Copy-editor: Rob Camp
Epidemiology
Taylor CA, Boulos C, Almond D. Livestock plants and COVID-19 transmission. PNAS November 19, 2020. Full-text: https://doi.org/10.1073/pnas.2010115117
Livestock processing poses a particular public health risk extending far beyond meatpacking companies and their employees. The authors estimate livestock plants to be associated with 236.000 to 310.000 COVID-19 cases (6 to 8% of total US cases) and 4300 to 5.200 deaths (3 to 4% of total US cases) as of July 21. They also illustrate potential contributions of plant size, industrial concentration, plant shutdowns, and policy actions to this phenomenon. High numbers were found among large processing facilities and large meatpacking companies. According to the authors, their results “motivate investigation into supply chains, operating procedures, and labor relations within the meatpacking industry”. They also discuss some implications. Interestingly, one was seemingly beyond the intellectual grasp of the authors: that consumers could abstain from buying meat produced by these large meatpacking companies.
Virology
Hammer AS, Quaade ML, Rasmussen TB, Fonager J, Rasmussen M, Mundbjerg K, et al. SARS-CoV-2 transmission between mink (Neovison vison) and humans, Denmark. Emerg Infect Dis Nov 18, 2020. 2021 Feb. Full-text: https://doi.org/10.3201/eid2702.203794
Anne Sophie Hammer and colleagues describe the outbreaks on three Danish mink farms. A high proportion of mink were infected within a few days, which may provide major virus exposure to persons working with mink. Full-length virus genome sequencing revealed novel viral variants in mink. These variants subsequently appeared within the local human community.
Immunology
Karki ER, Sharma BR, Tuladhar S, et al. Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell November 18, 2020. Full-text: https://doi.org/10.1016/j.cell.2020.11.025
More on the cytokine storm: Rajenda Karki and colleagues evaluated the role of pro-inflammatory cytokines that are highly upregulated in patients with COVID-19 in inducing inflammatory cell death, inflammation, tissue and organ damage, and mortality. They show that the specific combination of TNF-α and IFN-γ is critical for these processes. In mice, the combination of anti-TNF-α and anti-IFN-γ neutralizing antibodies protected against death in SARS-CoV-2 infection and models of sepsis, hemophagocytic lymphohistiocytosis (HLH), and cytokine shock.
Hekman RM, Hume AJ, Goel RK, et al. Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2. Molecular Cell November 18, 2020. Full-text: https://doi.org/10.1016/j.molcel.2020.11.028
SARS-CoV-2 infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange. As AT2 injury is central to COVID-19 pathogenesis, there is an urgent need to delineate the mechanisms of SARS-CoV-2-driven lung pathology. Primary AT2s are difficult to maintain in culture, but human induced pluripotent stem cell-derived alveolar epithelial type 2 cells (iAT2s) have been developed and extensively characterized. Using these cells, Ryan Hekman and colleagues from Boston performed a quantitative phosphoproteomic survey, demonstrating diverse host responses to infection of alveolar epithelial cells and suggesting a dynamic disease signature that evolves as the virus disrupts host programs and rewires modules. Time course analysis revealed rapid remodeling of diverse host systems, including signaling, RNA processing, translation, metabolism, nuclear integrity, protein trafficking, and cytoskeletal-microtubule organization, leading to cell cycle arrest, genotoxic stress, and innate immunity.
Karlsson AC, Humbert M, Buggert M. The known unknowns of T cell immunity to COVID-19. Science Immunology 18 Nov 2020: Vol. 5, Issue 53, eabe8063. Full-text: https://doi.org/10.1126/sciimmunol.abe8063
In their brilliant perspective, Annika C. Karlsson and colleagues from Stockholm, Sweden summarize and speculate on a specific set of questions related to T cell immunity against respiratory viral infections, with a focus on COVID-19 severity, immunity, long-term consequences, and vaccination.
Cervia C, Nilsson J, Zurbuchen Y, et al. Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19. J Allergy Clin Immunol. 2020 Nov 19:S0091-6749(20)31623-7. Full-text: https://doi.org/10.1016/j.jaci.2020.10.040
Using immunoassays specific for SARS-CoV-2 spike proteins, Carlo Cervia and colleagues from Zurich, Switzerland determined SARS-CoV-2-specific IgA and IgG in sera and mucosal fluids of PCR positive patients and of negative HCWs. Serum IgA titers in mild COVID-19 cases were often transiently positive, whereas serum IgG titers remained negative or became positive 12-14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers after symptom onset. Interestingly, some HCWs with negative SARS-CoV-2-specific serum antibody titers showed SARS-CoV-2-specific IgA in mucosal fluids with virus-neutralizing capacity in some cases.
Vaccines
Lederer K, Castaño D, Atria DG, et al. SARS-CoV-2 mRNA vaccines foster potent antigen-specific germinal center responses associated with neutralizing antibody generation. Cell November 21, 2020. Full-text: https://doi.org/10.1016/j.immuni.2020.11.009
A systematic comparison between two vaccine platforms, nucleoside modified mRNA lipid nanoparticle and recombinant protein formulated with the MF59-like adjuvant AddaVax (rRBD-AddaVax), evaluating quantitatively and qualitatively the germinal center (GC) responses to SARS-CoV-2 upon immunization. The authors found that SARS-CoV-2 mRNA vaccines had a superior capacity, in comparison to rRBD-AddaVax, to elicit potent SARS-CoV-2 specific GC B cell responses after the administration of a single vaccine dose. Importantly, they demonstrated that GC B cells and Tfh cells strongly correlated with the production of nAbs.
Clinical
Manzano GS, Woods, JK, Amato AA. Covid-19–Associated Myopathy Caused by Type I Interferonopathy. NEJM November 20, 2020. Full-text: https://doi.org/10.1056/NEJMc2031085
Myalgias and elevated creatine kinase levels are seen in many patients. Whether the elevation in creatine kinase level is caused by viral infection of muscle, toxic effects of cytokines, or another mechanism is unclear. Giovanna S. Manzano and colleagues from Boston describe a COVID-19 patient with myopathy who had a muscle-biopsy specimen showing evidence of virus-induced type I interferonopathy.
Treatment
Bozzi G, Mangioni D, Minoia F, et al. Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: an observational cohort study. J Allergy Clin Immunol. 2020 Nov 18:S0091-6749(20)31621-3. PubMed: https://pubmed.gov/33220354. Full-text: https://doi.org/10.1016/j.jaci.2020.11.006
IL-1 receptor antagonist anakinra is one of the cytokine-blocking agents employed for COVID-19 treatment. Of 120 patients with hyperinflammation (33% on mechanical ventilation), 65 were treated with anakinra and methylprednisolone and 55 were untreated historical controls. At 28 days, mortality was 14% in treated patients and 36% in controls (p = 0,005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared to controls (HR 0,33, p = 0.007 and HR 0,18, p = 0,001, respectively). Randomized, controlled trials including use of either agent alone are needed to confirm these results.
Milewska A, Chi Y, Szczepanski A, et al. HTCC as a Polymeric Inhibitor of SARS-CoV-2 and MERS-CoV. J Virology November 20, 2020. Full-text: https://doi.org/10.1128/JVI.01622-20
The cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) is a potent inhibitor of all known human coronaviruses. Using in vitro and ex vivo models of human airway epithelium, the authors show that HTCC effectively blocks MERS-CoV and SARS-CoV-2 infection.
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