The United States Test Against COVID-19

On January 19, 2020,
a 35-year-old man with a 4-day historical past of cough, subjective fever, and up to date
journey historical past to Wuhan, China, introduced to an pressing care clinic in Snohomish
County, Washington. A well being alert from the United States Centers for Disease
Control and Prevention (CDC) relating to a novel coronavirus outbreak in China1
– along with his signs and journey historical past – prompted him to hunt
care. On January 20, 2020, the CDC
confirmed that samples from the affected person’s nasopharyngeal and oropharyngeal
swabs examined optimistic for that virus, now often known as extreme acute respiratory
syndrome coronavirus 2 (SARS-CoV-2), making this man the primary confirmed case
of the coronavirus illness of 2019 (COVID-19) within the United States.2,3

Close to three months
later, >1 million people within the United States have examined optimistic for SARS-CoV-2.5
This speedy unfold has been attributed to a variety of components together with the excessive
transmissibility of the virus,6,7 particularly amongst asymptomatic or
minimally symptomatic carriers;8,9 the obvious absence of any
cross-protective immunity from associated viral infections; and a delayed public
well being response.10,11,12

The total confirmed case quantity, nonetheless, is primarily a operate of the scope of testing, which depends on the case definition for COVID-19 and the variety of checks obtainable. Both components have proved to be a degree of rivalry because the virus continues its unfold all through the United States, and as a evaluate revealed in Annals of Internal Medicine identified, there’s a important want for ample, correct diagnostic testing within the face of this historic pandemic.13

Why Testing Matters

Until an efficient vaccine or therapy is out there, mitigating the unfold of a virus as infectious as SARS-CoV-2 requires taking steps to reduce transmission. The evaluate authors famous that these issues necessitate lowering the variety of folks uncovered to the virus in addition to lowering the fundamental reproductive quantity (R0) of the virus. This is most successfully completed by using excessive charges of testing for an infection. In the United States, neighborhood transmission started to happen earlier than ample testing measures have been applied. As such, Americans have been pressured to comply with a population-based mitigation technique for COVID-19 through measures akin to social distancing and stay-at-home orders. A sturdy testing technique, nonetheless, will help the United States’ to transition to the case-based mitigation technique seen in a variety of different international locations. This technique would enable for:


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  1. Detecting contaminated people. 
  2. Interrupting transmission via isolation of contagious people.
  3. Contact tracing of contaminated people to additional mitigate transmission.

In the medical setting, testing additionally aids in triage, allocation of non-public protecting gear, prevention of nosocomial infections and, as soon as obtainable, choices relating to therapy. This technique, nonetheless, is contingent on the varieties of checks obtainable, the assets required for testing, and turnaround time to outcomes. 

Early Concerns

The evaluate authors
spotlight that testing methods have various from nation to nation and are
contingent on each the general public well being assets obtainable in addition to the diploma
of viral unfold inside respective communities. 

Early in the midst of the outbreak, the one accepted take a look at for SARS-CoV-2 was the CDC assay developed beneath [EUA] from [FDA], which required samples to be despatched on to the CDC lab in Atlanta, Georgia.

In the United States,
testing was arguably sluggish to ramp up, a proven fact that has been attributed to a
slender testing indication, restricted testing capability, and regulatory hurdles for
growing and conducting checks.13,14,15 Early in the midst of the outbreak,
the one accepted take a look at for SARS-CoV-2 was the CDC assay developed beneath
Emergency Use Authorization (EUA) from the US Food and Drug Administration
(FDA), which required samples to be despatched on to the CDC lab in Atlanta,
Georgia. Kits developed by the CDC have been finally despatched to state and native
public well being laboratories to enhance entry and mitigate unfold, however shortly thereafter,
the CDC reported a number of labs had difficulties in validating outcomes attributable to a
defective reagent.16,17 As such, steering to ship samples instantly
to CDC remained, and considerations relating to scope and turnaround time for
confirming diagnoses continued. 

