The United States Test Against COVID-19

On January 19, 2020, a 35-year-old man with a 4-day history of cough, subjective fever, and recent travel history to Wuhan, China, bestowed to a pressing care clinic in Snohomish county, Washington. A health alert from the United States Centers for unwellnessControl and bar (CDC) regarding a novel coronavirus eruption in China – in conjunction with his symptoms and travel history – prompted him to seek care. On January 20, 2020, the CDC confirmed that samples from the patient’s cavity and cavity swabs tested positive for that virus, now best-known as severe acute metabolism syndrome coronavirus 2 (SARS-CoV-2), making this man the first confirmed case of the coronavirus unwellness of 2019 (COVID-19) in the United States

Close to 3 months later, >1 million individuals in the United States have tested positive for SARS-CoV-2. This rapid spread has been attributed to a number of factors including the high transmissibility of the virus, especially among symptomless or minimally symptomatic carriers; the apparent absence of any cross-protective immunity from related microorganism infections; and delayed public health response.

The overall confirmed case number, nevertheless, is primarily a function of the scope of testing, which is dependent on the case definition for COVID-19 and the number of tests available. some factors have proven to be a point of contention as the virus continues its spread throughout the United States, and as a review published in Annals of Internal Medicine pointed out, there is a critical need for ample, accurate diagnostic testing in the face of this historic pandemic.

Why Testing Matters

Until an effective vaccinum or treatment is available, mitigating the spread of a virus as infectious as SARS-CoV-2 requires taking steps to minimize transmission. The review authors noted that these considerations necessitate reducing the number of people exposed to the virus as well as reducing the basic generative number (R) of the virus. This is most effectively accomplished by employing a high tax of testing for infection. In the United States, community transmission began to occur before adequate testing measures were enforced. As so much, Americans were forced to follow a population-based mitigation strategy for COVID-19 via measures so much as social distancing and stay-at-home orders. A robust testing strategy, nevertheless, will support the United States’ to transition to the case-based mitigation strategy seen in a number of other countries. This strategy would allow for:

1. Detecting septic individuals.
2. Interrupting transmission through isolation of contagious individuals.
3. Contact tracing of septic individuals to further mitigate transmission.

In the clinical setting, testing besides AIDS in sorting, allocation of personal protective instrumentality, a bar of medical building infections, and, once available, decisions regarding treatment. This strategy, nevertheless, is contingent on the types of tests available, the resources required for testing, and turnaround time to results.

Early Concerns

The review authors highlight that testing strategies have varied from country to country and are contingent on some of the public health resources available as well as the degree of microorganism spread inside several communities.

Early in the course of the eruption, the only approven test for SARS-CoV-2 was the CDC assay developed under [EUA] from [FDA], which required samples to be sent directly to the CDC lab in Atlanta, Georgia.

In the United States, testing was arguably slow to ramp up, a fact that has been attributed to a narrow testing indication, limited testing capacity, and regulative hurdling for developing and conducting tests. Early in the course of the eruption, the only approved test for SARS-CoV-2 was the CDC assay developed under emergency Use Authorization (EUA) from the US Food and Drug Administration(FDA), which required samples to be sent directly to the CDC lab in Atlanta, Georgia. Kits developed by the CDC were eventually sent to state and local public health laboratories to improve access and mitigate spread, but shortly thereafter, the CDC according to several labs had difficulties in collateral results due to a faulty reagent. As so much, guidance to send samples directly to CDC remained, and concerns regarding scope and turnaround time for confirming diagnoses persisted.

After delays in re-issuing valid CDC test kits, the FDA sought-after to improve access to testing by announcing on February 29, 2020, that they would allow laboratories certified to perform high-complexity testing to “develop and begin to use valid COVID-19 nosology before the FDA [had] completed a review of their [EUA] requests.” By March 21, EUAs had been granted to >20 diagnostic tests, and the number of samples tested per day accrued from 32 to >44000. The FDA has continuing to update its approval process; as of April 30, EUAs have been granted to >50 tests for SARS-CoV-2, testing capacity has accrued to >230,000 per day, with >1 million Americans testing positive.

