Hui KPY, Cheung MC, Perera RAPM, et al. Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures. Lancet Respir Med. 2020 May 7. pii: S2213-2600(20)30193-4. PubMed: https://pubmed.gov/32386571. Full-text: https://doi.org/10.1016/S2213-2600(20)30193-4
More insights into transmissibility and pathogenesis. Using ex-vivo cultures, authors evaluated tissue and cellular tropism of SARS-CoV-2 in the human respiratory tract and conjunctiva in comparison with other coronaviruses. In the bronchus and in the conjunctiva, SARS-CoV-2 replication competence was higher than SARS-CoV. In the lung, it was similar to SARS-CoV but lower than MERS-CoV.
Corey L, Mascola JR, Fauci AS, Collins FS. A strategic approach to COVID-19 vaccine R&D. Science Policy Forum, May 11, 2020. Full-text https://science.sciencemag.org/content/early/2020/05/08/science.abc5312
The full development pathway for an effective vaccine for SARS-CoV-2 will require that industry, government, and academia collaborate in unprecedented ways, each adding their individual strengths. Authors discuss one such collaborative program that has recently emerged: the ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) public-private partnership.
Bost P, Giladi A, Liu Y, et al. Host-viral infection maps reveal signatures of severe COVID-19 patients. Cell May 07, 2020. Full-text: https://doi.org/10.1016/j.cell.2020.05.006
A computational method is proposed that globally scans unmapped scRNA-seq data for the presence of viral RNA, enabling transcriptional cell sorting of infected versus bystander cells. It is shown how SARS-CoV-2 infects epithelial cells and alters the immune landscape in patients with severe disease.
Li H, Liu L, Zhang D, et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet. 2020 May 9;395(10235):1517-1520. PubMed: https://pubmed.gov/32311318. Full-text: https://doi.org/10.1016/S0140-6736(20)30920-X
Brief but nice review and several hypotheses about SARS-CoV-2 pathogenesis. What happens during the second week – when resident macrophages initiating lung inflammatory responses are unable to contain SARS-CoV-2 infection and when both innate and adaptive immune responses are insufficient to curb the viral replication and the patient doesn’t recover quickly.
Menni, C., Valdes, A.M., Freidin, M.B. et al. Real-time tracking of self-reported symptoms to predict potential COVID-19. Nat Med 2020, May 11. https://doi.org/10.1038/s41591-020-0916-2
A total of 18,401 participants from US/UK reported potential symptoms on a smartphone app and underwent a SARS-CoV-2 test. The proportion of participants who reported loss of smell and taste was higher in those with a positive test result (65% vs 22%). A combination of symptoms, including anosmia, fatigue, persistent cough and loss of appetite was appropriate to identify individuals with COVID-19.
Teufel M, Schweda A, Dörrie N. Not all world leaders use Twitter in response to the COVID-19 pandemic: impact of the way of Angela Merkel on psychological distress, behaviour and risk perception. Journal of Public Health May 12, 2020. Full-text: https://academic.oup.com/jpubhealth/advance-article/doi/10.1093/pubmed/fdaa060/5835923
By no doubt the weirdest paper title of the day. In a large online survey, the authors determined the levels of COVID-19 fear, anxiety and depression in 12,244 respondents during two weeks in March. Concurrent with Angela Merkel’s speech on March 16, a reduction of anxiety and depression was noticeable in the German population.
Kandemirli SG, Dogan L, Sarikaya ZT, et al. Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection. Radiology. 2020 May 8:201697. PubMed: https://pubmed.gov/32384020. Full-text: https://doi.org/10.1148/radiol.2020201697
A brain MRI was performed in 27/50 patients with neurologic symptoms. The most common imaging finding was cortical signal abnormalities on FLAIR images (10/27, 37%), accompanied by cortical diffusion restriction or leptomeningeal enhancement. However, the complex clinical course including comorbidities, long ICU stay with multidrug regimens, and respiratory distress with hypoxia episodes can all act as confounding factors – a clear cause-effect relationship between COVID-19 infection and MRI findings will be hard to establish.
Hung FN, Lung KC, Tso EY, et al. Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet May 08, 2020. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31042-4/fulltext
Some evidence that interferon may be helpful, when given during the first week: this Phase II, multicentre, open-label trial from Hong Kong randomized 127 patients with mild-to-moderate COVID-19 (median 5 days from symptom onset) to receive lopinavir/r only or a triple combination. Triple therapy was given only to patients with less than 7 days from symptom onset and consisted of lopinavir/r, ribavirin (400 mg BID), and interferon beta-1b (1-3 doses of 8 Mio IE per week). Combination therapy led to a significantly shorter median time to negative results in nasopharyngeal swab (7 versus 12 days, p=0.001) and other specimens. Clinical improvement was significantly better, with a shorter time to complete alleviation of symptoms and a shorter hospital stay. Of note, all differences were driven by the 76 patients who started treatment less than 7 days after onset of symptoms.
Martin-Blondel G, Ruiz S, Murris M, et al. Hydroxychloroquine in COVID-19 patients: what still needs to be known about the kinetics. Clin Infect Dis. 2020 May 11. PubMed: https://pubmed.gov/32392332. Full-text: https://doi.org/10.1093/cid/ciaa558
Different dosage regimens of hydroxychloroquine are currently used to manage COVID-19. The concentrations measured in 57 patients showed that hydroxychloroquine exposure was relatively low and in most instances lower than the values reported in systemic lupus erythematosus patients, in particular for the standard regimen of 200 mg TID. A full hydroxychloroquine kinetic exploration is needed.
Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020 May 7. PubMed: https://pubmed.gov/32386565. Full-text: https://doi.org/10.1016/S0140-6736(20)31094-1
Unprecedented cluster of eight children (all previously fit and well) with hyperinflammatory shock, showing features similar to atypical Kawasaki disease, Kawasaki disease shock syndrome, or toxic shock syndrome. Two children (one died) were positive for SARS-CoV-2 and four children had a known family exposure to COVID-19. This case cluster formed the basis of a national alert.