COVID-19: A Review of the Evolving Science and Current CDC - - PDF document

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COVID-19: A Review of the Evolving Science and Current CDC - - PDF document

COVID-19: A Review of the Evolving Science and September 14, 2020 Current CDC Guidance COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 1 1 Welcome Martha DeCastro, MS, RN Vice President for Nursing


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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 1

COVID-19: A Review of the Evolving Science and Current CDC Guidance

September 14, 2020

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Welcome

Martha DeCastro, MS, RN Vice President for Nursing and Clinical Care Policy Florida Hospital Association

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 2

Presenters

David Cook, MD

  • Dr. David Cook’s research focuses on human malaria clinical trials at the

National Institutes of Health, Laboratory of Malaria Immunology and Vaccinology (LMIV) at NIAID. His research focus is on malaria vaccines in

  • humans. Before taking a position with NIH, Dr. Cook completed his Infectious

Disease training at the NIH Clinical Center in 2019. He received his medical degree from the Uniformed Services University and is originally from Idaho. Neha Shah, MD, MPH

  • Dr. Neha Shah’s work focuses on tuberculosis and HIV clinical trials at

National Institutes of Health, Division of AIDS at NIAID. Her research focuses

  • n tuberculosis therapeutics and vaccines. Before taking a position with NIH,
  • Dr. Shah worked for the CDC and was part of CDC’s EIS (Epidemic

Intelligence Service) from 2007-2009. She then served as the Medical Director

  • f Tuberculosis in Chicago from 2009-2011 and then went on to be the director
  • f California’s TB Free initiative until she moved to the NIH in 2019.

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COVID-19: Update on Evidence and Guidelines for Testing and Reinfection

David Cook, MD Neha Shah, MD MPH September 14, 2020

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 3

Disclaimer

  • The findings and conclusions in this presentation are those of the authors
  • The information in this presentation is current as of September 8, 2020

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Overview of presentation

  • COVID testing
  • Recent CDC guideline updates
  • Re-infection

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 4

Testing for COVID

What types of tests are there?

  • Antibody
  • Antigen
  • PCR

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 5

Antibody (indirect) testing

What is the difference between an antibody and an antigen test?

Republic reporting; illustration by Nicole Schaub

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 6

What do COVID-19 antibody and antigen tests detect?

Daniel Wrapp et al. Science 2020;367:1260-1263

SARS-CoV-2 Antibody Tests

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 7

Antibodies can be detected week 2

  • Peak week 3
  • IgG persists

Sethuraman et al, JAMA 2020

Two months after symptom onset, IgG still elevated among inpatients

Katharina Roeltgen Oliver Wirz Stanford https://www.youtube.com/watch?v=rd9kpT-TaJM&t=2317s

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 8

More rapid decrease in asymptomatic outpatients

Katharina Roeltgen Oliver Wirz Stanford https://www.youtube.com/watch?v=rd9kpT-TaJM&t=2317s

Lower antibodies levels among those with higher cycle thresholds

Saurabh Gombar Stanford https://www.youtube.com/watch?v=rd9kpT-TaJM&t=2317s

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 9

Unsure how long antibodies last

Gudbjartsson; September 1, 2020 DOI: 10.1056/NEJMoa2026116

Sensitivity and specificity varies during course of infection

Deeks, Cochrane Systematic Review - Diagnostic Version published: 25 June 2020

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 10

Sensitivity and specificity varies during course of infection

Deeks, Cochrane Systematic Review - Diagnostic Version published: 25 June 2020

Sensitivity and specificity varies during course of infection

Deeks, Cochrane Systematic Review - Diagnostic Version published: 25 June 2020

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 11

Sensitivity and specificity varies during course of infection

Deeks, Cochrane Systematic Review - Diagnostic Version published: 25 June 2020

Sensitivity and specificity varies during course of infection

Deeks, Cochrane Systematic Review - Diagnostic Version published: 25 June 2020

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 12

Antibody testing is helpful for surveillance

  • Not ideal for diagnosis as are not detectable until later in infection
  • Great to help understand current population prevalence
  • Demographic and geographic patterns can identify communities who

experienced a higher infection rate

  • Identify individuals who can donate convalescent plasma treatment

Antigen testing

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 13

What about using antigen tests instead of PCR?