After delays in re-issuing validated CDC take a look at kits, the FDA sought to enhance entry to testing by asserting on February 29, 2020 that they might enable laboratories licensed to carry out high-complexity testing to “develop and begin to use validated COVID-19 diagnostics before the FDA [had] completed review of their [EUA] requests.” 18 By March 21, EUAs had been granted to >20 diagnostic checks and the variety of samples examined per day elevated from 32 to >44000.14 The FDA has continued to replace their approval course of; as of April 30, EUAs have been granted to >50 checks for SARS-CoV-2,19 testing capability has elevated to >230,000 per day,14 with >1 million Americans testing optimistic.4,5

Improving the Testing
Paradigm

Although real-time reverse transcriptase polymerase chain response (RT-PCR) based mostly assays of respiratory specimens have been the predominant mode of diagnostic testing within the United States, a variety of novel and complementary diagnostic methods are additionally being thought of. RT-PCR could be resource-intensive and sluggish; delays additionally put the contacts of sufferers beneath investigation in danger for an infection. As the evaluate authors famous, revolutionary testing methods akin to level of care testing, serologic testing, and residential specimen assortment, might assist expedite each the gathering and testing of specimen.

Point of Care Test

A low-complexity, speedy molecular diagnostic take a look at that may be performed on the level of care, thus not requiring a posh lab or specifically educated personnel, might be an vital device for mitigating the spread of COVID-19. On March 21, 2020, the FDA granted its first EUA to the Xpert Xpress SARS-CoV-2 point-of-care take a look at developed by Cepheid, which claims to supply outcomes 45 min.20

“Having
a take a look at that may let you know the illness you may have, however in 5 days is not going to assist
with choices about triage and the place you will put sufferers. We want an
reply rapidly, ideally we want a solution straight away, however any reply that’s in
lower than an hour is one thing that may be actionable,” famous David Alland, MD, MSc, whose staff has been working with Cephied to
validate their speedy level of care take a look at.

Having a take a look at that may let you know the illness you may have, however in 5 days is not going to assist with choices about triage and the place you will put sufferers. David Alland, MD, MSc
Chief of Infectious Disease
Rutgers New Jersey Medical School

Dr Alland, professor of
medication, chief of infectious illness, and the director of the Center for
Emerging Pathogens and the Rutgers Regional Biocontainment Laboratories at
Rutgers New Jersey Medical School, has been a pioneer within the analysis,
therapy, and molecular research of mycobacterium
tuberculosis
. He famous that “this is similar downside we had with drug
resistant tuberculosis [TB] 10, 20 years earlier than. We have been cohorting sufferers,
taking individuals who have been coming into the hospital to get higher and making them
worse as a result of they have been contaminated with a drug resistant type of TB.”

In the setting of
COVID-19, Dr Alland believes an analogous concern exists. Patients not contaminated
with SARS-CoV-2 requiring admission to a hospital might, inadvertently, fall in poor health
and presumably die on account of COVID-19. 

The FDA has since granted EUAs to three extra level of care checks for speedy detection of SARS-CoV-2.19 Although point-of-care checks usually are not meant to switch conventional RT-PCR checks performed in excessive throughput laboratories, they may doubtless play an vital position in important resolution making for sufferers. Moreover, they may help reduce the variety of healthcare staff being uncovered to the virus and doubtlessly falling in poor health. “In the immediate time frame, a point of care test is not going to help ‘flatten the curve.’ It is going to help keep patients and healthcare workers alive,” mentioned Dr Alland. “In the longer term, a point of care test that can go out and detect cases in the community can help ‘flatten the curve’ and help keep it flat.”  


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What can clinicians within the US accomplish with level of care testing? Listen to the Weekly Rounds’ dialogue, with additional perception from David Alland, MD, MSc, Professor of Medicine and the Chief of Infectious Disease at Rutgers New Jersey Medical School.

