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Han Y, Duan X, Yang L, et al. Identification of SARS-CoV-2 Inhibitors using Lung and Colonic Organoids. Nature 2020, October 28. Full-text: https://doi.org/10.1038/s41586-020-2901-9
The authors developed a lung organoid model using human pluripotent stem cells (hPSC-LOs). The hPSC-LOs, particularly alveolar type II-like cells, were permissive to SARS-CoV-2 infection, and showed robust induction of chemokines upon SARS-CoV-2 infection, similar to what is seen in COVID-19 patients. The authors also generated complementary hPSC-derived colonic organoids (hPSC-COs) to explore the response of colonic cells to SARS-CoV-2 infection. Both cell models can serve as disease models to study SARS-CoV-2 infection and provide a valuable resource for drug screening to identify candidate COVID-19 therapeutics.
Kirby T. COVID-19 human challenge studies in the UK. Lancet October 30, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30518-X
Some thoughts about feasibility and ethics of human challenge trials that could potentially accelerate the development of vaccines. The first study phase, which could begin in January 2021, aims to discover the smallest amount of virus it takes to cause the infection in up to 90 healthy young people, aged between 18 and 30 years. The study will probably take place in the high-level isolation unit of the Royal Free Hospital, London, UK. Some commentators have questioned both the timing and the ethical dilemmas presented by the study.
Hutchins HJ, Wolff B, Leeb R, et al. COVID-19 Mitigation Behaviors by Age Group — United States, April–June 2020. MMWR Morb Mortal Wkly Rep 2020;69:1584–1590. Full-text: http://dx.doi.org/10.15585/mmwr.mm6943e4
This report of 6,475 online or telephone surveys provides four important insights into the practice of mitigation behaviors among U.S. adults to prevent the spread of SARS-CoV-2. First, the majority of U.S. adults reported engaging in most or all of the six mitigation behaviors assessed. Second, age was an important determinant of engagement in mitigation behaviors overall. A smaller percentage of adults aged <60 years, particularly those aged 18–29 years, reported engaging in the mitigation behaviors assessed compared with adults aged ≥60 years. Third, while reported use of face masks increased significantly across all age groups over time, other reported mitigation behaviors declined or did not change significantly across age groups. Finally, compared with adults who reported wearing a mask, those who did not report mask use also reported engaging in significantly fewer other mitigation behaviors during the same period, with significant declines in all other behaviors from April to June.
Grijalva CG, Rolfes MA, Zhu Y, et al. Transmission of SARS-COV-2 Infections in Households — Tennessee and Wisconsin, April–September 2020. MMWR Morb Mortal Wkly Rep. ePub: 30 October 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6944e1
Important study (because prospective). After enrollment, 101 index patients and 191 household members were trained remotely by study staff members to complete symptom diaries and obtain self-collected specimens, nasal swabs only or nasal swabs and saliva samples, daily for 14 days. In this preliminary analysis of the first 7 days, transmission of SARS-CoV-2 among household members was common, and secondary infection rates were higher (35%) than have been previously reported. Secondary infections occurred rapidly and were high across all racial/ethnic groups or rage groups. The authors conclude that persons who suspect that they might have COVID-19 should isolate, stay at home, and use a separate bedroom and bathroom if feasible. Isolation should begin before seeking testing and before test results become available. All household members, including the index patient, should start wearing a mask in the home, particularly in shared spaces where appropriate distancing is not possible. Close household contacts of the index patient should also self-quarantine, to the extent possible, particularly staying away from those at higher risk of getting severe COVID-19.
Shah ASV, Wood R, Gribben C. Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study. BMJ October 28, 2020;371:m3582. Full-text: http://dx.doi.org/10.1136/bmj.m3582
This large cohort from Scotland comprising 158,445 healthcare workers (HCW) and 229,905 household members revealed that HCW and their households contributed a sixth of all COVID-19 cases admitted to hospital. Patient facing HCW and their household members had threefold and twofold increased risks of admission with COVID-19. However, the absolute risk of admission was low overall, being 0.20% (181/90733), 0.07% (23/32615), and 0.11% (39/35097) in patient facing, non-patient facing, and undetermined HCW.
