Background
Testing for SARS-CoV-2 is important for multiple reasons. At the clinical level, when someone has COVID-like symptoms, it is important to find out whether they have COVID-19 or something else, in order to provide effective treatment. To prevent COVID-19 spread, it is important to test hospital and nursing home staff and visitors, so they do not infect frail elderly high-risk individuals. It is also important for disease surveillance and sero-prevalence estimation. This latter topic is covered in Chapter 5 on Public Health Data.
As early as February 2020, public health agencies emphasized testing in combination with contact tracing as interventions to suppress COVID-19 spread. To the extent that this was a policy position, large-scale rapid testing was needed. When it became clear COVID-19 could not be eradicated, testing was still important to guide treatment and to protect those who were at high risk of severe disease. However, testing continued to be used and recommended for the general population, including in very low risk children, without evidence of individual or community-wide benefit from doing so. Positive tests forced children to miss school and adults to miss work without evidence of these strategies effectively decreasing community transmission or benefiting the health of the community.
COVID-19 testing in the U.S. was marked by periods of significant under-testing, over-testing, and socioeconomic inequities in access to testing due to hoarding of tests by wealthy institutions such as elite universities.
Development, Approval, and Production of COVID-19 Tests
Because SARS-CoV-2 was a novel pathogen, COVID-19 tests were not available at the beginning of the pandemic. For the purposes described above, it was important to quickly develop, evaluate, and approve such tests and get them to market.
The SARS-CoV-2 viral genome sequence was made available worldwide on January 10th, 2020. On January 23, 2020, Europe released the first diagnostic PCR test and rapidly shipped worldwide to 57 countries by the end of February. However, the US declined to use it, stalling testing here for around 6 weeks. While millions of tests were performed weekly across the developed world, the US had only done 549 tests by February 28, 2020 because the CDC declined PCR “recipes” available from the WHO and China, choosing instead to develop its own test. This led to health-care facilities facing test shortages. After the CDC developed its own COVID-19 test, the agency was slow to distribute it to state and local health departments.
While other countries quickly established working PCR assays to identify the virus in patient samples, after February 4th, when the state of emergency was declared, laboratories in the U.S. were not permitted to replicate these tests. After this date, laboratories were required to gain FDA approval to run tests, severely delaying the ability to identify cases and attempts to limit spread. This is because of a pre-pandemic regulation stating that, in a state of emergency, the FDA regulates who is approved to conduct pathogen testing. This strict FDA policy slowed development of new PCR tests by university laboratories and commercial vendors.
Why did the US decline to use the validated European test when it became available or to use the WHO test?
How many health-care facilities lacked sufficient tests? How many suspected positive patients were denied treatment?
Why was this FDA regulation not amended? Why were pathways to deliver testing not smoothed quickly, nor regulatory burdens removed?
How many lives of nursing home residents and other elderly high risk could have been saved by more rapid deployment/use/creation of tests during the 6 weeks that the US lagged the rest of the developed world?
Testing in Hospitals and Nursing Homes
Testing staff in hospitals and nursing homes is important to minimize the risk that staff unwittingly infect older frail and other high-risk patients and residents. When tests were in short supply, testing in high-risk populations was not prioritized. Particularly early on, when restrictions on testing had not been lifted, the CDC failed to surge tests to the most high-risk populations such as long-term care patients and their caregivers. Instead, many tests were used on close contacts of patients, even when those contacts were low risk and not in danger of infecting high-risk populations.
Why did the CDC fail to roll out to governors and state health departments a testing distribution strategy that prioritized the highest risk populations, older people, long term care patients and their caregivers, and hospital patients? Did sub-optimal use of limited resources result in unnecessary nursing home and long-term care facility deaths?
During the spring and summer of 2020, there was limited testing of nursing home staff. Why was that? Was there a shortage of available tests? Were there regional differences in testing availability?
In the fall of 2020, testing frequency at nursing homes increased. How did this come about? Where did the resources come from? Could it have happened earlier?
