Merge branch 'ms-stats' of https://github.com/greenelab/covid19-review …

…into ms-stats

build/assets/custom-dictionary.txt

@@ -18,11 +18,13 @@ ASBT
 AST
 ATPase
 AUC
+AY
 AZD
 AbbVie
 AbCellera
 Académie
 Acelity
+Acibadem
 Actemra
 Adhanom
 AdVac
@@ -40,6 +42,7 @@ Ashwin
 Assaf
 AstraZeneca
 Avigan
+Aydinlar
 BAL
 BALB
 BALF
@@ -104,6 +107,7 @@ CMV
 CN
 COPD
 COVAX
+COVI
 COVID
 CP
 CPE
@@ -154,6 +158,7 @@ CoVZC
 CoVZXC
 CoVs
 CoV’s
+Codagenix
 Colonic
 Colson
 Comput
@@ -350,12 +355,14 @@ IRF
 IRQ
 ISG
 ISGs
+ITIH
 ITP
 IU
 IgA
 IgG
 IgM
 Immunofluorescence
+Immunologicals
 Ipsita
 JAK
 JJF
@@ -397,6 +404,7 @@ LW
 LY
 LYM
 LYN
+Labmed
 Lactobacillus
 Lafaille
 Lamonica
@@ -433,6 +441,7 @@ MHRA
 MHV
 MIP
 MIS
+MMOA
 MRC
 MUC
 MVN
@@ -454,7 +463,9 @@ Marseille
 MatPlotLib
 Matsuyama
 Meara
+Mehmet
 Mehra
+Meissa
 Melo
 MenACWY
 Meplazumab
@@ -614,6 +625,7 @@ SEB
 SEIR
 SEPPA
 SEYAR
+SIGMAR
 SL
 SMQ
 SNG
@@ -735,6 +747,7 @@ Wildtype
 Willebrand
 Wyler
 Xu
+YF
 YHLO
 Yael
 Yanjun
@@ -759,6 +772,7 @@ aadattoli
 acceptor
 acetylcysteine
 acknowledgements
+actin
 adamlmaclean
 adaptor
 adeno
@@ -850,6 +864,7 @@ bronchioles
 bronchoalveolar
 bronchodilators
 brushings
+bvgh
 byrdjb
 cDNA
 cTnI
@@ -940,6 +955,7 @@ defensins
 deltacoronaviruses
 deltoid
 demethylases
+deoptimized
 der
 detectible
 dexamethasone
@@ -986,6 +1002,7 @@ endonuclease
 endonucleolytic
 endophenotypic
 endoplasmic
+endoprotease
 endosomal
 endosomes
 endothelium
@@ -1029,10 +1046,12 @@ fpcx
 frameshifting
 frontline
 ftzx
+fusogenicity
 gRNA
 gRNAs
 galactooligosaccharides
 gastroenterologist
+gelsolin
 gemcitabine
 generalizability
 genomic
@@ -1048,6 +1067,7 @@ ggpx
 ggvd
 ghjzm
 ghs
+ghstsk
 github
 gjqmvq
 glomerular
@@ -1064,10 +1084,13 @@ glycolic
 glycoproteins
 glycosylated
 glycosylation
+granulocyte
+granulocytes
 greensolid
 greenelab
 gregszetoAI
 grs
+gsfg
 hACE
 hSLAM
 helminths
@@ -1141,6 +1164,7 @@ immunoregulatory
 immunosorbent
 immunostimulants
 immunosuppressant
+immunosuppressants
 immunosuppression
 immunosuppressive
 inconclusivity
@@ -1167,8 +1191,10 @@ interspaced
 interventional
 intracellular
 intradermal
+intraindividual
 intramuscularly
 intranasal
+intranasally
 intraperitoneal
 intraperitoneally
 intratracheal
@@ -1306,12 +1332,14 @@ nanowell
 nanowells
 nasogastric
 nasopharyngeal
+nasopharynx
 naïve
 nebulized
 necropsies
 neuraminic
 neuraminidase
 neurodegenerative
+neuroinflammation
 neuropathological
 neutropenia
 neutrophil
@@ -1320,6 +1348,7 @@ ng
 niclosamide
 nidoviruses
 nilswellhausen
+noncleavable
 nonrandomized
 nonsevere
 nosocomial
@@ -1340,6 +1369,7 @@ oncolytic
 opacities
 orchitis
 orcid
+organismal
 organoid
 organoids
 organoselenium
@@ -1360,6 +1390,7 @@ parainfluenza
 parenchyma
 parvoviruses
 passaged
+passaging
 pathogenesis
 pathogenicity
 pathologic
@@ -1373,6 +1404,7 @@ pfu
 phagocytosed
 phagocytosis
 pharmacodynamic
+pharmacologically
 pharmacovigilance
 phenotypes
 phenotypic
@@ -1527,6 +1559,7 @@ segmental
 selectin
 selenosulfide
 seminiferous
+sequelae
 sera
 seroconversion
 seroconverted
@@ -1607,6 +1640,7 @@ transcriptase
 transcriptional
 transcriptionally
 transcriptome
+transcriptomes
 transcriptomic
 transcriptomics
 transduction
@@ -1621,12 +1655,15 @@ trimer
 trimeric
 trimerization
 troponin
+trypsin
 turbinate
 ubiquitination
 umifenovir
 unadjusted
+uncleaved
 uncoating
 underexplored
+underidentified
 underinsured
 underpowered
 underreported
@@ -1641,6 +1678,7 @@ vaccinia
 vascularized
 vasculitis
 vasodilator
+varicella
 variolation
 vincerubinetti
 virally

