Top 10: November 17

Copy-editor: Rob Camp

Epidemiology

Mahale P, Rothfuss C, Bly S, et al. Multiple COVID-19 Outbreaks Linked to a Wedding Reception in Rural Maine — August 7–September 14, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1686–1690. Full-text: http://dx.doi.org/10.15585/mmwr.mm6945a5

Do you have a niece who, despite all the warnings, is unwaveringly sticking to her plans to get married in January? Who says that only 50 guests (ok, 55) will come and that temperature checks for all guests will be conducted at the facility entrance? That there will be enough space, with 10 tables, with 4–6 guests seated around each table? That signs posted at the entrance will instruct visitors to wear masks? Then give her this paper to read. A wedding reception in a small rural town in Maine was the likely source of COVID-19 outbreaks in the local community, a long-term care facility, and a correctional facility. Outcome: 177 cases, seven hospitalizations, and seven deaths. Read here why people should avoid large gatherings, practice physical distancing, wear masks, stay home when ill, and self-quarantine after exposure to a person with confirmed SARS-CoV-2 infection.

(If your niece doesn’t want to read a scientific paper, provide her with “15 Benefits of A Summer Wedding”: https://www.nichemarket.co.za/blog/extravaganza/benefits-summer-wedding. Benefit No. 16 is found probably below, in the vaccine section.)

Graphical abstract:

 

 

Ali H, Kondapally K, Pordell P, et al. COVID-19 Outbreak in an Amish Community — Ohio, May 2020. MMWR Morb Mortal Wkly Rep 2020;69:1671–1674. Full-text:  http://dx.doi.org/10.15585/mmwr.mm6945a2

How social gatherings likely contributed to rapid transmission of SARS-CoV-2 in an Amish community. In May, after a cluster of seven COVID-19 cases was identified, 23/30 (77%) additional residents tested by RT-PCR received positive test results. Rapid and sustained transmission of SARS-CoV-2 was associated with multiple social gatherings. Although Amish communities might be experiencing challenges with preventing and mitigating SARS-CoV-2 transmission, the authors conclude that leveraging Amish cultural beliefs of communal responsibility could help limit the spread of SARS-CoV-2.

 

Wang EA, Western B, Berwick DM. COVID-19, Decarceration, and the Role of Clinicians, Health Systems, and Payers. A Report From the National Academy of Sciences, Engineering, and Medicine. JAMA November 16, 2020. Full-text: https://doi.org/10.1001/jama.2020.22109

By August 2020, 90 of the largest 100 cluster outbreaks in the United States had occurred in prisons and jails. Reducing the incarcerated population (“decarceration”) is an important and urgent strategy for mitigating viral transmission in prisons and jails. In their courageous viewpoint, Emily Wang and colleagues argue that decarceration in the service of both public health and safer communities will require sustained engagement from clinicians, health systems, and Medicaid authorities.

 

Immunology

Knierman MD, Lannan MB, Spindler LJ, et al. The Human Leukocyte Antigen Class II Immunopeptidome of SARS-CoV-2 Spike Glycoprotein. Cell Rep November 13, 2020. Full-text: https://doi.org/10.1016/j.celrep.2020.108454

Using mass spectrometry, Michael D Knierman and colleagues from Lilly performed a precise and comprehensive immunopeptidomic investigation with SARS-CoV-2 spike glycoprotein. They identified 526 unique sequences from SARS-CoV-2 spike glycoprotein extracellular domain in a complex with HLA class II molecules on antigen presenting cells from a panel of healthy donors. The identified sequences spanned the entire spike protein and several sequences were isolated from a majority of the donors sampled, indicating promiscuous binding. This is good news, as both the depth and breadth of the HLA-II peptides indicate that mutational drift is not expected to dramatically alter the ability of an infected individual to mount a new B cell response.

 

Vaccine

Callaway E. COVID vaccine excitement builds as Moderna reports third positive result. Nature NEWS November 16, 2020. Full-text: https://doi.org/10.1038/d41586-020-03248-7

Moderna’s vaccine comprises RNA instructions for cells to produce a modified form of the coronavirus spike protein, the immune system’s key target against coronaviruses. Of note, the vaccine remains stable in conventional refrigerators for a month and ordinary freezers for six months. Ewen Callaway summarizes preliminary data showing that the immunization is 94% effective and seems to prevent severe infections.

