The COVID-19 Curator
Your roundup of the key scientific studies and industry announcements emerging from the pandemic
The COVID-19 Curator – a weekly newsletter – curates the top scientific news from the pandemic and delivers it straight to your inbox every Friday. You can sign up at: www.texerenewsletters.com/covid19newsletter
In this feature, we roundup the latest and greatest research studies and company announcements made over the course of the last month (May 8 to June 5).
Industry news
EMA. The EMA has raised concerns about the number of independent COVID-19 trials with few participants – and calls for resources to be pooled into larger multi-arm trials. Authors from the agency have written an article setting out “concrete actions” that stakeholders involved with COVID-19 clinical trials should take to generate the type of conclusive evidence needed to enable rapid development and approval of potential treatments and vaccines. H-G Eichler et al., “Clinical trials for Covid‐19: can we better use the short window of opportunity?” Clinical Pharmacology & Therapeutics (2020).
Gilead. The FDA has granted emergency authorization to Gilead’s remdesivir to treat COVID-19 patients – despite it not being approved yet for any indication. Remdesivir inhibits viral RNA synthesis, with Gilead’s recent Phase III trial showing that five-day treatment of remdesivir results in greater clinical improvements compared with standard care alone. Various other studies are also emerging to highlight the potential of remdesivir. EMA has commenced a “rolling review” of data in Europe.
Moderna. Reporting positive interim Phase I data for its investigational mRNA vaccine (mRNA-1273) against COVID-19, the company aims to start a Phase III study in July. The study was led by the US National Institute of Allergy and Infectious Diseases (NIAID).
Eli Lilly. A Phase I study has commenced for LY-CoV555 – a neutralizing IgG1 monoclonal antibody designed to block COVID-19 viral attachment and entry into human cells. The antibody was developed in collaboration with AbCellera. AbCellera and the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases identified the antibody in a blood sample taken from a patient who recovered from the virus.
AstraZeneca. AstraZeneca and the UK’s University of Oxford are collaborating on an adenovirus-based vaccine (AZD1222) that entered trials in April. AstraZeneca has already signed a clinical and commercial supply agreement with Oxford Biomedica and committed to deliver millions of doses, including 100 million doses for Britain and 300 million for the US.
Sinovac Biotech. Preclinical results for CoronaVac show it is safe and efficacious in rhesus macaques. The company is also building a vaccine facility capable of manufacturing up to 100 million doses of the vaccine annually.
Catalent. Catalent will develop a powder-in-capsule formulation of Ennaid’s ENU200, which is a repurposed oral antiviral drug. Ennaid selected ENU200 after an in silico bioinformatic search identified that the chemical compounds may block the spike-S glycoprotein and the key coronavirus enzyme, Mpro.
Early research
Of mice and mAbs. A fully human monoclonal antibody shows success in cell culture by targeting a communal epitope on SARS-CoV-2 that could prevent the virus from infecting human cells. The mAb was identified by researchers from Utrecht University, the Erasmus Medical Center, and Harbour BioMed, using Harbour BioMed’s H2L2 transgenic mouse technology. The researchers have previously done work on antibodies targeting SARS-CoV. C Wang et al., “A human monoclonal antibody blocking SARS-CoV-2 infection,” 11 (2020).
A little help from llamas. A unique type of antibody present in llamas and other camelids is found to bind to the SARS-CoV-2 spike protein and interfere with receptor binding, preventing the virus from infecting cells. Researchers from the University of Texas at Austin, the National Institutes of Health, and Ghent University linked two copies of an antibody produced by llamas. They hope to develop a treatment that could help soon after a person is infected. D Wrapp et al., “Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies,” Cell, 181, 1004-1015 (2020).
Blast from the past. Antibody first identified from recovered SARS patient in 2003 – S309 – is shown to neutralize SARS-CoV-2 and SARS-CoV pseudoviruses. The senior authors of the paper are David Veesler (assistant professor of biochemistry at the University of Washington School of Medicine) and Davide Corti Humabs (Chief Scientific Officer at Humabs Biomed SA, a subsidiary of Vir Biotechnology). Veesler’s lab has been studying infectious diseases, including coronaviruses, for a number of years. The antibody has been fast tracked for development at VIR Biotechnology. D Pinto et al., “Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody,” Nature (2020).