Improving the TestingParadigm

Although time period reverse enzyme chain reaction (RT-PCR) based assays of metabolism specimens have been the predominant mode of diagnostic testing in the United States, a number of novel and complementary diagnostic strategies are besides being considered. RT-PCR can be resource-intensive and slow; delays besides put the contacts of patients under investigation at risk for infection. As the review authors noted, innovative testing strategies so much as a point of care testing, serologic testing, and home specimen collection, may help expedite some of the collection and testing of specimens.

Point of Care Test

A low-complexity, rapid molecular diagnostic test that can be conducted at the point of care, thus not requiring a complex lab or specially trained personnel, will be an important tool 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 test developed by Cepheid, which claims to provide results 45 min.²⁰

“Having a test that will tell you the unwellness you have, but in 5 years will not help with decisions about sorting and where you are going to put patients. We need an answer quickly, ideally we need an answer right away, but any answer that is in less than an hour is the thing that can be actionable,” noted David Alland, MD, MSc, whose team has been working with Cepheid to validate their rapid point of care test.

Having a test that will tell you the unwellness you have, but in 5 years will not help with decisions about sorting and where you are going to put patients.

David Alland, MD, MSc
Chief of Infectious unwellness
Rutgers New Jersey Medical School

Dr. Alland, prof of medicine, chief of infectious unwellness, 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 in the diagnosing, treatment, and molecular study of mycobacterium TB. He noted that “this is the same problem we had with drug-resistant TB [TB] 10, 20 years before. We were cohorting patients, taking people who were coming into the hospital to get better and making them worse because they were septic with a drug-resistant form of TB.”

In the setting of COVID-19, Dr. Alland believes a similar concern exists. Patients not septic with SARS-CoV-2 requiring admission to a hospital may, unwittingly, fall ill and possibly die as a result of COVID-19.

The FDA has since granted EUAs to 3 extra points of care tests for rapid observation of SARS-CoV-2. Although point-of-care tests are not meant to replace traditional RT-PCR tests conducted in high output laboratories, they will likely play an important role in critical decision making for patients. furthermore, they can help minimize the number of health care workers being exposed to the virus and possibly falling ill. “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 health care workers alive,” aforesaid Dr. Alland. “In the thirster term, a point of care test that can go out and observe cases in the community can help ‘flatten the curve’ and help keep it flat.”

…serological tests can play a critical role in the fight against COVID-19 by portion health care professionals to identify individuals who have overcome an infection in the past and have developed an immune response.

Stephan M. Hahn, MD
FDA Commissioner

serologic Test

serologic tests analyze specimens, so much as blood or spit, for the presence of antibodies, and can indicate whether or not an individual has mounted a response to an infection rather than observe the virus itself. The review authors caution that their utility in diagnosing acute infections is limited, as protein response to infection can take years to weeks to be faithfully observable. serologic assays may be more applicable in scenarios in which patients present with late complications of COVID-19 and RT-PCR may be incorrectly negative due to a decrease in microorganism shedding.

In March 2020, the FDA issued a policy allowing the developers of certain serologic tests to begin administering them once accuracy and dependability has been established. FDA Commissioner Stephan M. Hahn, MD noted in a statement that “serological tests can play a critical role in the fight against COVID-19 by portion health care professionals to identify individuals who have overcome infection in the past and have developed an immune response.” He added that, “in the future, this may possibly be used to help determine, together with other clinical information, that so many individuals are no thirster susceptible to infection and can return to work.”

serologic testing may besides aid in epidemiologic studies, on-going police work, vaccine studies, and risk assessment of health care workers.

