-2 asymptomatic seropositive versus seronegative individuals from the Ischgl community. Sci Rep 11, 4243 (2021). https://www.nature.com/articles/s41598-021-83110-6
The ski resort of Ischgl, Austria experienced a superspreading event in early March 2020. In April, a seroprevalence of approximately 42% was found in the Ischgl population (n = 1867), with approximately 17% of these being asymptomatic. This comparative investigation of immune cell transcriptomes from 43 asymptomatic seropositive and 52 highly exposed seronegative individuals 4 – 6 weeks following the superspreading event showed no statistically significant differences. These results demonstrate that development of an antibody response to COVID-19 following viral exposure and seroconversion in asymptomatic cases is not necessarily associated with sustained alterations in the immune system transcriptome.
Rha MS, Jeong HW, Ko JH, et al. PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19. Immunity. 2021 Jan 12;54(1):44-52.e3. PubMed: https://pubmed.gov/33338412. Full-text: https://doi.org/10.1016/j.immuni.2020.12.002
More about SARS-CoV-2-specific CD8+ T cells. The highlights: 1) SARS-CoV-2-specific CD8+ T cells are effector memory cells in convalescent individuals; 2) CCR7+CD45RA+ cells are increased among SARS-CoV-2-specific cells in the late phase; 3) SARS-CoV-2-specific CD8+ T cells have fewer IFN-γ+ cells than flu-specific cells; 4) PD-1-expressing SARS-CoV-2-specific CD8+ T cells are not exhausted but functional.
Wheatley AK, Juno JA, Wang JJ, et al. Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19. Nat Commun 12, 1162 (2021). https://www.nature.com/articles/s41467-021-21444-5
This longitudinal cohort of 64 participants who recovered from COVID-19 suggests that SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long term protection. Both neutralizing and binding antibody responses decay after recovery from COVID-19, assessed by both polyclonal assays and at the level of single antibody clonotypes with a mass spectrometry-based assay.
Supasa P, Daming Z, Dejnirattisai W, et al. Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera. Cell 2021, published 18 February. Full-text: https://www.cell.com/cell/fulltext/S0092-8674(21)00222-1
Gavin Screaton, Piyada Supasa and colleagues mapped the impact of the N501Y mutation by structure/function analysis of a large panel of well-characterised monoclonal antibodies. B.1.1.7 was harder to neutralize but widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed (Supasa 2021).
Clinical
Jeffery-Smith A, Iyanger N, Williams SV, et al. Antibodies to SARS-CoV-2 protect against re-infection during outbreaks in care homes, September and October 2020. Euro Surveill. 2021 Feb;26(5):2100092. PubMed: https://pubmed.gov/33541486. Full-text: https://doi.org/10.2807/1560-7917.ES.2021.26.5.2100092
Prior infection with SARS-CoV-2 as determined by antibody or RT-PCR positivity was highly protective at 4 months. Only one re-infection occurred in a seropositive staff member, whose antibodies were boosted following re-infection.
Rha MS, Jeong HW, Ko JH, et al. PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19. Immunity. 2021 Jan 12;54(1):44-52.e3. PubMed: https://pubmed.gov/33338412. Full-text: https://doi.org/10.1016/j.immuni.2020.12.002
More about SARS-CoV-2-specific CD8+ T cells. The highlights: 1) SARS-CoV-2-specific CD8+ T cells are effector memory cells in convalescent individuals; 2) CCR7+CD45RA+ cells are increased among SARS-CoV-2-specific cells in the late phase; 3) SARS-CoV-2-specific CD8+ T cells have fewer IFN-γ+ cells than flu-specific cells; 4) PD-1-expressing SARS-CoV-2-specific CD8+ T cells are not exhausted but functional.
Treatment
Qiao J, Li YS, Zeng R. SARS-CoV-2 Mpro inhibitors with antiviral activity in a transgenic mouse model. Science 18 Feb 2021: eabf1611. https://science.sciencemag.org/content/early/2021/02/17/science.abf1611.full
The authors designed and synthesized 32 new bicycloproline-containing protease inhibitors derived from either boceprevir or telaprevir, two (older) approved drugs for hepatitis C. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays and displayed good pharmacokinetic properties and safety in rats.
Raman AS, Barge VB, Darivenula AK, et al. A Phase II Safety and Efficacy Study on Prognosis of Moderate Pneumonia in COVID-19 patients with Regular Intravenous Immunoglobulin Therapy. J Infect Dis. 2021 Feb 15:jiab098. PubMed: https://pubmed.gov/33585890 . Full-text: https://doi.org/10.1093/infdis/jiab098
Immunoglobulins for COVID-19? In this open-label, multicenter, randomized study on COVID-19 patients with moderate pneumonia in India, 100 patients were randomized 1:1 either to receive IVIG + standard of care (SOC) or SOC only. Duration of hospital stay was significantly shorter in the IVIG group compared to that of SOC alone (7,7 vs. 17,5 days). Duration for normalization of body temperature, oxygen saturation and mechanical ventilation were significantly shorter in IVIG compared to SOC. Percentages of patients on mechanical ventilation were not significantly different (24% vs 38%). Median time to RT-PCR negativity was significantly shorter with IVIG than SOC (7 vs 18 days).
Beyond Corona
Killock D. Unleashing the immune system against cancer. Nature 2020, published 10 December. Full-text: https://www.nature.com/articles/d42859-020-00076-7
2010 witnessed a second landmark in the development of immune-checkpoint inhibitors (ICIs) when ipilimumab became the first agent shown to prolong overall survival (OS) in patients with advanced-stage melanoma.
French
If you read French, read Stromboni C. Sous la pression du variant anglais, Dunkerque voit flamber l’épidémie de Covid-19. Le Monde 2021, published 20 February. Full-text : https://www.lemonde.fr/planete/article/2021/02/20/sous-la-pression-du-variant-anglais-dunkerque-voit-flamber-l-epidemie-de-covid-19_6070631_3244.html
Le taux d’incidence est trois fois plus élevé que la moyenne nationale, et la part du variant « B.1.1.7 » estimée à 72 % des cas. L’hôpital voit affluer de nombreux patients, souvent plus jeunes.
Dagorn G. Covid-19 : comment le variant B.1.1.7, apparu en Angleterre, menace de relancer l’épidémie en France. Le Monde 2021, published 19 February. Full-text : https://www.lemonde.fr/les-decodeurs/article/2021/02/19/comment-le-variant-britannique-menace-de-destabiliser-l-epidemie-en-france_6070563_4355770.html
En deux mois, ce variant a précipité l’Angleterre dans une nouvelle phase de l’épidémie, et pourrait provoquer une troisième vague tout aussi brutale en France.