  • Antigen tests detect proteins on the virus
  • Antigen tests can tell you if someone is currently infected

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 14

Advantages to antigen tests

  • Cheaper
  • Rapid
  • More amenable to point-of-care use
  • Nasopharyngeal or nasal swab

Limitations include limit of detection

Lateral Flow

https://www.youtube.com/watch?v=kNADw5io9Ms&t=448s

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 15

Could be used as screening tool if done frequently

  • Screening in high-risk

congregate settings where infection prevention and control measures can be implemented immediately

  • Requires frequent testing with

no delays in reporting

Larremore: doi.org/10.1101/2020.06.22.20136309 More available at: https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html

PCR/NAAT

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Hadaya J, Schumm M, Livingston EH. Testing Individuals for Coronavirus Disease 2019 (COVID-19). JAMA. 2020;323(19):1981. doi:10.1001/jama.2020.5388

Viral culture

Harcourt J, Tamin A, Lu X, et al. Severe Acute Respiratory Syndrome Coronavirus 2 from Patient with Coronavirus Disease, United States. Emerging Infect Dis. 2020;26(6):1266-1273. doi:10.3201/eid2606.200516.

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Updated CDC guidelines: Shift to symptom-based strategy

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 18

  • n = 9
  • Cluster detected in January 2020
  • Single hospital in Munich, Germany
  • RT– PCR and viral culture results were cross-confirmed in two laboratories
  • Participants not stratified by disease severity

Wölfel R, Corman VM, GuggemosW, et al. Virologicalassessment of hospitalized patients with COVID-2019. Nature. May 2020:1-12. doi:10.1038/s41586-020-2196-x. Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. May 2020:1-12. doi:10.1038/s41586-020-2196-x.

The likelihood of recovering replication-competent virus declines after onset of symptoms

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  • n = 12
  • January - February 2020 in six US states
  • SARS-CoV-2 RT-PCR and viral culture
  • Mild to moderately severe illness
  • No positive viral cultures after day 9 post-symptom onset

Kujawski SA, Wong KK, Collins JP, et al. Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States. Nature Medicine. June 2020:1-23. doi:10.1038/s41591-020-0877-5.

  • n = 90
  • Public health lab in Manitoba, Canada
  • No viral culture were isolated 7 days after symptom onset

Bullard J, Dust K, Funk D, et al. Predicting infectious SARS-CoV-2 from diagnostic samples. Clin Infect Dis. May 2020. doi:10.1093/cid/ciaa638.

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Bullard J, Dust K, Funk D, et al. Predicting infectious SARS-CoV-2 from diagnostic samples. Clin Infect Dis. May 2020. doi:10.1093/cid/ciaa638.

  • n = 89
  • Survey of nursing home in Washington State in March 2020
  • RT-PCR+ in 48 individuals, followed by viral cultures
  • No viral cultures positive after day 9 post symptom onset

Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility. N Engl J Med. 2020;382(22):2081-2090. doi:10.1056/NEJMoa2008457.

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Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility. N Engl J Med. 2020;382(22):2081-2090. doi:10.1056/NEJMoa2008457.

  • February and March 2020
  • Infection diseases reference lab in France
  • Of 4384 tested samples, 183 (in 155 unique individuals) were positive by

RT-PCR

  • No positive cultures after day 8 in spite of ongoing high viral loads

La Scola B, Le Bideau M, Andreani J, et al. Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards. May 2020:1-3. doi:10.1007/s10096-020-03913-9.

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  • n = 129
  • March - April 2020 in Rotterdam, the Netherlands
  • Severe or critical COVID-19 (89 intensive care, 40 intermediate care)
  • SARS-CoV-2 PCR and viral culture
  • Duration of infectious virus shedding ranged from 0 to 20 days post onset
  • f symptoms

van Kampen JJA, van de Vijver DAMC, Fraaij PLA, et al. Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID-19): duration and key

  • determinants. medRxiv. June 2020:1-28. doi:10.1101/2020.06.08.20125310.

van Kampen JJA, van de Vijver DAMC, Fraaij PLA, et al. Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID-19): duration and key

  • determinants. medRxiv. June 2020:1-28. doi:10.1101/2020.06.08.20125310.

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 23

  • Prospective case-ascertained study in Taiwan included laboratory-

confirmed cases of COVID-19 and their contacts

  • January 15 to March 18, 2020
  • All close contacts were quarantined at home for 14 days after their last

exposure to the index case

  • Enrolled 100 confirmed patients and 2761 close contacts

Cheng H-Y, Jian S-W, Liu D-P, et al. Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset. JAMA Intern Med. May 2020:1-8. doi:10.1001/jamainternmed.2020.2020.

High-risk household and hospital contacts did not develop infection if their exposure to a case patient started 6 days or more after the case patient’s illness onset

Cheng H-Y, Jian S-W, Liu D-P, et al. Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset. JAMA Intern Med. May 2020:1-8. doi:10.1001/jamainternmed.2020.2020.

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 24

Summary – window of infectivity after symptom onset

  • Available data indicate that persons with mild to moderate COVID-19

remain infectious no longer than 10 days after symptom onset.

