Copy-editor: Rob Camp
Virology
Miao G, Zhao H, Li Y, et al. ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-mediated assembly of the SNARE complex required for autolysosome formation. Development Cell December 16, 2020. Full-text: https://doi.org/10.1016/j.devcel.2020.12.010
Have no clue what HOPS and SNARE complexes are? Never mind. Autophagy acts as a cellular surveillance mechanism to combat invading pathogens. Viruses have evolved various strategies to block autophagy and even subvert it for their replication and release. This study reveals a mechanism by which SARS-CoV-2 evades lysosomal destruction. ORF3a, an accessory protein specific to SARS-CoV-2, greatly impairs the formation of degradative autolysosomes.
Liu K, Tan S, Niu S, et al. Cross-species recognition of SARS-CoV-2 to bat ACE2. PNAS December 16, 2020. 118 (1). Full-text: https://doi.org/10.1073/pnas.2020216118
SARS-CoV-2 may infect bats, and the extensive species diversity of bats may have profound effects on SARS-CoV-2 evolution. However, SARS-CoV-2 receptor binding domain (RBD) binds to bACE2-Rm with lower affinity than that to human ACE2 receptor (hACE2).
Immunology
Yao C, Bora SA, Patimo T, et al. Cell type-specific immune dysregulation in severely ill COVID-19 patients. Cell Report December 16, 2020. Full-text: https://doi.org/10.1016/j.celrep.2020.108590
Changfu Yao and colleagues have added some evidence to the observation that although most immune cellular compartments have an expected hyper-inflammatory response in severe patients, several of their key pathways are dysfunctional. Moreover, immune imbalance in which dysregulation of both the innate and adaptive immune responses may be contributing to a more severe disease course. The key findings: monocyte antigen presentation pathway gene expression is lower in severe COVID-19, lymphocyte cytotoxicity pathways are reduced, and B cell activation is blunted. Interferon signaling is elevated in lymphocytes but diminished in monocytes.
Keller MD, Harris KM, Jensen-Wachspress MA, et al. SARS-CoV-2–specific T cells are rapidly expanded for therapeutic use and target conserved regions of the membrane protein. Blood December 17, 2020, 136 (25): 2905–2917. Full-text: https://doi.org/10.1182/blood.2020008488
In this report, Michael Keller and colleagues demonstrate a broadly specific T cell therapeutic targeting 3 structural proteins of SARS-CoV-2 that could be reliably expanded from the majority of convalescent donors. The authors believe that SARS-CoV-2 directed T cell immunotherapy targeting structural proteins (most importantly the membrane protein) should be feasible for the prevention or early treatment of SARS-CoV-2 infection in immunocompromised patients with blood disorders.
Vaccine
Editorial. COVID-19 vaccines: the pandemic will not end overnight. The Lancet Microbe December 18, 2020. Full-text: https://doi.org/10.1016/S2666-5247(20)30226-3
See title. Even a global mass immunization program will not immediately end the COVID-19 pandemic. Although control over the infection’s most harmful effects is expected and limiting its spread can be hoped for, it will likely be a few years before the virus can be brought under control worldwide.
Prevention
Priesemann V, Brinkmann MM, Ciesek S, et al. Calling for pan-European commitment for rapid and sustained reduction in SARS-CoV-2 infections. Lancet December 18, 2020. Full-text: https://doi.org/10.1016/S0140-6736(20)32625-8
In their comment (which was signed by > 200 researchers), the authors urge governments throughout Europe to agree on clearly formulated common goals, coordinate their efforts, develop regionally adapted strategies to reach the goals, and thereby work resolutely towards lowering case numbers.
Clinical
Woolf SH, Chapman DA, Lee JH. COVID-19 as the Leading Cause of Death in the United States. JAMA December 17, 2020. Full-text: https://doi.org/10.1001/jama.2020.24865
The news media dutifully report each day’s increase in new cases and deaths but putting these numbers in perspective may be difficult. According to CDC data, by October 2020, COVID-19 had become the third leading cause of death for persons aged 45 through 84 years and the second leading cause of death for those aged 85 years or older. Adults 45 years or older were more likely to die from COVID-19 than from chronic lower respiratory disease, transport accidents (eg, motor vehicle fatalities), drug overdoses, suicide, or homicide. Steven H. Woolf and colleagues argue that the daily US mortality rate for COVID-19 deaths is equivalent to the September 11 attacks, which claimed 2988 lives, occurring every 1.5 days, or 19 Airbus 320 jetliners, each carrying 150 passengers, crashing every day.
Comorbidities
ERA-EDTA Council, ERACODA Working Group. Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA. Nephrology Dialysis Transplantation December 19 2020. Full-text: https://academic.oup.com/ndt/advance-article/doi/10.1093/ndt/gfaa314/6041849
The OpenSAFELY project analysed factors associated with COVID-19 deaths in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death, but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR < 30 mL/min/1.73 m2) represent three of the four co-morbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is higher than the risk associated with diabetes mellitus (aHR range 1.31–1.95, depending upon glycemic control) or chronic heart disease (aHR 1.17). This article defines essential action points, among which is advocating the inclusion of CKD patients in clinical trials, testing the efficacy of drugs and vaccines to prevent severe COVID-19.
Treatment
Salama C, Han J, Yau L, et al. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. NEJM December 17. Full-text: https://doi.org/10.1056/NEJMoa2030340
In this RCT, 389 patients hospitalized with COVID-19 pneumonia who were not receiving mechanical ventilation were randomized to receive standard of care plus one or two doses of either tocilizumab (TCZ) or placebo. TCZ reduced the likelihood of progression to the composite outcome of mechanical ventilation or death (12% vs 19%), but it did not improve survival.
Dal-Ré R, Banzo R, Georgin-Lavialle S, et al. Remdesivir for COVID-19 in Europe: will it provide value for money? Lancet Resp Med December 17, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30568-3
In their comment on remdesivir pricing, Rafael Dal-Ré and colleagues review the clinical data available and argue that once remdesivir becomes available in Europe, governments should agree a substantially lower price with Gilead (amid a time of high incidence of COVID-19 cases in Europe, and with remdesivir in short supply, the European Commission had signed a joint procurement contract with Gilead, with an agreed price of $2340 for a 5-day course). Until the effectiveness of remdesivir in clinical practice is well defined in Europe, a pay-for-result agreement might also be considered.