 

Diagnostics

Gniffke EP, Harrington WE, Dambrauskas N, et al. Plasma From Recovered COVID-19 Patients Inhibits Spike Protein Binding to ACE2 in a Microsphere-Based Inhibition Assay. J Infect Dis. 2020 Nov 13;222(12):1965-1973. PubMed: https://pubmed.gov/32798222 . Full-text: https://doi.org/10.1093/infdis/jiaa508

A new microsphere-based flow cytometry assay that quantifies the ability of plasma to inhibit the binding of spike protein to ACE2. Plasma from 22 patients who had recovered from mild COVID-19 and expressed anti–spike protein trimer immunoglobulin G (IgG) inhibited ACE2–spike protein binding to a greater degree than controls. The degree of inhibition was correlated with anti–spike protein IgG levels, neutralizing titers in a pseudotyped lentiviral assay, and the presence of fever during illness. This inhibition assay may be broadly useful to quantify the functional antibody response of patients recovered from COVID-19 or vaccine recipients in a cell-free assay system.

 

Clinical

Coate KC, Cha , Shrestha S. SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 are Expressed in the Microvasculature and Ducts of Human Pancreas but are Not Enriched in β Cells. Cell Metabolism November 13, 2020. Full-text: https://doi.org/10.1016/j.cmet.2020.11.006

Isolated reports of new-onset diabetes in COVID-19 cases have led to the hypothesis that SARS-CoV-2 is directly cytotoxic to pancreatic islet β cells. Katie Coate and colleagues show here that it’s not that easy. In pancreatic sections, ACE2 and TMPRSS2 protein (the main cell entry factors) were not detected in β cells from donors with and without diabetes. Instead, ACE2 protein was expressed in islet and exocrine tissue microvasculature and in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. Contrasting with previous reports, this careful investigation suggests that the interaction of diabetes and SARS-CoV-2 is mediated by systemic inflammation and/or metabolic changes in other organs such as liver, muscle or adipose tissue (and not by a direct infection of β cells in the pancreas).

 

Shi Z, de Vries HJ, Vlaar AP, et al. Diaphragm Pathology in Critically Ill Patients With COVID-19 and Postmortem Findings From 3 Medical Centers. JAMA Intern Med November 16, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.6278

This study focused on the diaphragm, the main muscle of respiration. Consecutive diaphragm muscle specimens from 26 deceased COVID-19 patients were compared with autopsy diaphragm specimens of 8 patients who had been critically ill without COVID-19. There was an increased expression of genes involved in fibrosis and histological evidence for the development of fibrosis in the diaphragm. Of note, this myopathic phenotype was distinctly different from that of control ICU patients, with comparable duration of mechanical ventilation and ICU length of stay. It is hypothesized that severe myopathy may lead to diaphragm weakness and might contribute to ventilator weaning failure, persistent dyspnea, and fatigue in COVID-19 survivors.

 

Miller DG, Piesron L, Doernberg S. The Role of Medical Students During the COVID-19 Pandemic. Annals Int Med 2020, November 17. Full-text: https://doi.org/10.7326/L20-1195

Interesting discussion about in-person medical student involvement during the COVID-19 pandemic. Some authors argue for it, others against it. Both sides have good arguments.

 

Collateral Damage

Leske S, Kõlves K, Cromton D, et al. Real-time suicide mortality data from police reports in Queensland, Australia, during the COVID-19 pandemic: an interrupted time-series analysis. Lancet Psychiatry, November 16, 2020. Full-text: https://doi.org/10.1016/S2215-0366(20)30435-1

Do suicide rates increase during infectious disease outbreaks? Probably not (at least in Australia). In this study, analyzing suspected suicide rates in 2020 relative to 2015–19 to assess any early effects of the COVID-19 pandemic in Queensland, no evidence of a change in suspected suicide rates was seen.

 

 


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