Copy-editor: Rob Camp
Epidemiology
Siegenfeld AF, Bar-Yam Y. The impact of travel and timing in eliminating COVID-19. Commun Phys 3, 204 (2020). Full-text: https://doi.org/10.1038/s42005-020-00470-7
Mathematical models, showing that these are no good times for travel. When a reduction in travel is coupled with other control measures, the travel reduction will not only delay the spread of the outbreak but in some cases will also be the determining factor in whether or not the outbreak is eliminated.
Kanu FA, Smith EE, Offutt-Powell T, et al. Declines in SARS-CoV-2 Transmission, Hospitalizations, and Mortality After Implementation of Mitigation Measures— Delaware, March–June 2020. MMWR Morb Mortal Wkly Rep. ePub: 6 November 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6945
No single mitigation strategy is likely to be effective alone: State-mandated stay-at-home orders and public mask mandates coupled with case investigations and contact tracing contributed to an 82% reduction in COVID-19 incidence, 88% reduction in hospitalizations, and 100% reduction in mortality in Delaware during late April–June.
Virology
Zheng J, Wong LR, Li K et al. COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice. Nature (2020). Full-text: https://doi.org/10.1038/s41586-020-2943-z
SARS-CoV-2-infected K18-hACE2 mice developed dose-dependent lung disease with features similar to severe human COVID-19, including diffuse alveolar damage, inflammatory cell infiltration, tissue injury, lung vascular damage, and death. Remarkably, K18-hACE2 mice also support SARS-CoV-2 replication in the sinonasal epithelium and associated with this pathology develop anosmia, a common feature of human disease.
Immunology
Chakraborty S, Gonzalez J, Edwards K et al. Proinflammatory IgG Fc structures in patients with severe COVID-19. Nat Immunol 2020, November 9. Full-text: https://doi.org/10.1038/s41590-020-00828-7
Another (important) piece in the puzzle: Saborni Chakraborty and colleagues from Stanford show that specific proinflammatory antibody forms are elevated in more patients with severe COVID-19, in contrast to those with mild symptoms and seropositive children. The unique serologic signature is characterized by IgG3 and IgG1 with F0N0 glycoform modification and includes an increased likelihood of IgG1 with afucosylated Fc glycans. This Fc modification on SARS-CoV-2 IgGs enhanced interactions with the activating Fcγ receptor FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including interleukin-6 and tumor necrosis factor. This may explain why some patients develop severe COVID-19.
Figure 1. SARS-CoV-2 antibodies in patients with COVID-19 and in undiagnosed children. a, Anti-RBD IgM, IgA and IgG titers in patients with COVID-19 who required treatment in the ICU (red; n = 21), hospitalization but no ICU (floor; yellow; n = 22) or treatment on an outpatient basis (light blue; n = 18), and seropositive children (peds; dark blue; n = 16). OD, optical density. b, Anti-RBD AUC for the four patient… | Continue reading at https://doi.org/10.1038/s41590-020-00828-7. Reproduced with permission.
Ng KW, Faulkner N, Cornish GH, et al. Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science 06 Nov 2020. Full-text: https://doi.org/10.1126/science.abe1107
Using multiple independent assays (including flow cytometry-based assay for SARS-CoV-2-binding antibodies), the authors demonstrated the presence of preexisting antibodies recognizing SARS-CoV-2 in at least some uninfected individuals. SARS-CoV-2 spike glycoprotein (S)-reactive antibodies were particularly prevalent in children and adolescents. They were predominantly of the IgG class and targeted the S2 subunit. By contrast, SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S-reactive IgG antibodies, targeting both the S1 and S2 subunits, and concomitant IgM and IgA antibodies, lasting throughout the observation period.