content/00.front-matter.md

@@ -21,6 +21,9 @@ was automatically generated
 from [{{manubot.ci_source.repo_slug}}@{{manubot.ci_source.commit | truncate(length=7, end='', leeway=0)}}](https://github.com/{{manubot.ci_source.repo_slug}}/tree/{{manubot.ci_source.commit}})
 {% endif -%}
 on {{manubot.date}}.
+{% if manubot.pdf_url_versioned is defined -%}
+It is also available as a [PDF]({{manubot.pdf_url_versioned}}).
+{% endif -%}
 {% if individual is defined -%}
 It represents one section of a larger evolving review on SARS-CoV-2 and COVID-19 available at <https://greenelab.github.io/covid19-review/>
 {% else -%}

content/22.vaccines.md

@@ -123,8 +123,38 @@ These diverse technology platforms include DNA, RNA, virus-like particle, recomb
 
 ### Live-Attenuated Viruses
 
-<!--To Do: Not used this time I think?-->
-Although this is the vaccine development strategy with the longest history... (short paragraph explaining not really in play here)
+Live-attenuated vaccines (LAV), or replication-competent vaccines, use a weakened living version of a disease-causing virus or a version of a virus that is modified to induce an immune response [@doi:10.1038/s41586-020-2798-3]. 
+The virus can be attenuated by passaging it in a foreign host until, as a consequence of selection pressure, the virus loses its efficacy in the original host. 
+Alternatively, selective gene deletion or codon de-optimization can be utilized to attenuate the virus [@doi:10.1038/s41586-020-2798-3]. 
+LAVs are used globally to prevent diseases caused by viruses such as measles, rubella, polio, influenza, varicella zoster, and the yellow fever virus [@doi:10.1016/B978-0-323-35761-6.00002-X].
+It is generally recognized that LAVs induce an immune response similar to natural infection, and they are favored because they induce long-lasting and robust immunity that can protect from disease. 
+This strong protective effect is induced in part by the immune response to the range of viral antigens available from LAV, which tend to be more immunogenic than those from non-replicating vaccines [@url:https://www.hhs.gov/immunization/basics/types/index.html; @doi:10.1016/j.virol.2015.03.032; @doi:10.3389/fimmu.2020.602256]. 
+LAVs are also favored because they tend to be restricted to viral replication in the tissues around the location of inoculation [@doi:10.1128/9781555818951], and some can be administered intranasally [@doi:10.1038/s41586-020-2798-3]. 
+
+The first deliberate attempt to utilize an attenuated viral vaccine dates back to Louis Pasteur in 1885, despite his not knowing that the disease-causing agent he was experimenting with was a virus. 
+Indeed, the next intentional LAVs developed were intended to prevent illness caused by the yellow fever virus in 1935, followed by the first influenza vaccine in 1936 [@doi:10.1128/9781555818951]. 
+Although LAV development strategies have the longest history, this strategy has not been widely utilized against SARS-CoV-2 and COVID-19. 
+There is general concern that LAV strategies may risk causing disease in individuals who are immunocompromised [@doi:10.1016/j.copbio.2007.10.010], which is an even greater concern when dealing with a novel virus and disease. 
+Previously, there have been numerous attempts to develop both SARS-CoV-1 and MERS-CoV LAVs [@doi:10.3389/fimmu.2020.602256], but no vaccines were approved for use in humans.
+While safety in production was a major concern in the past, nowadays manufacturers of LAVs use safe and reliable methods to produce large quantities of vaccines once they have undergone rigorous preclinical studies and clinical trials to evaluate their safety and efficacy.
+
+There are at least five COVID-19 LAV candidates at various stages of vaccine development.
+A single-dose LAV candidate referred to as YF-SO used live-attenuated yellow fever 17D (YF17D) as a vector for a noncleavable prefusion conformation of the SARS-CoV-2 antigen.
+This LAV has been assessed in hamsters, mice, and macaques [@doi:10.1038/s41586-020-3035-9].
+YF-SO induced a robust immune response in all three animal models and prevented SARS-CoV-2 infection in macaques and hamsters [@doi:10.1038/s41586-020-3035-9].
+Other LAVs being investigated for the prophylaxis of COVID-19 include a Bacillus Calmette-Guerin (BCG) vaccine sponsored by institutes in Australia in collaboration with the Bill and Melinda Gates Foundation, which is in phase III clinical testing [@clinicaltrials:NCT04327206]. 
+A second investigation using a BCG vaccine is also ongoing, which is led by Texas A&M University in collaboration with numerous other U.S. institutions [@clinicaltrials:NCT04348370].
+The purpose of the BCG vaccine is to prevent tuberculosis; however, it is known to exert protective non-specific effects against other respiratory tract infections in _in vitro_ and _in vivo_ studies [@doi:10.1016/j.cmi.2019.04.020], hence the interest many have for its potential use against COVID-19 [@doi:10.1038/s41577-020-0337-y].
