Difference between revisions of "Journal:Comprehensive analyses of SARS-CoV-2 transmission in a public health virology laboratory"

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[[SARS-CoV-2]] has become a major global concern as of December 2019, particularly affecting healthcare workers. As person-to-person transmission is airborne, crowded closed spaces have had high potential for rapid virus spread, especially early in the [[pandemic]] when social distancing and mask wearing were not mandatory. This retrospective study thoroughly investigates a small-scale SARS-CoV-2 outbreak in Israel’s central virology laboratory (ICVL) in mid-March 2020, in which six staff members and two related family members were infected. Suspicions regarding infection by contaminated surfaces in ICVL facilities were nullified by the negative results of a SARS-CoV-2 [[Polymerase chain reaction#Variations|real-time polymerase chain reaction]] (qPCR) analysis of swiped work surface samples. Complete SARS-CoV-2 [[Genomics|genomes]] were [[Sequencing|sequenced]], and mutation analyses showed inclusion of all samples to [[Wikipedia:Clade|clades]] 20B and 20C, possessing the spike mutation D614G. Phylogenetic analysis clarified transmission events, confirming S1 as having infected at least three other staff members while refuting the association of a staff member’s infected spouse with the ICVL transmission cluster. Finally, serology tests exhibited IgG and IgA antibodies in all infected individuals and revealed the occurrence of asymptomatic infections in additional staff members. This study demonstrates the advantages of molecular [[epidemiology]] in elucidating transmission events and exemplifies the importance of good [[laboratory]] practice, physical distancing, and mask wearing in preventing SARS-CoV-2 spread, specifically in healthcare facilities.
[[SARS-CoV-2]] has become a major global concern as of December 2019, particularly affecting healthcare workers. As person-to-person transmission is airborne, crowded closed spaces have had high potential for rapid virus spread, especially early in the [[pandemic]] when social distancing and mask wearing were not mandatory. This retrospective study thoroughly investigates a small-scale SARS-CoV-2 outbreak in Israel’s central virology laboratory (ICVL) in mid-March 2020, in which six staff members and two related family members were infected. Suspicions regarding infection by contaminated surfaces in ICVL facilities were nullified by the negative results of a SARS-CoV-2 [[Polymerase chain reaction#Variations|real-time polymerase chain reaction]] (qPCR) analysis of swiped work surface samples. Complete SARS-CoV-2 [[Genomics|genomes]] were [[Sequencing|sequenced]], and mutation analyses showed inclusion of all samples to [[Wikipedia:Clade|clades]] 20B and 20C, possessing the spike mutation D614G. Phylogenetic analysis clarified transmission events, confirming S1 as having infected at least three other staff members while refuting the association of a staff member’s infected spouse with the ICVL transmission cluster. Finally, serology tests exhibited IgG and IgA antibodies in all infected individuals and revealed the occurrence of asymptomatic infections in additional staff members. This study demonstrates the advantages of molecular [[epidemiology]] in elucidating transmission events and exemplifies the importance of good [[laboratory]] practice, physical distancing, and mask wearing in preventing SARS-CoV-2 spread, specifically in healthcare facilities.


'''Keywords''': 2019-nCoV, SARS-CoV-2, COVID-19, staff, infection, next generation sequencing (NGS)
'''Keywords''': 2019-nCoV, SARS-CoV-2, COVID-19, staff, infection, next-generation sequencing (NGS)