  • Persons with more severe to critical illness or severe immunocompromise

likely remain infectious no longer than 20 days after symptom onset.

https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html

Caveats

  • In a recent study of skilled nursing facility workers followed prospectively

for asymptomatic infection, one of 48 infected staff had a nasopharyngeal swab which was weakly positive on a single-passage plaque assay more than 20 days after initial diagnosis; however, the specimen was not subjected to serial passage to demonstrate the presence of replication- competent virus (Quicke et al., 2020).

  • In one case report, a person with mild illness provided specimens that

yielded replication-competent virus for up to 18 days after symptom onset (Liu et al., 2020).

  • Data currently available are derived from adults; equivalent data from

children and infants are not presently available.

  • More data are needed concerning viral shedding in some situations,

including in immunocompromised persons.

https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 25

Recommendations

  • For most persons with COVID-19 illness, isolation and precautions can

generally be discontinued 10 days after symptom onset and resolution of fever for at least 24 hours, without the use of fever-reducing medications, and with improvement of other symptoms.

  • A limited number of persons with severe illness may produce replication-

competent virus beyond 10 days that may warrant extending duration of isolation and precautions for up to 20 days after symptom onset; consider consultation with infection control experts.

  • For persons who never develop symptoms, isolation and other precautions

can be discontinued 10 days after the date of their first positive RT-PCR test for SARS-CoV-2 RNA.

https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html

Recommendations

  • For persons who are severely immunocompromised, a test-based strategy

could be considered in consultation with infectious diseases experts.

  • For all others, a test-based strategy is no longer recommended except to

discontinue isolation or precautions earlier than would occur under the strategy outlined above.

https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html

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Re-infection

https://www.cdc.gov/media/releases/2020/s0814-updated-isolation-guidance.html

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COVID-19: A Review of the Evolving Science and Current CDC Guidance September 14, 2020 Florida Hospital Association 27

  • Korean CDC investigated performed contact tracing for 285 index cases of

individuals who had symptomatically recovered from COVID but again tested positive

  • 790 contacts were identified, with only 3 new cases detected among those

contacts

  • All of the 3 newly confirmed cases had a history of contact with the

Shincheonji religious group or another confirmed case in their family

Korea Centers for Disease Control and Prevention. Findings from Investigation and Analysis of re-positive cases. May 19, 2020. Available at: https://www.cdc.go.kr/board/board.es?mid=a30402000000&bid=0030&act=view&list_no=367267&nPage=1

Recovered patients can continue to have SARS-CoV-2 RNA detected in their upper respiratory specimens for up to 12 weeks

Korea Centers for Disease Control and Prevention. Findings from Investigation and Analysis of re-positive cases. May 19, 2020. Available at: https://www.cdc.go.kr/board/board.es?mid=a30402000000&bid=0030&act=view&list_no=367267&nPage=1

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  • Prospective survey of viral etiologies of pneumonia in Kilifi, Kenya
  • Found that initial infection with non-SARS-CoV-2 human coronaviruses

(HCoV-229E, HCoV-NL63, and HCoV-OC43) did not lead to decrease in likelihood of re-infection after 3 months

Kiyuka PK, Agoti CN, Munywoki PK, et al. Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya. The Journal of Infectious

  • Diseases. 2018;217(11):1728-1739. doi:10.1093/infdis/jiy098.

Summary - Testing for suspected re-infection

  • Reinfection has not been definitively confirmed in recovered persons to date.
  • No evidence to date that clinically recovered persons with persistence of viral RNA

have transmitted SARS-CoV-2 to others.

  • A positive PCR during the 90 days after illness onset more likely represents

persistent shedding of viral RNA than reinfection.

  • Re-testing within 90 days of symptom onset is unlikely to yield useful information in

an asymptomatic person, even if the person had close contact with an infected person.

  • If a person becomes symptomatic within 90 days they may warrant re-testing and

isolation, particularly if symptoms developed after close contact with an infected person.

https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html

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Recommendations

  • For persons previously diagnosed with symptomatic COVID-19 who remain

asymptomatic after recovery, retesting is not recommended within 3 months after the date of symptom onset for the initial COVID-19 infection. In addition, quarantine is not recommended in the event of close contact with an infected person.

  • For persons who develop new symptoms consistent with COVID-19 during

the 3 months after the date of initial symptom onset, if an alternative etiology cannot be identified by a provider, then the person may warrant retesting.

  • For persons who never developed symptoms, the date of first positive RT-

PCR test for SARS-CoV-2 RNA should be used in place of the date of symptom onset.

https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html

Recommendations

  • Serologic testing should not be used to establish the presence or absence
  • f SARS-CoV-2 infection or reinfection.

https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html

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Summary

Summary

  • Testing

– Several different types of testing – Most sensitive if PCR testing – Quickest is antigen testing

  • CDC symptom-based recommendations

– No longer need two tests 59 60

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Summary

  • Reinfection

– Unknown if this is possible – Some limited data showing some people have gotten re-infected

Questions?

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Thank you!

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