+
+In April 2020, it was announced that the Indian Immunologicals Ltd. and Griffith University Australia had partnered to develop codon de-optimized LAV [@url:https://news.griffith.edu.au/2020/04/23/griffith-university-researchers-on-the-road-to-covid-19-vaccine]; however, there have been no updates on the findings of their preclinical testing. 
+Another codon de-optimized LAV is being developed by Mehmet Ali Aydinlar University and Acibadem Labmed Health Services A.S., which also has yet to report the findings of its preclinical tests [@url:https://covid-19tracker.milkeninstitute.org].
+Following successful preclinical investigation [@doi:10.1073/pnas.2102775118], an intranasally administered deoptimized SARS-CoV-2 LAV known as COVI-VAC was developed by both New York-based Codagenix and the Serum Institute of India. 
+COVI-VAC entered phase I human trials and dosed its first participants in January 2021 [@clinicaltrials:NCT04619628; @url:https://covid-19tracker.milkeninstitute.org].  
+It is anticipated that the COVI-VAC phase I human trials will be completed by May 2022.
+Similarly,  Meissa Vaccines in Kansas, U.S.A., which also develops vaccines for _Respiratory syncytial virus_ (RSV), began enrollment for phase I human trials on an intranasal live-attenuated chimeric vaccine candidate in March 2021 for which recruitment is ongoing [@clinicaltrials:NCT04798001; @url:https://covid-19tracker.milkeninstitute.org].
+
+Despite the long and trusted history of LAV development, this vaccine strategy does not appear to be favored for vaccine development against COVID-19.
+Modern technologies such as mRNA vaccines and vectored vaccines seem to have been favored due to their expediency and safety versus the time-consuming nature of developing LAVs using a novel virus.  
 
 ### Inactivated Whole-Virus Vaccines
 

content/40.inequality.md

@@ -281,3 +281,18 @@ This review represents the effort of over 50 contributors <!-- TO DO: check with
 However, this text represents a dynamic and evolving document, and we welcome continued contributions from all researchers who have insights into how these topics intersect.
 A multidisciplinary perspective is critical to understanding this evolving crisis, and in this review we seek to use open science tools to coordinate a response among a variety of researchers.
 We intend to publish additional updates as the situation evolves.
+
+<!-- Additional info on inflammation removed from pathogenesis manuscript, can use here if useful
+Inflammation is one of the most visible components of the immune response, as it is responsible for the hallmarks of injury, such as pain, heat, and swelling [@doi:10.18632/oncotarget.23208].
+The inflammatory response has received particular attention for its role in both a healthy response to infection and a pathogenic one.
+In response to injury or to signaling by pattern recognition receptors indicating the detection of a molecular pattern associated with a pathogen or foreign body, the immune system stimulates leukocytes that travel to the site of the threat, where they then produce cytokines [@doi:10.18632/oncotarget.23208].
+Elevated levels of inflammation over the long-term are associated with many chronic health conditions, including type 2 diabetes, dementia and Alzheimer's, and arthritis [@doi:10.1038/s41591-019-0675-0].
+Some notable pro-inflammatory cytokines include the interleukins IL-1&beta; and IL-6 and tumor necrosis factor &alpha; (TNF-&alpha;) [@doi:10.1097/AIA.0b013e318034194e].
+A number of interleukins and interferons play anti-inflammatory roles, and receptors or receptor antagonists for inflammatory cytokines are also important for regulating inflammation [@doi:10.1097/AIA.0b013e318034194e].
+IL-10 is an anti-inflammatory cytokine of particular note because it regulates the expression of TNF-&alpha;, IL-1, and IL-6 [@doi:10.1097/AIA.0b013e318034194e].
+
+Symptoms of a disease can be caused by a pathogen, but they can also be caused by the immune system's reaction to the pathogen.
+Cytokines are a diverse group of small proteins that play an important role in intercellular signaling [@doi:10.1128/MMBR.05015-11].
+They can be both pro- and anti-inflammatory, meaning they can either stimulate or inhibit the production of additional cytokines [@doi:10.1128/MMBR.05015-11; @doi:10.1097/AIA.0b013e318034194e], with anti-inflammatory cytokines playing an immunoregulatory role complementary to the cascading effect of pro-inflammatory cytokines [@doi:10.1128/MMBR.05015-11; @doi:10.1097/AIA.0b013e318034194e].
+When the pro- and anti-inflammatory responses are both commensurate with the threat posed, the immune system drives a shift back to homeostasis [@doi:10.1111/imr.12671].
+-->