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…serological checks can play a important position within the struggle in opposition to COVID-19 by serving to healthcare professionals to establish people who’ve overcome an an infection up to now and have developed an immune response.Stephan M. Hahn, MD
FDA Commissioner

Serologic Test

Serologic checks analyze specimens, akin to blood or saliva, for the presence of antibodies, and may point out whether or not or not a person has mounted a response to an an infection quite than detect the virus itself. The evaluate authors warning that their utility in diagnosing acute infections is restricted, as antibody response to an infection can take days to weeks to be reliably detectable. Serologic assays could also be extra related in eventualities during which sufferers current with late issues of COVID-19 and RT-PCR could also be falsely destructive attributable to a lower in viral shedding.21  

In March 2020, the FDA issued a coverage permitting the builders of sure serologic checks to start administering them as soon as accuracy and reliability has been established.22 FDA Commissioner Stephan M. Hahn, MD famous in a press release that “serological tests can play a critical role in the fight against COVID-19 by helping healthcare professionals to identify individuals who have overcome an infection in the past and have developed an immune response.” He added that, “in the future, this may potentially be used to help determine, together with other clinical data, that such individuals are no longer susceptible to infection and can return to work.”22  

Serologic
testing may assist in epidemiologic research, ongoing surveillance, vaccine
research, and threat evaluation of well being care staff. 

Home Test

At current, there are not any residence testing kits accepted by the FDA. However on April 21, 2020 the FDA reissued the EUA for a RT-PCR assay developed by LabCorp for COVID-19, which permits for a house assortment choice of samples. “We worked with LabCorp to ensure the data demonstrated from at-home patient sample collection is as safe and accurate as sample collection at a doctor’s office, hospital or other testing site,” Dr Hahn remarked in a press release from the FDA.23

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Scaling Up Tests

EUAs have allowed for native public well being laboratories and tutorial diagnostic laboratories within the United States to quickly carry out assays for SARS-CoV-2. However, the authors of the Annals evaluate famous that will probably be vital to proceed advancing options that may be applied in much less well-equipped laboratories to mitigate the unfold of the pandemic on a world scale. Antigen-based checks, for instance, might show helpful in each low-resource and residential settings to information quarantine and social distancing measures, particularly amongst sufferers who’re mildly symptomatic. Further, novel diagnostic instruments akin to Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) might show helpful to nontraditional and resource-limited settings, akin to airports and border crossings. Finally, the evaluate authors emphasised that efforts needs to be made to leverage current surveillance networks. The CDC has already begun modifying current programs used to trace annual influenza infections and different respiratory viruses to observe the unfold of COIVD-19.24

Current Testing
Guidance

For clinicians who
could also be contemplating a take a look at for an individual beneath investigation, the CDC recommends
working with native and state well being departments to coordinate testing via
public well being laboratories; alternatively, they might use laboratory checks for
COVID-19 which have been granted an EUA by the FDA.25 

Clinicians are suggested to make use of their greatest judgment to find out whether or not or not a affected person has indicators and signs appropriate with a analysis of COVID-19 and whether or not the affected person needs to be examined. Tests for different causes of respiratory sickness needs to be thought of as wanted. At current, the CDC recommends COVID-19 precedence testing for: 

  • Hospitalized sufferers with shows appropriate
    with COVID-19, together with however not restricted to fever, cough, shortness of breath,
    chills, muscle ache, new lack of style or odor, vomiting or diarrhea or sore
    throat. [High]
  • Healthcare staff, staff in congregate residing
    settings, and first responders with signs. [High]
  • Residents in long-term care services or different
    congregate residing settings, together with prisons and shelters, with signs. [High]
  • Persons recognized via public well being clusters
    and chosen contact investigations. [High]
  • Individuals with signs of appropriate with
    COVID-19.
  • Individuals with out signs who’re prioritized by
    well being departments or clinicians, for any motive, together with however not restricted
    to:  public well being monitoring, sentinel surveillance, or screening of
    different asymptomatic people in response to state and native plans.

