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By Christian Hoffmann &
Bernd S. Kamps
Aschwanden C. The false promise of herd immunity for COVID-19. Nature News Feature October 21. Full-text: https://doi.org/10.1038/d41586-020-02948-4
Herd immunity has recently been discussed as a desirable result of wide-scale vaccination programs. (High levels of vaccination-induced immunity in the population benefits those who can’t receive or sufficiently respond to a vaccine, such as people with compromised immune systems.) However, discussing herd immunity as a tool in the absence of vaccines has never been heard of before the SARS-CoV-2 pandemic. If you are tired and frustrated with distancing, lockdown and curfews and tempted by the notion of herd immunity (better: ‘herd protection’), read this brilliant article by Nature’s leading science writer Christie Aschwanden. Find out why proposals to largely let the virus run its course — embraced by Donald Trump’s administration and others — could bring untold death and suffering. Seasonal coronaviruses that cause common colds provoke a waning immunity that seems to last approximately a year. Until proof of the contrary, we should assume immunity to SARS-CoV-2 to be comparable. Without vaccines there will be no herd immunity for the foreseeable future.
Adlhoch C, Pebody R. What to expect for the influenza season 2020/21 with the ongoing COVID-19 pandemic in the World Health Organization European Region. Euro Surveill. 2020;25(42):pii=2001816. Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.42.2001816
Less flu cases in this season? The positivity rate of 0.2% in the 2020 inter-seasonal period was lower than the average (1.1%) observed over the previous five inter-seasonal periods. However, although COVID-19 prevention and control measures will also support influenza prevention, influenza remains a threat to human health and a potential burden on the healthcare system.
Youk J, Kim T, Evans KV. Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2. Cell Rep October 21, 2020. Full-text: https://doi.org/10.1016/j.stem.2020.10.004
The cellular response of human alveolar type 2 (hAT2) cells to SARS-CoV-2 remains elusive, due to difficulty in the long-term expansion of pure hAT2 cells. Jeonghwan Youk and colleagues now developed a technique for long-term, feeder-free human 3D alveolar type 2 cell cultures (h3ACs). According to the authors, SARS-CoV-2 infected h3ACs showed remarkable cellular and transcriptional changes far more clearly than other models, including h3BCs and 2D Vero cell lines, showing cellular tropism in the viral replication and transcription as well as the resultant reaction from the host cell.
Katsura H, Sontake V, Tata A, et al. Human lung stem cell-based alveolospheres provide insights into SARS-CoV-2 mediated interferon responses and pneumocyte dysfunction. Cell Rep October 21, 2020. Full-text: https://doi.org/10.1016/j.stem.2020.10.005
Hiroaki Katsura from Duke University, Durham, USA and colleagues present another new feeder-free, scalable, chemically-defined, and modular alveolosphere culture system for propagation and differentiation of human alveolar type 2 cells (AT2s/pneumocytes) derived from primary lung tissue. Cultured pneumocytes expressed the SARS-CoV-2 receptor ACE2 and could be infected with virus. Cells retained the cardinal features of AT2s, including the ability to self-renew, produce surfactants, and differentiate into AT1s. This model may offer a unique system for studying SARS-CoV-2 infection and developing effective therapies for COVID-19 and other respiratory diseases.
Ferretti AP, Kula T, Wang Y, et al. Unbiased screens show CD8+ T cells of COVID-19 patients recognize shared epitopes in SARS-CoV-2, most of which are not located in the Spike protein. Immunity, October 20, 2020. Full-text: https://doi.org/10.1016/j.immuni.2020.10.006
Which peptide sequences in SARS-CoV-2 are recognized by the memory CD8+ T cells of COVID-19 patients? Andrew P. Ferretti and colleagues found that CD8+ T cells predominantly recognized 3-8 shared epitopes for each HLA type studied. Of note, around ∼90% of shared epitopes were not located in the Spike protein, but in ORF1ab or the nucleocapsid protein. CD8+ T cells generally did not cross-react with epitopes in the four seasonal coronaviruses.
Bell BP, Romero JR, Lee GM. Scientific and Ethical Principles Underlying Recommendations from the Advisory Committee on Immunization Practices for COVID-19 Vaccination Implementation. JAMA. 2020 Oct 22. PubMed: https://pubmed.gov/33090194. Full-text: https://doi.org/10.1001/jama.2020.20847
Discover how the US wants to distribute a vaccine. This viewpoint discusses possible prioritization scenarios. “Phase Ia” includes health care personnel who have the potential for direct or indirect exposure to patients or infectious materials. This group comprises an estimated 20 million (!) people. We will later come back to Phase Ib (and the rest) maybe in 2022.
Kreps S, Prasad S, Brownstein JS. Factors Associated With US Adults’ Likelihood of Accepting COVID-19 Vaccination. JAMA Netw Open. 2020;3(10):e2025594. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.25594
But who will accept such a vaccine (see previous paper). And when? Sarah Kreps and colleagues asked 1971 US adults, analyzing factors associated with willingness and individual preferences. Some interesting findings: The marginal mean willingness to receive a vaccine was lowest when the vaccine was recommended by President Trump. Willingness was slightly (but not significantly) higher with former Vice President Biden and significantly higher given a CDC or WHO endorsement. Respondents who indicated Democratic political partisanship were significantly more likely to report willingness than those who indicated Republican political partisanship. A vaccine originating in China was associated with a 10% lower willingness.
Rubin R. The Challenges of Expanding Rapid Tests to Curb COVID-19. JAMA October 21, 2020. Full-text: https://doi.org/10.1001/jama.2020.21106
BinaxNOW is one of 6 point-of-care rapid antigen tests that had received an Emergency Use Authorization from the FDA as of October 10. The Trump administration awarded a contract for $760 million to Abbott for delivery of 150 million tests (Abbott said it would ship 50 million tests per month beginning in October). However, rapid point-of-care tests alone can’t halt the spread of SARS-CoV-2: this interesting article describes how the rapid test BinaxNOW fueled the White House COVID-19 cluster.
Salvarani C, Dolci G, Massari M, et al. Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia. A Randomized Clinical Trial. JAMA Intern Med October 20, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.6615
The second RCT showing that tocilizumab (TCZ) doesn’t work in patients with less severe disease. This prospective, open-label RCT randomized patients hospitalized with COVID-19 pneumonia to receive TCZ or standard of care in 24 hospitals in Italy. Among 126 patients with a partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio between 200 and 300 mm Hg at enrolment, the rate of the primary clinical end point (clinical worsening) was not significantly different between the control group and the TCZ group. The proportion of patients discharged within 14 and 30 days was the same (rate ratio, 0.99; 95% CI, 0.73-1.35; and 0.98; 95% CI, 0.87-1.09; respectively). According to the authors, however, their results “do not allow ruling out the possible role of tocilizumab in reducing the risk of death or intubation in patients presenting with more advanced disease”. Let’s hope.
Gupta S, Wang W, Hayek SS, et al. Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. JAMA Intern Med October 20, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.6252
Does it work in severe COVID-19? This multicenter cohort study that included 3924 critically ill patients admitted to participating intensive care units (ICU) at 68 hospitals across the US, patients were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. The risk of in-hospital death was estimated to be lower with TCZ. A total of 1544 patients (39,3%) died, including 125/433 (28,9%) treated with TCZ and 1419/3491 (40,6%) not treated with the drug. However, this was an uncontrolled study and TCZ patients were younger, had fewer co-morbidities and were more likely to receive corticosteroids on ICU admission. According to the authors, the findings “may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed”. Again, let’s hope.