Top 10: April 14

<<< April 2020

By Christian Hoffmann &
Bernd S. Kamps

Virology

Monteil V, Kwon H, Patricia Prado P, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 2020. DOI: 10.1016/j.cell.2020.04.004. https://www.cell.com/pb-assets/products/coronavirus/CELL_CELL-D-20-00739.pdf

This study shows that human recombinant soluble ACE2 (hrsACE2) blocks SARS-CoV-2 infections of different cells, human blood vessel organoids and human kidney organoids. In ARDS patients, hrsACE2 was ineffective but safe at a broad range of doses. Apeiron Biologics plans a randomized study on 200 COVID-19 patients in April.

 

Epidemiology

van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020 Mar 17. PubMed: https://pubmed.gov/32182409 . Full-text: https://doi.org/10.1056/NEJMc2004973

This important work had been published a few weeks ago. Today, no less than 6 correspondence letters mainly discuss airborne transmission and viability of SARS-CoV-2 in aerosols. Bottom line: Viability was investigated under experimental conditions and should not be used to draw conclusions about airborne transmission. However, according to the authors, aerosol-generating medical procedures should be examined as well as decontamination techniques.

 

Sutton D, Fuchs K, D´Alton M, Goffman D. Universal Screening for SARS-CoV-2 in Women Admitted for Delivery. N Engl J Med. 2020 Apr 13. PubMed: https://pubmed.gov/32283004. Full-text: https://doi.org/10.1056/NEJMc2009316

Between March 22 and April 4, 2020, all pregnant women who delivered infants were tested in a hospital located on the northern tip of Manhattan, New York City. Nasopharyngeal swabs obtained from 210 asymptomatic women were positive in 29 (13.7%). All four women with symptoms of Covid-19 on admission were positive. In other words: 29/33 women were asymptomatic.

 

Kong WH, Li Y, Peng MW, et al. SARS-CoV-2 detection in patients with influenza-like illness. Nat Microbiol. 2020 Apr 7. pii: 10.1038/s41564-020-0713-1. PubMed: https://pubmed.gov/32265517 . Full-text: https://doi.org/10.1038/s41564-020-0713-1

Re-analysing 640 throat swabs collected from patients in Wuhan with influenza-like-illness from 6 October 2019 to 21 January 2020, authors found 9 to be positive for SARS-CoV-2. The onset date of the earliest case was 4 January 2020, one week after the outbreak was reported by hospitals.

 

Clinical

Zini G, Bellesi S, Ramundo F, d´Onofrio G. Morphological anomalies of circulating blood cells in COVID-19. Am J Hematol. 2020 Apr 12. PubMed: https://pubmed.gov/32279346 . Full-text: https://doi.org/10.1002/ajh.25824

Morphologic changes in the peripheral blood over time in a few COVID-19 patients from Italy. In the early phase of symptom aggravation, a pronounced granulocytic reaction with immaturity, dysmorphism and apoptotic-degenerative morphological evidence was seen. Later the hematologic pictures tended to shift toward impressive reactive lymphocyte activation, often with numerical increase, and heterogeneous morphological expression. 

 

Comorbidities

Wang H, Li T, Barbarino P, et al. Dementia care during COVID-19. Lancet. 2020 Apr 11; 395(10231):1190-1191. PubMed: https://pubmed.gov/32240625 . Full-text: https://doi.org/10.1016/S0140-6736(20)30755-8

A few thoughts on dementia care in this crisis.

 

Treatment

De Meyer S, Bojkova D, Cinati J, et al. Lack of Antiviral Activity of Darunavir against SARS-CoV-2. doi: https://doi.org/10.1101/2020.04.03.20052548

Usually we hesitate to refer to www.medrxiv.org. Preprints published at this website are preliminary reports of work that have not been certified by peer review. Well, it’s time to make an exception. Because this is important: Darunavir, an HIV protease inhibitor, is not active against SARS-CoV-2. There was no vitro antiviral activity against a clinical isolate at clinically relevant concentrations (EC50 >100 μM). Remdesivir, used as a positive control, showed potent activity (EC50 = 0.38 μM). However, the clinical trial on 3.040 participants treated with darunavir in Spain is still ongoing (clintrials.gov assessed on April 13).

 

Bartiromo M, Borchi B, Botta A, et al. Threatening drug-drug interaction in a kidney transplant patient with Coronavirus Disease 2019 (COVID-19). Transpl Infect Dis. 2020 Apr 12. PubMed: https://pubmed.gov/32279418 . Full-text: https://doi.org/10.1111/tid.13286

If you give HIV PIs, please be always aware of drug-drug interactions. Ritonavir is a strong pharmacoenhancer. For example, tacrolimus has to be reduced by 10-100 fold to maintain concentration within the therapeutical range. In this case report, a women with kidney transplantation  was treated with lopinavir/r (the “r” indicates ritonavir) for COVID-19 while receiving the full dose tacrolimus. Levels went incredibly high and were still above the therapeutical range, 9 days after stopping both lopinavir/r and tacrolimus. Fortunately, everything turned out alright.

 

Feldmann M, Maini RN, Woody JN, et al. Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed. Lancet. 2020 Apr 9. pii: S0140-6736(20)30858-8. PubMed: https://pubmed.gov/32278362 . Full-text: https://doi.org/10.1016/S0140-6736(20)30858-8

Treating the inflammatory excess in patients with COVID-19: Why anti-tumour necrosis factor (TNF) antibodies could be a good idea.

 

McEnery T, Gough C, Costello RW. COVID-19: Respiratory support outside the intensive care unit. Lancet Respir Med. 2020 Apr 9. pii: S2213-2600(20)30176-4. PubMed: https://pubmed.gov/32278367 . Full-text: https://doi.org/10.1016/S2213-2600(20)30176-4

The debate about the optimal mode of respiratory support (outside ICU) continues. Advocate high flow nasal cannulae (HFNC) over non-invasive ventilation (NIV) or vice versa? In the absence of randomised control trials in the use of either HFNC or NIV in COVID-19, this comment discusses current knowledge.