==Introduction==
==Introduction==
[[SARS-CoV-2]] (severe acute respiratory syndrome coronavirus 2) is a novel [[coronavirus]] that emerged in Wuhan, China in December 2019<ref name="LuOut20">{{cite journal |title=Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle |journal=Journal of Medical Virology |author=Lu, H.; Stratton, C.W.; Tang, Y.-W. |volume=92 |issue=4 |pages=401–2 |year=2020 |doi=10.1002/jmv.25678 |pmid=31950516 |pmc=PMC7166628}}</ref> and has rapidly spread across China and to many countries worldwide, causing severe respiratory disease leading to substantial morbidity and mortality.<ref name="LiEarly20">{{cite journal |title=Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia |journal=The New England Journal of Medicine |author=Li, Q.; Guan, X.; Wu, P. et al. |year=2020 |doi=10.1056/NEJMoa2001316 |pmid=31995857}}</ref><ref name="WangANovel20">{{cite journal |title=A novel coronavirus outbreak of global health concern |journal=Lancet |author=Wang, C.; Horby, P.W.; Hayden, F.G. et al. |volume=395 |issue=10223 |pages=470–73 |year=2020 |doi=10.1016/S0140-6736(20)30185-9 |pmid=31986257 |pmc=PMC7135038}}</ref><ref name="HolshueFirst20">{{cite journal |title=First Case of 2019 Novel Coronavirus in the United States |journal=New England Journal of Medicine |author=Holshue, M.L.; DeBolt, C.; Lindquist, S. et al. |volume=382 |issue=10 |pages=929–36 |year=2020 |doi=10.1056/NEJMoa2001191 |pmid=32004427 |pmc=PMC7092802}}</ref><ref name="BajemaPersons20">{{cite journal |title=Persons Evaluated for 2019 Novel Coronavirus - United States, January 2020 |journal=Morbidity and Mortality Weekly Report |author=Bajema, K.L.; Oster, A.M.; McGovern, O.L. et al. |volume=69 |issue=6 |pages=166–70 |year=2020 |doi=10.15585/mmwr.mm6906e1 |pmid=32053579 |pmc=PMC7017962}}</ref><ref name="CDCCOVIDView">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html |title=COVIDView: A Weekly Surveillance Summary of U.S. COVID-19 Activity |author=Centers for Disease Control and Prevention |publisher=Centers for Disease Control and Prevention |accessdate=03 July 2020}}</ref> This novel virus is a potential threat to human health worldwide and a major global health concern due to person-to-person transmission, a current lack of vaccination, and a lack of effective therapeutic options.<ref name="WangANovel20" /><ref name="WHOCorona">{{cite web |url=https://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/novel-coronavirus-2019-ncov |title=Coronavirus disease (COVID-19) pandemic |author=World Health Organization |publisher=World Health Organization |accessdate=15 July 2020}}</ref> Major SARS-CoV-2 worldwide [[Wikipedia:Clade|clades]] have been proposed by nomenclature systems, including Nextstrain<ref name="HadfieldNextstrain18">{{cite journal |title=Nextstrain: Real-time tracking of pathogen evolution |journal=Bioinformatics |author=Hadfield, J.; Megill, C.; Bell, S.M. et al. |volume=34 |issue=23 |pages=4121-4123 |year=2018 |doi=10.1093/bioinformatics/bty407 |pmid=29790939 |pmc=PMC6247931}}</ref> and the Global Initiative on Sharing All Influenza Data (GISAID).<ref name="ElbeData17">{{cite journal |title=Data, disease and diplomacy: GISAID's innovative contribution to global health |journal=Global Challenges |author=Elbe, S.; Buckland-Merrett, G. |volume=1 |issue=1 |pages=33–46 |year=2017 |doi=10.1002/gch2.1018 |pmid=31565258 |pmc=PMC6607375}}</ref> These are based on viral genomes from >57,000 sequences submitted in GISAID.<ref name="ElbeData17" /> For example, using Nextstrain’s nomenclature, there are currently five major clades: 19A (the root clade) and 19B, and clades 20A, B, and C. These are widespread in Europe and include a mutation in the spike protein, D614G, that is associated with increased infectivity and higher viral loads.<ref name="KorberTracking20">{{cite journal |title=Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus |journal=Cell |author=Korber, B.; Fischer, W.M.; Gnanakaran, S. et al. |volume=S0092-8674 |issue=20 |pages=30820-5 |year=2020 |doi=10.1016/j.cell.2020.06.043 |pmid=32697968 |pmc=PMC7332439}}</ref>