Angioni, R., Sánchez-Rodríguez, R., Munari, F. et al. Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients. Cell Death Dis 11, 957 (2020). Full-text: https://doi.org/10.1038/s41419-020-03151-z
Roberta Angioni and colleagues analyzed the cytokine and leukocyte profile of COVID-19 patients at hospital admission and identified distinctive immunological signatures that characterize younger or older severe patients. They found that severe patients under the age of 60 did not show major leukocyte alterations and expressed high levels of IL-1RA, IL-6, CCL2, CXCL1, CXCL9, CXCL10, and EGF. In contrast, older patients expressed high levels of CXCL8, IL-10, IL-15, IL-27, and TNF-α, presented a significant reduction in the total T lymphocyte number and an increased expression of T cell exhaustion markers as compared to the younger.
Clinical
Avanzato VA, Matson MJ, Seifert SN, et al. Case Study: Prolonged infectious SARS-CoV-2 shedding from an asymptomatic immunocompromised cancer patient. Cell November 04, 2020. Full-text: https://doi.org/10.1016/j.cell.2020.10.049
Immunocompromised patients may shed infectious virus for longer durations than previously recognized: Victoria Avanzato and colleagues describe an interesting case of a female immunocompromised patient with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Shedding of infectious SARS-CoV-2 was observed up to 70 days.
Collateral damage
Jahrami H, BaHammam AS, Bragazzi NL, Saif Z, Faris M, Vitiello MV. Sleep problems during COVID-19 pandemic by population: a systematic review and meta-analysis. J Clin Sleep Med. 2020 Oct 27. PubMed: https://pubmed.gov/33108269. Full-text: https://doi.org/10.5664/jcsm.8930
Forty-four papers, involving a total of 54,231 participants from 13 countries, contributed to this systematic review and meta-analysis of sleep problems during COVID-19. The global pooled prevalence rate of sleep problems among all populations was 35.7%. COVID-19 patients appeared to be the most affected group, with a pooled rate of 74.8%. Healthcare workers and the general population had comparative rates of sleep problems with rates of 36.0% and 32.3%, respectively.
Dyer O. Covid-19: Denmark to kill 17 million minks over mutation that could undermine vaccine effort. BMJ 2020; 371:m4338. Full-text: https://doi.org/10.1136/bmj.m4338
Among 5,102 samples of virus taken from Danish patients since June, five infection clusters affecting 214 people involved mink variant virus. One of these, known as cluster 5, seems to be a problematic variant which could be less susceptible to some antibodies/vaccines (unproven). This variant has been detected with four simultaneous changes in the genes for the Spike protein (for nerds: H69del/V70del, Y453F, I692V and M1229I) and has affected 11 people in North Jutland. Conclusion: 17 million minks will be culled.
Severe COVID
Liu Y, Lv J, Liu J. et al. Mucus production stimulated by IFN-AhR signaling triggers hypoxia of COVID-19. Cell Res November 6, 2020. Full-text: https://doi.org/10.1038/s41422-020-00435-z
It’s mucus: this great work may potentially explain the silent hypoxia that has emerged as a unique feature of COVID-19. Yuying Liu and colleagues from Beijing/China show that mucins are accumulated in the bronchoalveolar lavage fluid and are upregulated in the lungs of severe SARS-CoV-2-infected mice and macaques. They also found that induction of either interferon (IFN)-β or IFN-γ upon SARS-CoV-2 infection results in activation of aryl hydrocarbon receptor (AhR) signaling through an IDO-Kyn-dependent pathway, leading to transcriptional upregulation of the expression of mucins, both the secreted and membrane-bound, in alveolar epithelial cells. Consequently, accumulated alveolar mucus affects the blood-gas barrier, thus inducing hypoxia and diminishing lung capacity, which can be reversed by blocking AhR activity.
Figure 7. A schematic for AhR-upregulated mucins in the hypoxia of COVID-19 patients. A normal gas exchange between the alveoli and pulmonary capillary blood is achieved through a passive diffusion of O2 and CO2. During SARS-CoV-2 infection, increased IFN-β and IFN-γ… | Continue reading at https://doi.org/10.1038/s41422-020-00435-z. Reproduced with permission.