Shi J, Wen Z, Zhong G, et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science. 2020 Apr 8. pii: science.abb7015. PubMed: https://pubmed.gov/32269068 . Full-text: https://doi.org/10.1126/science.abb7015
SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks. However, ferrets and cats are permissive to infection and cats were susceptible to airborne infection. But cat owners may relax. Experiments were done in a small number of cats exposed to high doses of the virus, probably not representing real-life. It remains also unclear if cats secret enough coronavirus to pass it on to people.
Wang X, Xu W, Hu G, et al. SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion. Cell Mol Immunol. 2020 Apr 7. pii: 10.1038/s41423-020-0424-9. PubMed: https://pubmed.gov/32265513 . Full-text: https://doi.org/10.1038/s41423-020-0424-9
It remains unclear whether SARS-CoV-2 can also infect T cells, resulting in lymphocytopenia. Using a model with pseudoviruses, authors showed that SARS-CoV-2 infects (but does not replicate in) T cells through S protein-mediated membrane fusion. T-cell lines were significantly more sensitive to SARS-CoV-2 infection when compared with SARS-CoV. Of note, a very low expression level of hACE2 was found, indicating that a novel receptor might mediate SARS-CoV-2 entry into T cells.
Le TT, Andreadakis Z, Kumar A, et al. The COVID-19 vaccine development landscape. Nature reviews drug discovery. 09 April 2020. doi: 10.1038/d41573-020-00073-5. Full-text: https://www.nature.com/articles/d41573-020-00073-5
Brief data-driven overview by seven experts. The conclusion is that efforts are unprecedented in terms of scale and speed and that there is an indication that vaccine could be available by early 2021. As of 8 April 2020, the global vaccine landscape includes 115 candidates, of which the 5 most advanced candidates have already moved into clinical development, including mRNA-1273 from Moderna, Ad5-nCoV from CanSino Biologicals, INO-4800 from Inovio, LV-SMENP-DC and pathogen-specific aAPC from Shenzhen Geno-Immune Medical Institute. The race is on!
Xu K, Chen Y, Yuan J, et al. Factors associated with prolonged viral RNA shedding in patients with COVID-19. Clin Infect Dis. 2020 Apr 9. pii: 5818308. PubMed: https://pubmed.gov/32271376 . Full-text: https://doi.org/10.1093/cid/ciaa351
In a cohort of 113 symptomatic patients from two hospitals outside Wuhan, the median duration of SARS-CoV-2 RNA detection was 17 days (IQR, 13-22 days) as measured from illness onset. Male sex, delayed hospital admission, and invasive mechanical ventilation were independent risk factors for prolonged SARS-CoV-2 RNA shedding.
Okba NMA, Muller MA, Li W, et al. Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease 2019 Patients. Emerg Infect Dis. 2020 Apr 8;26(7). PubMed: https://pubmed.gov/32267220 . Full-text: https://doi.org/10.3201/eid2607.200841
Small study, demonstrating that most PCR-confirmed SARS-CoV-2-infected persons seroconverted by 2 weeks after disease onset. Sensitivity varied between the assays (IgA ELISA showed higher sensitivity). It remains crucial to calibrate and standardize assays developed by different laboratories by using well-defined standard references as part of diagnostic assay validation.
Wang Y, Lu X, Chen H, et al. Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19. Am J Respir Crit Care Med. 2020 Apr 8. PubMed: https://pubmed.gov/32267160 . Full-text: https://doi.org/10.1164/rccm.202003-0736LE
Large single-center case series study on 344 severe and critically ill patients admitted to Tongji hospital from January 25 through February 25, 2020. Of all, 133 (38.7%) patients died at a median of 15 days. Beside older age, hypertension and COPD were more common in non-survivors but not diabetes. No difference was seen between patients with or without ACE inhibitors.
Ji D, Zhang D, Xu J, et al. Prediction for Progression Risk in Patients with COVID-19 Pneumonia: the CALL Score. Clin Infect Dis. 2020 Apr 9. pii: 5818317. PubMed: https://pubmed.gov/32271369. Full-text: https://doi.org/10.1093/cid/ciaa414
CURB-65 severity score may not be suitable for COVID-19. In 208 patients, a risk factors scoring system was developed, for prediction of progression, based on patients’ age, comorbidities, lymphocyte count and serum LDH at presentation. Needs to be validated by larger studies.
Grein J, Ohmagari N, Shin D, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med. 2020 Apr 10. PubMed: https://pubmed.gov/32275812 . Full-text: https://doi.org/10.1056/NEJMoa2007016
A compassionate use program of remdesivir for patients with severe COVID-19 is described. Clinical improvement was observed in 36/53 (68%) patients. Since published yesterday, data are celebrated in the media. Unjustifiably. Although authors have made some efforts to discuss their data carefully, even more caution is needed. We believe that with this “study”, any (yes, any!) clinical benefit of remdesivir remains unproven. Moreover, several issues in this data set seem to be very implausible. We have written a correspondence letter to NEJM and keep you updated.
Sheahan TP, Sims AC, Zhou S, et al. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci Transl Med. 2020 Apr 6. pii: scitranslmed.abb5883. PubMed: https://pubmed.gov/32253226 . Full-text: https://doi.org/10.1126/scitranslmed.abb5883
The ribonucleoside analog beta-D-N(4)-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against all CoVs, as well as increased potency against resistance mutations to the nucleoside analog inhibitor remdesivir. But how long will it take to bring this compound into clinical trials?
Jin Z, Du X, Xu Y, et al. Structure of M(pro) from COVID-19 virus and discovery of its inhibitors. Nature. 2020 Apr 9. pii: 10.1038/s41586-020-2223-y. PubMed: https://pubmed.gov/32272481 . Full-text: https://doi.org/10.1038/s41586-020-2223-y
Virtual drug screening to identify new drug leads that target the COVID-19 virus main protease M(pro) which plays a pivotal role in mediating viral replication and transcription. Six compounds inhibited M(pro) with IC50 values ranging from 0.67 to 21.4 muM, among them with disulfiram and carmofur (a pyrimidine analogue used as an antineoplastic agent) two approved drugs.