[[SARS-CoV-2]] (severe acute respiratory syndrome coronavirus 2) is a novel [[coronavirus]] that emerged in Wuhan, China in December 2019<ref name="LuOut20">{{cite journal |title=Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle |journal=Journal of Medical Virology |author=Lu, H.; Stratton, C.W.; Tang, Y.-W. |volume=92 |issue=4 |pages=401–2 |year=2020 |doi=10.1002/jmv.25678 |pmid=31950516 |pmc=PMC7166628}}</ref> and has rapidly spread across China and to many countries worldwide, causing severe respiratory disease leading to substantial morbidity and mortality.<ref name="LiEarly20">{{cite journal |title=Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia |journal=The New England Journal of Medicine |author=Li, Q.; Guan, X.; Wu, P. et al. |year=2020 |doi=10.1056/NEJMoa2001316 |pmid=31995857}}</ref><ref name="WangANovel20">{{cite journal |title=A novel coronavirus outbreak of global health concern |journal=Lancet |author=Wang, C.; Horby, P.W.; Hayden, F.G. et al. |volume=395 |issue=10223 |pages=470–73 |year=2020 |doi=10.1016/S0140-6736(20)30185-9 |pmid=31986257 |pmc=PMC7135038}}</ref><ref name="HolshueFirst20">{{cite journal |title=First Case of 2019 Novel Coronavirus in the United States |journal=New England Journal of Medicine |author=Holshue, M.L.; DeBolt, C.; Lindquist, S. et al. |volume=382 |issue=10 |pages=929–36 |year=2020 |doi=10.1056/NEJMoa2001191 |pmid=32004427 |pmc=PMC7092802}}</ref><ref name="BajemaPersons20">{{cite journal |title=Persons Evaluated for 2019 Novel Coronavirus - United States, January 2020 |journal=Morbidity and Mortality Weekly Report |author=Bajema, K.L.; Oster, A.M.; McGovern, O.L. et al. |volume=69 |issue=6 |pages=166–70 |year=2020 |doi=10.15585/mmwr.mm6906e1 |pmid=32053579 |pmc=PMC7017962}}</ref><ref name="CDCCOVIDView">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html |title=COVIDView: A Weekly Surveillance Summary of U.S. COVID-19 Activity |author=Centers for Disease Control and Prevention |publisher=Centers for Disease Control and Prevention |accessdate=03 July 2020}}</ref> This novel virus is a potential threat to human health worldwide and a major global health concern due to person-to-person transmission, a current lack of vaccination, and a lack of effective therapeutic options.<ref name="WangANovel20" /><ref name="WHOCorona">{{cite web |url=https://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/novel-coronavirus-2019-ncov |title=Coronavirus disease (COVID-19) pandemic |author=World Health Organization |publisher=World Health Organization |accessdate=15 July 2020}}</ref> Major SARS-CoV-2 worldwide [[Wikipedia:Clade|clades]] have been proposed by nomenclature systems, including Nextstrain<ref name="HadfieldNextstrain18">{{cite journal |title=Nextstrain: Real-time tracking of pathogen evolution |journal=Bioinformatics |author=Hadfield, J.; Megill, C.; Bell, S.M. et al. |volume=34 |issue=23 |pages=4121-4123 |year=2018 |doi=10.1093/bioinformatics/bty407 |pmid=29790939 |pmc=PMC6247931}}</ref> and the Global Initiative on Sharing All Influenza Data (GISAID).<ref name="ElbeData17">{{cite journal |title=Data, disease and diplomacy: GISAID's innovative contribution to global health |journal=Global Challenges |author=Elbe, S.; Buckland-Merrett, G. |volume=1 |issue=1 |pages=33–46 |year=2017 |doi=10.1002/gch2.1018 |pmid=31565258 |pmc=PMC6607375}}</ref> These are based on viral genomes from >57,000 sequences submitted in GISAID.<ref name="ElbeData17" /> For example, using Nextstrain’s nomenclature, there are currently five major clades: 19A (the root clade) and 19B, and clades 20A, B, and C. These are widespread in Europe and include a mutation in the spike protein, D614G, that is associated with increased infectivity and higher viral loads.<ref name="KorberTracking20">{{cite journal |title=Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus |journal=Cell |author=Korber, B.; Fischer, W.M.; Gnanakaran, S. et al. |volume=S0092-8674 |issue=20 |pages=30820-5 |year=2020 |doi=10.1016/j.cell.2020.06.043 |pmid=32697968 |pmc=PMC7332439}}</ref>