Goldstein E, Lipsitch M, Cevik M, et al. On the effect of age on the transmission of SARS-CoV-2 in households, schools and the community. J Inf Dis 29 October 2020, jiaa691. Full-text: https://doi.org/10.1093/infdis/jiaa691
Literature review of all papers published before October 5, 2020. Compared to younger/middle aged adults, susceptibility to infection for children aged less than 10 years of age seems to be significantly lower, while estimated susceptibility to infection in adults aged over 60 years is higher. There is some evidence that given limited control measures, SARS-CoV-2 may spread robustly in secondary/high schools, and to a lesser degree in primary schools, with class size possibly affecting that spread. There is also evidence of more limited spread in schools when some mitigation measures are implemented. Several potential biases that may affect these studies are discussed.
Fontana IC, Bongarzone S, Gee A. PET Imaging as a Tool for Assessing COVID-19 Brain Changes. Trends Neurosc October 29, 2020. Full-text: https://doi.org/10.1016/j.tins.2020.10.010
A brief overview of positron emission tomography (PET) applications that could advance current understanding of CNS pathophysiological alterations associated with SARS-CoV-2 infection. Apart from testing for brain changes during the acute phase of the disease, longitudinal assessment of COVID-19 patients using PET may be conducted to examine whether brain changes are transient or long-lasting.
Mastrangelo A, Germinarkio BN, Ferrante M, et al. Candidemia in COVID-19 patients: incidence and characteristics in a prospective cohort compared to historical non-COVID-19 controls. Clinical Infectious Diseases, 30 October 2020, ciaa1594. Full-text: https://doi.org/10.1093/cid/ciaa1594
This study found an increased incidence of candidemia in hospitalized patients with COVID-19 compared to a historical non-COVID-19 cohort (11 vs. 1.5 cases per 10.000-PDFU). The authors found no imbalance in several predisposing risk factors for candidemia, with the notable exception of a higher proportion of subjects in ICU and on immunosuppressive agents in the COVID-19 cohort.
Yu J, Yuan X, Chen H, Chaturvedi S, Braunstein EM, Brodsky RA. Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition. Blood. 2020 Oct 29;136(18):2080-2089. PubMed: https://pubmed.gov/32877502. Full-text: https://doi.org/10.1182/blood.2020008248
COVID-19 often results in hypercoagulability, thrombotic microangiopathy, and severe endothelial damage. The role of complement activation and its contribution to disease severity is increasingly recognized, but the mechanism of complement activation was unknown. Here, Robert A Brodsky and collegues from John Hopkins University demonstrate that SARS-CoV-2 spike protein, but not spike protein from benign human coronaviruses, are potent activators of the alternative pathway of complement (APC). Both S1 and S2 subunits activate the APC, but only in the presence of cells, demonstrating that APC activation is occurring on the cell surface and not the fluid phase. Both C5 inhibitors and ACH145951, a small molecule factor D inhibitor, were able to block the APC activation, preventing complement-mediated damage.
Mattay MA, Thompson BT. Dexamethasone in hospitalised patients with COVID-19: addressing uncertainties. Lancet Resp Med October 29, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30503-8
An important comment on unanswered questions regarding the use of dexamethasone. Michael Matthay and Taylor Thompson discuss the limitations of the pragmatic RECOVERY trial (huge number of excluded patients, no data on oxygen support, no use of remdesivir, no data on viral clearance etc). They also discuss the steps need to be taken to learn more about the effects of dexamethasone in hospitalised patients with COVID-19.
If you read Spanish, read Mouzo J, Valdés I, Battista G (vídeo). Los médicos en las UCI: “Aún no es el infierno, pero sí el purgatorio”. El País 2020, published 31 October. Full-text: https://elpais.com/sociedad/2020-10-30/los-medicos-en-las-uci-aun-no-es-el-infierno-pero-si-el-purgatorio.html
Una cuarta parte de las UCI españolas están ocupadas por pacientes con covid-19. EL PAÍS entra en dos unidades, en Madrid y Barcelona, que bordean el colapso
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