content/60.methods.md

@@ -110,7 +110,7 @@ We also used the Gitter chat platform (<https://www.gitter.im>) to promote infor
 #### Utilization and Expansion of Manubot
 
 Applying Manubot's existing capabilities allowed us to confront several challenges common in large-scale collaborations, such as maintaining a record of contributions that allowed us to allocate credit appropriately or to contact the original author if questions arose.
-Additionally, an up-to-date version of the content was available at all times online at <https://greenelab.github.io/covid19-review/>.
+Additionally, an up-to-date version of the content was available at all times online at <https://greenelab.github.io/covid19-review/> or as a pdf at <https://greenelab.github.io/covid19-review/manuscript.pdf>.
 This approach also allowed us to minimize the demand on authors to curate and sync bibliographic resources.
 Manubot provides the functionality to create a bibliography using digital object identifiers (DOIs), website URLs, or other identifiers such as PubMed identifiers and arXiv IDs.
 The author can insert a citation in-line using a format such as {% raw %}`[@doi:10.1371/journal.pcbi.1007128]`{% endraw %}.
@@ -241,7 +241,7 @@ In addition, Manubot now supports citing clinical trial identifiers such as `cli
 
 ### CONCLUSION
 
-The current project was managed through GitHub in the repository greenelab/covid19-review using Manubot [@doi:10.1371/journal.pcbi.1007128] to continuously generate a version of the manuscript online (<https://greenelab.github.io/covid19-review>).
+The current project was managed through GitHub in the repository greenelab/covid19-review using Manubot [@doi:10.1371/journal.pcbi.1007128] to continuously generate a version of the manuscript online (<https://greenelab.github.io/covid19-review> or <https://greenelab.github.io/covid19-review/manuscript.pdf>).
 The Manubot framework facilitated a massive collaborative review on an urgent topic.
 This project demonstrates that Manubot can be applied to projects where not all collaborators have expertise or even experience working with version control pipelines.
 Through the development of cyberinfrastructure both for training novice users to interact with GitHub and simplifying the workflows to allow them to receive many of the benefits of What You See Is What You Get platforms such as Google Docs, we were able to adapt a powerful open publishing tool to harness the domain expertise of a large group of non-technical users and to respond to the flood of COVID-19 publications.
@@ -262,6 +262,7 @@ This pattern suggests that, as anticipated, we primarily recruited researchers f
 The COVID-19 Review Consortium provided a platform for researchers to engage in scientific investigation during the initial phase of the COVID-19 pandemic in 2020 at a time when many biological scientists were unable to access their research spaces.
 In turn, by seeking to adapt Manubot to allow for broader participation in open publishing from fields where computational training in tools like version control is uncommon, we made a number of improvements that are expected to increase its appeal to researchers from all backgrounds.
 Manubot provided a way for all contributors, including early-career researchers, to join a massive collaborative project, demonstrating their individual contributions to the larger work and gaining experience with version control.
+The licensing and infrastructure also provide an opportunity for individuals to adapt from this project to create their own snapshots of the COVID-19 literature that derive from, but are not wholly identical to, the primary versions of these reviews.
 This project shows that massive online open publishing efforts can indeed advance scholarship through inclusion [@doi:10.5334/kula.63], including during the extreme challenges presented by the COVID-19 pandemic.
 
 ![

content/90.back-matter.md

@@ -10,5 +10,5 @@
 
 <!-- Individual sections that have been published as preprints or journal manuscripts -->
 [@individual-pathogenesis]: arxiv:2102.01521
-[@individual-nutraceuticals]: doi:10.1128/mSystems.00122-21
+[@individual-nutraceuticals]: https://pubmed.ncbi.nlm.nih.gov/33947804/
 [@individual-pharmaceuticals]: arxiv:2103.02723