Mass Asymptomatic Testing of Low-Risk Populations
COVID-19 tests have been widely used for mass testing asymptomatic individuals in schools, universities, and workplaces, but there have been very few attempts to measure the efficacy of such testing. One study, conducted prior to the Delta wave in the spring of 2021 and published in April 2022, showed that weekly asymptomatic testing in schools did little to reduce viral spread either in schools or in the community. Several studies show dwindling sensitivity of antigen tests at recognizing new variants; antigen tests remain particularly inaccurate at detecting infection in the absence of symptoms. Despite this, many schools continued to conduct asymptomatic surveillance testing at the behest of the CDC at enormous great expense of money and staff time, and causing test-positive students and staff and their close contacts to be excluded from school, all without giving adequate consideration to the limitations (false positives or negatives) and downsides of these tests.
In light of the above, why did the CDC stress that mass asymptomatic testing was a vital part of a strategy to reduce viral spread in schools and universities through August of 2022, especially when numerous European countries had largely abandoned mass testing of children? Was the purpose of continued testing in K-12 schools to reassure parents and teachers that in person learning was “safe” despite a lack of data to support this intervention and without acknowledging the drawbacks of lost school days?
Was the continued push for testing of low-risk individuals in the US a result of lobbying from testing companies? Were some of those pushing mass testing financially benefiting from testing companies?
Why did most universities insist on testing low-risk asymptomatic students, sometimes as much as three times per week? Did White House officials and CDC officials urge them to do so? Did they do it because of fear of litigation?
Why did the CDC or NIH not conduct group randomized trials to determine whether mass asymptomatic testing in schools and universities had any positive effect?
Test accuracy is lower for the omicron variant. Why was/is mass testing still recommended in some places even with decreasing accuracy of the tests?
What is the decision-making process that goes into determining when to discontinue a policy such as asymptomatic testing in schools and universities when data supporting its use have not been generated?
In late 2021 and early 2022, the CDC issued broad testing recommendations while there was a limited testing supply. As a result, a testing grab ensued, with wealthier and more powerful communities securing tests for low-risk Americans while poor and minority communities struggled to get tests. Why did the CDC recommend mass testing while COVID-19 tests were in scarce supply? Why was the testing guidance not modified so that the limited number of tests available were rationed wisely?
Contact Tracing
Testing and contact tracing is important for containing many infectious diseases, such as sexually transmitted diseases, but it is ultimately futile for reducing the spread of respiratory diseases such as influenza or SARS-CoV2 that have an infectious period during an asymptomatic or mildly symptomatic phase. Furthermore, by the time COVID-19 tests were widely available, the disease was widespread across the globe, as already demonstrated in April of 2020, and not amenable to eradication by quarantine. Also, COVID-19 can infect multiple species of animals, making it even more unlikely it could ever be eradicated, even if it had been possible to quarantine all infected humans (which it was not). In 2021, for example, surveillance studies showed that SARS-CoV-2 was present in white tailed deer.
Why did federal and state governments spend large amounts of effort and money on futile testing and contact tracing activities? Why were funds not instead prioritized for more important activities, such as increased testing in nursing homes, better ventilation in schools, or ensuring that older high-risk people did not have to work in high-risk occupations such as taxi drivers or store clerks?
In early 2021, when the New York City Department of Health asked Dr. Fauci to divert federal funds from contact tracing to vaccine delivery, what was the reaction from the federal government? How many state and local health departments lacked sufficient resources for vaccine delivery to older high-risk Americans while federal funds were earmarked for contact tracing?
Testing for Travel
Until June 2022, the United States required pre-departure testing for air-travel into the country, and after that, for unvaccinated travelers. The CDC stated that the policy’s goals were to preserve human life; prevent spread and introduction of new variants; keep airline crew, passengers, and personnel safe; and preserve healthcare resources. Notably, domestic airline travel, of which there is significantly more than international travel, required no such testing, nor did international arrivals via land or water.
Why did the CDC require testing for international air travel, but not for domestic?
Why did the CDC require testing for international arrivals by air, but not by land or sea?