Recommended an infection prevention and management practices needs to be applied if a affected person is suspected of getting COVID-19. The CDC advises clinicians to inform an infection management personnel at their healthcare facility and their state or native well being division if a affected person is assessed as an individual beneath investigation for COVID-19. (Note: steering is topic to alter and the newest info could be discovered on the CDC’s page for evaluating and testing individuals with COVID-19)

Moving Forward

“Urgent medical and
public well being wants now drive an unprecedented international effort to extend
SARS-CoV-2 testing capability,” famous the evaluate authors in a concluding comment.
They emphasised that “the blinding velocity with which COVID-19 has unfold
illustrates the necessity for preparedness and long-term investments in diagnostic testing.”

…the flexibility to implement aggressive contact tracing, surveillance and testing might be basic to defending weak populations because the nation takes steps to reopen and Americans start returning to their each day lives. Robert R. Redfield, MD
CDC Director

Accordingly, the CDC
introduced on April 23, 2020 that they are going to be awarding $631 million to state
and native jurisdictions utilizing funds from the Coronavirus Aid, Relief and Economic
Security (CARES) Act of 2020,26 with the objective of:

  • Establishing or enhancing the
    skill to aggressively establish instances, conduct contact tracing and comply with up,
    and implement acceptable containment measures.
  • Improving morbidity and mortality
    surveillance.
  • Enhancing testing capability.
  • Controlling COVID-19 in high-risk
    settings and defending weak or high-risk populations.
  • Working with healthcare programs to
    handle and monitor system capability

Robert R. Redfield,
MD, director of the CDC, believes “this infusion of extra funding into the
nation’s public well being infrastructure will strengthen our capability to implement
tried and true containment measures.” He additionally famous that “the flexibility to
implement aggressive contact tracing, surveillance and testing might be
basic to defending weak populations because the nation takes steps to
reopen and Americans start returning to their each day lives.”26


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References

  1. Centers for Disease Control and Prevention. Outbreak of pneumonia of unknown etiology (PUE) in Wuhan, China. Updated January 8, 2020. Accessed May 1, 2020. https://emergency.cdc.gov/han/han00424.asp
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  8. Bai Y, Yao L, Wei T, et al. Presumed asymptomatic carrier transmission of COVID-19 [published online February 21, 2020]. JAMA. doi:10.1001/jama.2020.2565
  9. Li R, Pei S, Chen B, et al. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2). Science. doi:10.1126/science.abb3221
  10. Wells CR, Sah P, Moghadas SM, et al. Impact of international travel and border control measures on the global spread of the novel 2019 coronavirus outbreak. Proc Natl Acad Sci USA. 2020;117:7504-7509.
  11. Tuite AR, Bogoch II, Sherbo R, et al. Estimation of coronavirus disease 2019 (COVID-19) burden and potential for international dissemination of infection from Iran [published online March 16, 2020]. Ann Intern Med. doi:10.7326/M20-0696
  12. Lee VJ, Chiew CJ, Khong WX. Interrupting transmission of COVID-19: lessons from containment efforts in Singapore [published online March13, 2020]. J Travel Med. doi:10.1093/jtm/taaa039
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  16. Shear MD, Goodnough A, Kaplan S, Fink S, Thomas Okay, Weiland N. The lost month: how a failure to test blinded the U.S. to Covid-10. The New York Times. March 28, 2020. https://www.nytimes.com/2020/03/28/us/testing-coronavirus-pandemic.html?action=click&module=RelatedLinks&pgtype=Article. Accessed May 1, 2020.
  17. Weaver C, McKay B, Abott. America needed coronavirus tests. The government failed. The Wall Street Journal. March 19, 2020. https://www.wsj.com/articles/how-washington-failed-to-build-a-robust-coronavirus-testing-system-11584552147?mod=article_inline. Accessed May 1, 2020.
  18. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Issues New Policy to Help Expedite Availability of Diagnostics. Updated February 29, 2020. Accessed May 1, 2020. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-new-policy-help-expedite-availability-diagnostics
  19. Food and Drug Administration. Emergency use authorizations. Updated May 1, 2020. Accessed May 1, 2020. https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#covid19ivd
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This article initially appeared on Infectious Disease Advisor

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