Non-SARS-CoV-2 human coronaviruses have been circulating worldwide since the late 1960s.<ref name="BradburneEffect67">{{cite journal |title=Effects of a "new" human respiratory virus in volunteers |journal=British Medical Journal |author=Bradburne, A.F.; Bynoe, M.L.; Tyrrell, D.A. |volume=3 |issue=5568 |pages=767–9 |year=1967 |doi=10.1136/bmj.3.5568.767 |pmid=6043624 |pmc=PMC1843247}}</ref><ref name="LarsonIsol80">{{cite journal |title=Isolation of rhinoviruses and coronaviruses from 38 colds in adults |journal=Journal of Medical Virology |author=Larson, H.E.; Reed, S.E.; Tyrrell, D.A. |volume=5 |issue=3 |pages=221–9 |year=1980 |doi=10.1002/jmv.1890050306 |pmid=6262450 |pmc=PMC7167084}}</ref> The current rate of circulation of SARS-CoV-2 in Israel in the winter season is still unknown; however, analysis of Israeli specimens during the 2015–2016 winter season revealed that non-SARS-CoV-2 human coronaviruses circulate simultaneously with other common respiratory viruses, with 10% human coronavirus-positive cases.<ref name="FriedmanHuman18">{{cite journal |title=Human Coronavirus Infections in Israel: Epidemiology, Clinical Symptoms and Summer Seasonality of HCoV-HKU1 |journal=Viruses |author=Friedman, N.; Alter, H.; Hindiyeh, M. et al. |volume=10 |issue=10 |at=515 |year=1980 |doi=10.3390/v10100515 |pmid=30241410 |pmc=PMC6213580}}</ref>
SARS-CoV-2 circulation in the general population in Israel and worldwide is being assessed using [[Polymerase chain reaction#Variations|real-time polymerase chain reaction]] (qPCR). A rapid development of qPCR diagnostic tests specific for SARS-CoV-2 genes has enabled fast and accurate laboratory tests for suspected individuals.<ref name="CormanDetect20">{{cite journal |title=Detection of 2019 Novel Coronavirus (2019-nCoV) by Real-Time RT-PCR |journal=Euro Surveillance |author=Corman, V.M.; Landt, O.; Kaiser, M. et al. |volume=25 |issue=3 |at=2000045 |year=2020 |doi=10.2807/1560-7917.ES.2020.25.3.2000045 |pmid=31992387 |pmc=PMC6988269}}</ref> These tests were successfully evaluated in Israel’s central virology laboratory (ICVL), where SARS-CoV-2 suspected specimens were exclusively examined, starting from the first importation case of SARS-CoV-2 into Israel at the end of February until the middle of March 2020. Starting with the first suspected case in Israel, all specimens received in ICVL facilities were dealt with using the strictest safety directions and [[Biosafetly level#Levels|biosafety level 2 (BSL2) or greater safety conditions.<ref name="WHOLab13">{{cite web |url=https://www.who.int/csr/disease/coronavirus_infections/Biosafety_InterimRecommendations_NovelCoronavirus_19Feb13.pdf |format=PDF |title=Laboratory biorisk management for laboratories handling human specimens suspected or confirmed to contain novel coronavirus: Interim recommendations |author=World Health Organization |publisher=World Health Organization |date=19 February 2013 |accessdate=11 May 2020}}</ref><ref name="CDCInterim20">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/lab/lab-biosafety-guidelines.html |title=Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 (COVID-19) |author=Centers for Disease Control and Prevention |publisher=Centers for Disease Control and Prevention |accessdate=11 May 2020}}</ref> Until mid-March 2020, all SARS-CoV-2 positive cases in Israel were isolated in a designated quarantine facility; however, physical distancing and mandatory mask-wearing were not customary or enforced at that time in Israel.
In mid-March 2020, several cases of SARS-CoV-2 infection were identified in ICVL, some of which probably originated from an infected worker, as speculated by the inquiry-based [[Epidemiology|epidemiological]] investigation. SARS-CoV-2 airborne transmission was demonstrated to be the most efficient among all transmission routes<ref name="LoftiCOVID20">{{cite journal |title=COVID-19: Transmission, prevention, and potential therapeutic opportunities |journal=Clinica Chimica Acta |author=Lotfi, M.; Hamblin, M.R.; Rezaei, N. |volume=508 |pages=254–66 |year=2020 |doi=10.1016/j.cca.2020.05.044 |pmid=32474009 |pmc=PMC7256510}}</ref><ref name="LoftiCOVID20">{{cite journal |title=Identifying airborne transmission as the dominant route for the spread of COVID-19 |journal=Proceedings of the National Academy of Sciences of the United States of America |author=Zhang, R.; Li, Y.; Zhang, A.L. et al. |volume=117 |issue=26 |pages=14857-14863 |year=2020 |doi=10.1073/pnas.2009637117 |pmid=32527856 |pmc=PMC7334447}}</ref>, and contagious even in the pre-symptomatic stages<ref name="LaiAsymp20">{{cite journal |title=Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths |journal=Journal of Microbiology, Immunology, and Infection |author=Lai, C.-C.; Liu, Y.H.; Wang, C,-Y. et al. |volume=53 |issue=3 |pages=404–12 |year=2020 |doi=10.1016/j.jmii.2020.02.012 |pmid=32173241 |pmc=PMC7128959}}</ref><ref name="RotheTransm20">{{cite journal |title=Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany |journal=New England Journal of Medicine |author=Rothe, C.; Schunk, M.; Sothmann, P. et al. |volume=382 |issue=10 |pages=970-971 |year=2020 |doi=10.1056/NEJMc2001468 |pmid=32003551 |pmc=PMC7120970}}</ref>, such that silent virus spread easily occurs. Infection at workplaces was shown as a common transmission route in Israel in the early stages of the virus' spread, probably facilitated, in the case of the ICVL outbreak, by crowded workspaces and lack of social distancing and mask wearing at that time.
This study thoroughly investigates the SARS-CoV-2 ICVL outbreak by examining infected ICVL workers, several epidemiologically-related family members, and work surfaces from ICVL facilities. Application of SARS-CoV-2 whole [[Genomics|genome]] [[next-generation sequencing]] (NGS), qPCR, serology testing, and phylogenetic tree analyses elucidate person-to-person transmission events, map individual and common mutations, and examine suspicions regarding contaminated surfaces. This study demonstrates the added value of molecular epidemiology based on complete viral genomes in elucidating person-to-person transmission, reveals silent infections in non-symptomatic ICVL staff members via serology testing, and confirms that the strict safety regulations observed in ICVL most likely prevented further spread of the virus.