Home Test

At present, there are no home testing kits approved by the FDA. nevertheless on April 21, 2020 the FDA reissued the EUA for an RT-PCR assay developed by LabCorp for COVID-19, which allows for a home collection option of samples. “We worked with LabCorp to ensure the information incontestable from at-home patient sample collection is as safe and accurate as sample collection at a doctor’s office, hospital, or another testing site,” Dr. Hahn remarked in a statement from the FDA.

Scaling Up Tests

EUAs have allowed for local public health laboratories and academic diagnostic laboratories in the United States to quickly perform assays for SARS-CoV-2. nevertheless, the authors of the Annals review noted that it will be important to continue advancing solutions that can be enforced in less well-equipped laboratories to mitigate the spread of the pandemic on a global scale. Antigen-based tests, for example, may prove useful in some low-resource and home settings to guide quarantine and social distancing measures, especially among patients who are gently symptomatic. Further, novel diagnostic tools so much as Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) may prove useful to untraditional and resource-limited settings, so much as airports and border crossings. Finally, the review authors emphasize that efforts should be made to leverage existing police work networks. The CDC has not yet begun modifying existing systems used to track annual flu infections and other metabolism viruses to monitor the spread of COIVD-19.

Current TestingGuidance

For clinicians who may be considering a test for a person under investigation, the CDC recommends working with local and state health departments to coordinate testing through public health laboratories; as an alternative, they may use laboratory tests forCOVID-19 that have been granted a EUA by the FDA.

Clinicians are advised to use their best judgment to determine whether or not a patient has signs and symptoms compatible with a diagnosis of COVID-19 and whether the patient should be tested. Tests for other causes of metabolism unwellness should be considered as needful. At present, the CDC recommends COVID-19 priority testing for:

• Hospitalized patients with presentations compatible with COVID-19, including but not limited to fever, cough, shortness of breath, chills, muscle pain, the new loss of taste or smell, vomit or diarrhea or sore throat. [High]
• Healthcare workers, workers in congregate living settings, and first responders with symptoms. [High]
• Residents in long-run care facilities or other congregate living settings, including prisons and shelters, with symptoms. [High]
• Persons are known through public health clusters and chosen contact investigations. [High]
• Individuals with symptoms of compatible withCOVID-19.
• Individuals without symptoms who are prioritized by health departments or clinicians, for any reason, including but not limited to public health observation, lookout police work, or screening of other symptomless individuals according to state and local plans.

Recommended infection bar and control practices should be enforced if a patient is unsuspected of having COVID-19. The CDC advises clinicians to advise infection control personnel at their health care facility and their state or local health department if a patient is classified as a person under investigation for COVID-19. (Note: the guidance is subject to change and the latest information can be found on the CDC’s page for evaluating and testing persons with COVID-19)

Moving Forward

“Urgent clinical and public health inevitably now drive a new global effort to increase SAR-CoV-2 testing capacity,” noted the review authors in a final remark. They emphatic that “the blazing speed with which COVID-19 has spread illusttax the need for readiness and long-run investments in diagnostic testing.”

…the ability to implement aggressive contact tracing, police work and testing will be fundamental to protective vulnerable populations as the nation takes steps to open and Americans begin returning to their daily lives.

Robert R. Redfield, MD
CDC Director

Accordingly, the CDC announced on April 23, 2020, that they will be award $631 million to state and local jurisdictions exploitation finances from the Coronavirus Aid, Relief and EconomicSecurity (CARES) Act of 2020,²⁶ with the goal of:

• Establishing or enhancing the ability to sharply identify cases, conduct contact tracing and follow up, and implement appropriate containment measures.
• Improving morbidity and morality police work.
• Enhancing testing capacity.
• Controlling COVID-19 in bad settings and protect vulnerable or bad populations.
• Working with health care systems to manage and monitor system capacity

Robert R. Redfield, MD, director of the CDC, believes “this infusion of extra funding into the nation's public health infrastructure will strengthen our capacity to implement tried and true containment measures.” He besides noted that “the ability to implement aggressive contact tracing, police work, and testing will be fundamental to protect vulnerable populations as the nation takes steps to open and Americans begin returning to their daily lives.