In 2015, the CDC evaluated effectiveness of border entry screening during the SARS1 and H1N1 influenza outbreaks, and concluded that both were heavily resource intensive, unlikely to be successful in preventing entry of disease, and should not be used. Why did the CDC not follow its 2015 conclusions?
Rapid antigen tests are not reliable early during an infection, which alone rendered the intervention aimed at a highly transmissible virus futile. Furthermore, the rapid spread of omicron around the world, including in the USA, after its discovery in South Africa in November 2021, at a time when arrival testing was in heavy use internationally, clearly demonstrated that such testing programs were not effective and spread of the variant was inevitable. Nearly all countries dropped air travel testing requirements before the US did in June of 2022. Why was international pre-departure testing required for so long for entry into the US?
Why was so little consideration given to the harms of such a futile intervention, such as the negative impacts on travel and tourism which many cities rely upon for revenue, or the fact that many Americans living abroad were denied the last opportunity to be with loved ones? Why was a principle so fundamental to public health as Bayes’ Theorem ignored, which states that the utility of a diagnostic test dwindles as the likelihood of a tested person being positive decreases?
Home Testing
Home testing has been an effective strategy to enable rapid results when people want to know if they can safely visit an older relative. The medical profession has a long history of resisting home testing, evidenced by resistance to home pregnancy tests for women, which were not available until 1977 despite being developed in the 1920s. Similar resistance delayed the introduction of home HIV tests.
The FDA first authorized a home COVID-19 self-test on Nov. 17, 2020, but at-home tests were not widely available for home and business use until early 2022. During the omicron surge of 2021, test supply did not meet demand. Why did public health officials take so long to embrace home COVID-19 testing and stall in providing tests to the places they were needed most?
In the late winter and early spring, when Europe had widespread access to free COVID-19 tests, there was a serious supply shortage in the US through winter of 2021; available tests were expensive and difficult to find, again placing the poor at higher risk of exposure and continuing isolation for the elderly with fewer resources. What were the primary drivers of the shortage?
Polymerase Chain Reaction Test Cycle Thresholds
Nucleic acid amplification tests, such as polymerase chain reaction (PCR) tests, are used to detect the presence of SARS-CoV-2 genetic material in individual samples. However, a positive result does not indicate the presence of live virus or an ability of a positive person to transmit the virus to others. The cycle threshold (Ct) is the number of amplification cycles that are needed to detect viral RNA, with higher values corresponding to lower viral loads. In August, 2020, the FDA replied to an inquiry that “it does not specify the cycle threshold ranges used to determine who is positive”, and that “commercial manufacturers and laboratories set their own.” Some laboratories defined samples with a Ct value of 40 as a positive test result.
Why did the FDA or CDC not define a national standard to set the PCR cycle threshold?
Why did diagnostic laboratories not report Ct values? Should the FDA or hospitals require that it be provided? Why did CDC guidance state that “specific Ct values should not be included in a person’s health record or used to influence a person’s individual care”?
Why were testing protocols used by different diagnostic laboratories not made available to scientists and the public?
An August 21, 2020 a review by the Center for Evidence-Based Medicine at Oxford concluded that “lower cycle threshold values may be associated with worse course of illness and outcomes and threshold values may be useful in predicting the clinical course and prognosis of patients.” Why did the CDC assert that “RT-PCR tests are used to identify and diagnose an active infection and cannot be used to show how infectious an individual person is?''
In a June 2021 report, only 3% of patient samples with Ct values >35 contained live virus. For Ct >35, the European Center for Disease Control suggested that PCR testing be repeated to minimize false positive test results and unnecessary quarantines. Why did the CDC or FDA not make such a recommendation? How many American school children, students and workers were subjected to isolation protocols despite not harboring any infectious viruses?
Different PCR thresholds should be used for different purposes. For example, for nursing home staff, false negatives are worse than false positives, so it makes sense to use a higher threshold than for asymptomatic school children. Why did the CDC not develop such purpose specific threshold recommendations?