==References==
==References==

Revision as of 19:43, 17 August 2020

Full article title Comprehensive analyses of SARS-CoV-2 transmission in a public health virology laboratory
Journal Viruses
Author(s) Zuckerman, Neta S.; Pando, Rakafet; Bucris, Efrat; Drori, Yaron; Lustig, Yaniv; Erster, Oran;
Mor, Orna; Mendelson, Ella; Mandelboim, Michael
Author affiliation(s) Chaim Sheba Medical Center, Israel Ministry of Health, Tel-Aviv University
Primary contact Email: michalman at sheba dot health dot gov dot il
Year published 2020
Volume and issue 12(8)
Article # 854
DOI 10.3390/v12080854
ISSN 1999-4915
Distribution license Creative Commons Attribution 4.0 International
Website https://www.mdpi.com/1999-4915/12/8/854/htm
Download https://www.mdpi.com/1999-4915/12/8/854/pdf (PDF)
Emblem-important-yellow.svg This article should be considered a work in progress and incomplete. Consider this article incomplete until this notice is removed.

Abstract

SARS-CoV-2 has become a major global concern as of December 2019, particularly affecting healthcare workers. As person-to-person transmission is airborne, crowded closed spaces have had high potential for rapid virus spread, especially early in the pandemic when social distancing and mask wearing were not mandatory. This retrospective study thoroughly investigates a small-scale SARS-CoV-2 outbreak in Israel’s central virology laboratory (ICVL) in mid-March 2020, in which six staff members and two related family members were infected. Suspicions regarding infection by contaminated surfaces in ICVL facilities were nullified by the negative results of a SARS-CoV-2 real-time polymerase chain reaction (qPCR) analysis of swiped work surface samples. Complete SARS-CoV-2 genomes were sequenced, and mutation analyses showed inclusion of all samples to clades 20B and 20C, possessing the spike mutation D614G. Phylogenetic analysis clarified transmission events, confirming S1 as having infected at least three other staff members while refuting the association of a staff member’s infected spouse with the ICVL transmission cluster. Finally, serology tests exhibited IgG and IgA antibodies in all infected individuals and revealed the occurrence of asymptomatic infections in additional staff members. This study demonstrates the advantages of molecular epidemiology in elucidating transmission events and exemplifies the importance of good laboratory practice, physical distancing, and mask wearing in preventing SARS-CoV-2 spread, specifically in healthcare facilities.

