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Truelove S, Abrahim O, Altare C, et al. The potential impact of COVID-19 in refugee camps in Bangladesh and beyond: A modeling study. PLoS Med 2020 Jun 16;17(6):e1003144. PubMed: https://pubmed.gov/32544156 . Full-text: https://doi.org/10.1371/journal.pmed.1003144
Bangladesh hosts almost 1 million Rohingya refugees from Myanmar, with 600,000 concentrated in the Kutupalong-Balukhali Expansion Site. Using different transmission models and considering the age distribution in the camp, the authors expect 2,040-2,880 deaths (assuming that age was the primary determinant of infection severity and hospitalization). They also expect that comorbidities, limited hospitalization, and intensive care capacity may increase this risk.
Fuller DH, Berglund P. Amplifying RNA Vaccine Development. NEJM, June 18, 2020. N Engl J Med 2020; 382:2469-2471. Full-text: https://doi.org/10.1056/NEJMcibr2009737
Recent interest in messenger RNA (mRNA) vaccines has been fueled by methods that increase mRNA stability and protein production and improve delivery. The mRNA vaccines do not need to enter the nucleus to express the antigen. Avoidance of the risk of integration into the host genome is thus considered a comparative advantage. The authors describe new techniques in this field. The most promising seems to be a strategy that is based on two RNA vectors — one retaining the replicase-encoding gene and the other encoding the antigen.
Huo J, Zhao Y, Ren J, et al. Neutralisation of SARS-CoV-2 by destruction of the prefusion Spike. Cell Host Microbe June 19, 2020. Full-text: https://doi.org/10.1016/j.chom.2020.06.010
The monoclonal antibody CR3022 tightly binds the receptor binding domain (RBD) and neutralizes SARS-CoV-2. The highly conserved, structure-stabilising, CR3022 epitope is inaccessible in the prefusion Spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. The mechanism of neutralisation is new and was not seen before for coronaviruses, suggesting that the CR3022 epitope should be a major target for therapeutic antibodies.
Sardanelli D, Cozzi A, Monfardini L, et al. Association of mediastinal lymphadenopathy with COVID-19 prognosis. Lancet Inf Dis June 19, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30521-1
Among 410 patients with COVID-19 who underwent CT at emergency department admission in three hospitals in Lombardy, Italy, 76 (19%) patients had mediastinal lymphadenopathies (ie, lymph nodes with a short-axis diameter > 1 cm). Data suggest that lymphadenopathy may be considered a predictor of a worse outcome. The pathophysiological meaning of this finding remains to be investigated.
Fosbøl EL, Butt JH, Østergaard L, et al. Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality. JAMA June 19, 2020. Full-text: https://doi.org/10.1001/jama.2020.11301
ACE inhibitors are not harmful, even in Denmark (one of the countries with the best epidemiological data). In a retrospective cohort study of 4,480 (!) patients diagnosed as having COVID-19, prior ACEI/ARB use, compared with no use, was not significantly associated with mortality (adjusted hazard ratio, 0.83). In a nested case-control study of a cohort of 494,170 patients with hypertension, use of ACEI/ARB, compared with use of other antihypertensive medications, was not significantly associated with COVID-19 diagnosis (adjusted hazard ratio, 1.05).
Lai PH, Lancet EA, Weiden MD. Characteristics Associated With Out-of-Hospital Cardiac Arrests and Resuscitations During the Novel Coronavirus Disease 2019 Pandemic in New York City. JAMA Cardiol. Published online June 19, 2020. Full-text: https://doi.org/10.1001/jamacardio.2020.2488
In this population-based cross-sectional study of 5,325 patients with out-of-hospital cardiac arrests in New York City, the number undergoing resuscitation was 3-fold higher during the COVID-19 period compared with the similar period in 2019. The authors report 2,653 excess out-of-hospital cardiac arrests (90% of these excess cases resulted in out-of-hospital deaths).
Koopmann A, Ekaterini G, Falk K, et al. Did the General Population in Germany Drink More Alcohol during the COVID-19 Pandemic Lockdown? Alcohol and Alcoholism, June 19 20020. Full-text: https://doi.org/10.1093/alcalc/agaa058
Question of the day. Answer: Some did so, yes. Out of the 2,102 participants of this survey, 34.7% reported drinking “more or much more” alcohol since the begin of the lockdown. Binary logistic regression analyses showed that especially low educated subjects and subjects with higher levels of perceived stress due to the lockdown were at risk of consuming more alcohol during the lockdown.
Cappo A, Bellani G, Wintertin D, et al. Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study. Lancet Resp Med June 19, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30268-X
This prospective cohort study enrolled 56 patients with COVID-19-related pneumonia receiving supplemental oxygen or non-invasive continuous positive airway pressure. Prone positioning was feasible in most patients and effective in rapidly ameliorating blood oxygenation. The effect was maintained after resupination in half of the patients.
Robbiani DF, Gaebler C, Muecksch F et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature 2020. https://doi.org/10.1038/s41586-020-2456-9
This may help to explain why convalescent plasma does not work in all patients. In plasma from 149 patients collected an average of 39 days after the onset of symptoms, neutralizing titres were extremely variable. Most plasmas did not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
Clementi N, Ferrarese R, Criscuolo E, et al. Interferon-β 1a inhibits SARS-CoV-2 in vitro when administered after virus infection. J Inf Dis, June 19 2020. Full-text: https://doi.org/10.1093/infdis/jiaa350
IFN may work, when given early. Several clinical trials into the administration of IFN to COVID-19 patients are currently ongoing. These in vitro observations shed light for the first time on antiviral activity of IFN-β1a against SARS-CoV-2 when administered after the infection of cells, highlighting its possible efficacy in an early therapeutic setting.