Cell therapy opportunity. Could cell-based therapies have a role to play against COVID-19? With some data suggesting mesenchymal stem (stromal) cells could help treat lung injury resulting from respiratory viruses, authors explore the applicability of cell-based therapies to COVID-19. They also stress that the industry must take a “strong stance” against stem cell clinics offering unproven cell therapies for COVID-19. M Khoury et al., “Current Status of Cell-Based Therapies for Respiratory Virus Infections: Applicability to COVID-19,” European Respiratory Journal, 55 (2020).
Other avenues
Quitting chloroquine. A recent study and a systematic review have shown no benefit from the use of chloroquine or hydroxychloroquine as COVID-19 treatment or prophylaxis. Additionally, the WHO has halted trials of the drugs due to the risk of harm. MR Mehra et al., “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis,” The Lancet (2020); AV Hernandez et al., “Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review,” Annals of Internal Medicine (2020).
Shortened shedding. Interferon-α2b has been shown to shorten duration of viral shedding by around seven days and to reduce levels of inflammatory proteins in COVID-19 patients. Q Zhou et al., “Interferon-α2b Treatment for COVID-19,” Frontiers in Immunology (2020).
Vitamin D consensus. High doses of vitamin D are not effective in preventing or treating COVID-19, but some evidence suggests low vitamin D levels are associated with other acute respiratory tract infections. SA Lanham-New et al., “Vitamin D and SARS-CoV-2 virus/COVID-19 disease,” BMJ Nutrition, Prevention & Health (2020).
Moonshot medicines. Computational screening has identified two approved anti-inflammatory drugs that inhibit replication of COVID-19 virus; the work has been validated in in vitro studies by COVID Moonshot. A Gimeno et al., “Prediction of Novel Inhibitors of the Main Protease (M-pro) of SARS-CoV-2 through Consensus Docking and Drug Reposition,” International Journal of Molecular Sciences, 20, 3793 (2020).
Taking stock. Researchers have created a database that tracks and categorizes off-label drug use worldwide for COVID-19. The database should help identify treatments for further clinical study – for both COVID-19 and other diseases. DC Fajgenbaum et al., “Treatments Administered to the First 9152 Reported Cases of COVID-19: A Systematic Review,” Infectious Diseases and Therapy (2020).
Invisible enemy. Aerosols exhaled by asymptomatic individuals may be responsible for a large proportion of COVID-19 spread, highlighting the importance of masks and social distancing. KA Prather, CC Wang, RT Schooley, “Reducing transmission of SARS-CoV-2,” Science (2020).
Understanding COVID-19
Starting early. Testing on a sample collected from a French ICU patient in December 2019 showed that SARS-CoV-2 was present in the country a month earlier than suspected, suggesting that pandemic outcome models may not be accurate. A Deslandes et al., “SARS-CoV-2 was already spreading in France in late December 2019,” International Journal of Antimicrobial Agents (2020).
Silent majority? A study of a group of isolated cruise ship passengers revealed that eight in 10 people testing positive exhibited no symptoms – a result with worrying implications for contact tracing and self-isolation approaches to infection control. AJ Ing, C Cocks, JP Green, “COVID-19: in the footsteps of Ernest Shackleton,” Thorax (2020).
Infection and immunity. A review summarizes what we know so far about coronavirus diseases, such as SARS and MERS, our current understanding of SARS-CoV-2, and where research is most urgently needed to address the current pandemic. P Kellam, W Barclay, “The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection,” Journal of General Virology (2020).
Double whammy. People carrying two faulty copies of the APOE gene (which is linked to increased risk of Alzheimer's and heart disease) face double the risk of severe COVID-19 – irrespective of pre-existing dementia or cardiovascular disease. C-L Kuo et al., “APOE e4 genotype predicts severe COVID-19 in the UK Biobank community cohort,” The Journals of Gerontology: Series A (2020).
Mutational analysis. Human deaminase enzymes, which edit SARS-CoV-2 RNA, may play a role in both the evolution of the virus and the spread of infection. S Di Giorgio et al., “Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2,” Science (2020).
Weakened defense. MicroRNAs that attack viruses diminish with old age and chronic health problems, which helps explain why those populations are especially vulnerable to COVID-19. F Sadanand et al, “COVID-19 Virulence in Aged Patients Might Be Impacted by the Host Cellular MicroRNAs Abundance/Profile,” Aging and Disease, 11, 509-522 (2020).
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