Keywords: 2019-nCoV, SARS-CoV-2, COVID-19, staff, infection, next-generation sequencing (NGS)

Introduction

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus that emerged in Wuhan, China in December 2019[1] and has rapidly spread across China and to many countries worldwide, causing severe respiratory disease leading to substantial morbidity and mortality.[2][3][4][5][6] This novel virus is a potential threat to human health worldwide and a major global health concern due to person-to-person transmission, a current lack of vaccination, and a lack of effective therapeutic options.[3][7] Major SARS-CoV-2 worldwide clades have been proposed by nomenclature systems, including Nextstrain[8] and the Global Initiative on Sharing All Influenza Data (GISAID).[9] These are based on viral genomes from >57,000 sequences submitted in GISAID.[9] For example, using Nextstrain’s nomenclature, there are currently five major clades: 19A (the root clade) and 19B, and clades 20A, B, and C. These are widespread in Europe and include a mutation in the spike protein, D614G, that is associated with increased infectivity and higher viral loads.[10]

Non-SARS-CoV-2 human coronaviruses have been circulating worldwide since the late 1960s.[11][12] The current rate of circulation of SARS-CoV-2 in Israel in the winter season is still unknown; however, analysis of Israeli specimens during the 2015–2016 winter season revealed that non-SARS-CoV-2 human coronaviruses circulate simultaneously with other common respiratory viruses, with 10% human coronavirus-positive cases.[13]

SARS-CoV-2 circulation in the general population in Israel and worldwide is being assessed using real-time polymerase chain reaction (qPCR). A rapid development of qPCR diagnostic tests specific for SARS-CoV-2 genes has enabled fast and accurate laboratory tests for suspected individuals.[14] These tests were successfully evaluated in Israel’s central virology laboratory (ICVL), where SARS-CoV-2 suspected specimens were exclusively examined, starting from the first importation case of SARS-CoV-2 into Israel at the end of February until the middle of March 2020. Starting with the first suspected case in Israel, all specimens received in ICVL facilities were dealt with using the strictest safety directions and [[Biosafetly level#Levels|biosafety level 2 (BSL2) or greater safety conditions.[15][16] Until mid-March 2020, all SARS-CoV-2 positive cases in Israel were isolated in a designated quarantine facility; however, physical distancing and mandatory mask-wearing were not customary or enforced at that time in Israel.

In mid-March 2020, several cases of SARS-CoV-2 infection were identified in ICVL, some of which probably originated from an infected worker, as speculated by the inquiry-based epidemiological investigation. SARS-CoV-2 airborne transmission was demonstrated to be the most efficient among all transmission routes[17][17], and contagious even in the pre-symptomatic stages[18][19], such that silent virus spread easily occurs. Infection at workplaces was shown as a common transmission route in Israel in the early stages of the virus' spread, probably facilitated, in the case of the ICVL outbreak, by crowded workspaces and lack of social distancing and mask wearing at that time.

This study thoroughly investigates the SARS-CoV-2 ICVL outbreak by examining infected ICVL workers, several epidemiologically-related family members, and work surfaces from ICVL facilities. Application of SARS-CoV-2 whole genome next-generation sequencing (NGS), qPCR, serology testing, and phylogenetic tree analyses elucidate person-to-person transmission events, map individual and common mutations, and examine suspicions regarding contaminated surfaces. This study demonstrates the added value of molecular epidemiology based on complete viral genomes in elucidating person-to-person transmission, reveals silent infections in non-symptomatic ICVL staff members via serology testing, and confirms that the strict safety regulations observed in ICVL most likely prevented further spread of the virus.

References

  1. ↑ Lu, H.; Stratton, C.W.; Tang, Y.-W. (2020). "Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle". Journal of Medical Virology 92 (4): 401–2. doi:10.1002/jmv.25678. PMC PMC7166628. PMID 31950516. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166628. 
  2. ↑ Li, Q.; Guan, X.; Wu, P. et al. (2020). "Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia". The New England Journal of Medicine. doi:10.1056/NEJMoa2001316. PMID 31995857. 
  3. ↑ 3.0 3.1 Wang, C.; Horby, P.W.; Hayden, F.G. et al. (2020). "A novel coronavirus outbreak of global health concern". Lancet 395 (10223): 470–73. doi:10.1016/S0140-6736(20)30185-9. PMC PMC7135038. PMID 31986257. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135038. 
  4. ↑ Holshue, M.L.; DeBolt, C.; Lindquist, S. et al. (2020). "First Case of 2019 Novel Coronavirus in the United States". New England Journal of Medicine 382 (10): 929–36. doi:10.1056/NEJMoa2001191. PMC PMC7092802. PMID 32004427. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092802. 
  5. ↑ Bajema, K.L.; Oster, A.M.; McGovern, O.L. et al. (2020). "Persons Evaluated for 2019 Novel Coronavirus - United States, January 2020". Morbidity and Mortality Weekly Report 69 (6): 166–70. doi:10.15585/mmwr.mm6906e1. PMC PMC7017962. PMID 32053579. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017962. 
  6. ↑ Centers for Disease Control and Prevention. "COVIDView: A Weekly Surveillance Summary of U.S. COVID-19 Activity". Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html. Retrieved 03 July 2020. 
  7. ↑ World Health Organization. "Coronavirus disease (COVID-19) pandemic". World Health Organization. https://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/novel-coronavirus-2019-ncov. Retrieved 15 July 2020. 
  8. ↑ Hadfield, J.; Megill, C.; Bell, S.M. et al. (2018). "Nextstrain: Real-time tracking of pathogen evolution". Bioinformatics 34 (23): 4121-4123. doi:10.1093/bioinformatics/bty407. PMC PMC6247931. PMID 29790939. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247931. 
  9. ↑ 9.0 9.1 Elbe, S.; Buckland-Merrett, G. (2017). "Data, disease and diplomacy: GISAID's innovative contribution to global health". Global Challenges 1 (1): 33–46. doi:10.1002/gch2.1018. PMC PMC6607375. PMID 31565258. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607375. 
  10. ↑ Korber, B.; Fischer, W.M.; Gnanakaran, S. et al. (2020). "Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus". Cell S0092-8674 (20): 30820-5. doi:10.1016/j.cell.2020.06.043. PMC PMC7332439. PMID 32697968. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332439. 
  11. ↑ Bradburne, A.F.; Bynoe, M.L.; Tyrrell, D.A. (1967). "Effects of a "new" human respiratory virus in volunteers". British Medical Journal 3 (5568): 767–9. doi:10.1136/bmj.3.5568.767. PMC PMC1843247. PMID 6043624. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1843247. 
  12. ↑ Larson, H.E.; Reed, S.E.; Tyrrell, D.A. (1980). "Isolation of rhinoviruses and coronaviruses from 38 colds in adults". Journal of Medical Virology 5 (3): 221–9. doi:10.1002/jmv.1890050306. PMC PMC7167084. PMID 6262450. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167084. 
  13. ↑ Friedman, N.; Alter, H.; Hindiyeh, M. et al. (1980). "Human Coronavirus Infections in Israel: Epidemiology, Clinical Symptoms and Summer Seasonality of HCoV-HKU1". Viruses 10 (10): 515. doi:10.3390/v10100515. PMC PMC6213580. PMID 30241410. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213580. 
  14. ↑ Corman, V.M.; Landt, O.; Kaiser, M. et al. (2020). "Detection of 2019 Novel Coronavirus (2019-nCoV) by Real-Time RT-PCR". Euro Surveillance 25 (3): 2000045. doi:10.2807/1560-7917.ES.2020.25.3.2000045. PMC PMC6988269. PMID 31992387. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988269. 
  15. ↑ World Health Organization (19 February 2013). "Laboratory biorisk management for laboratories handling human specimens suspected or confirmed to contain novel coronavirus: Interim recommendations" (PDF). World Health Organization. https://www.who.int/csr/disease/coronavirus_infections/Biosafety_InterimRecommendations_NovelCoronavirus_19Feb13.pdf. Retrieved 11 May 2020. 
  16. ↑ Centers for Disease Control and Prevention. "Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 (COVID-19)". Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/lab/lab-biosafety-guidelines.html. Retrieved 11 May 2020. 
  17. ↑ 17.0 17.1 Lotfi, M.; Hamblin, M.R.; Rezaei, N. (2020). "COVID-19: Transmission, prevention, and potential therapeutic opportunities". Clinica Chimica Acta 508: 254–66. doi:10.1016/j.cca.2020.05.044. PMC PMC7256510. PMID 32474009. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256510.  Cite error: Invalid <ref> tag; name "LoftiCOVID20" defined multiple times with different content
  18. ↑ Lai, C.-C.; Liu, Y.H.; Wang, C,-Y. et al. (2020). "Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths". Journal of Microbiology, Immunology, and Infection 53 (3): 404–12. doi:10.1016/j.jmii.2020.02.012. PMC PMC7128959. PMID 32173241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128959. 
  19. ↑ Rothe, C.; Schunk, M.; Sothmann, P. et al. (2020). "Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany". New England Journal of Medicine 382 (10): 970-971. doi:10.1056/NEJMc2001468. PMC PMC7120970. PMID 32003551. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120970. 

Notes

This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added.

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