Testing became the buzz word in solving the COVID-19 epidemic. The logic behind testing is apparent to everyone. Only the number of tests is discussed. Ashish Jha, director of the Harvard Global Health Institute thinks that 500,000 tests a day is need for the foreseeable future. The U.S. Nationwide COVID-19 testing capacity steadily increased to 145,000 tests a day. The White House unveils coronavirus testing plan to expand testing which are viewed as critical to reopening the economy.
The Michigan state COVID-19 provides Confirmed COVID-19 Cases, but it is unclear what the case means (https://www.michigan.gov/coronavirus/0,9753,7-406-98163_98173—,00.html). More than likely, the number of tested positively. This information or better disinformation only fuels scare- mongering without a real assessment of the epidemiological importance of testing. Remarkably, during the briefing in Kent county in Michigan on April 29th, the Health department refused to answer the direct question about the number of hospitalizations and death cases.
As now became the standard of the public discourse, the approaches to this specifically medical epidemiological issue are divided along the political party line with the underlining background of public fear, politician’s ignorance, and corporate business interests. The uncertainty is only how less than 365 million to test. The solution is vacillating between the test performance in the bank’s lobby or drive- through or ATM. The tendency is in implementing all three options with looming ahead options by mail or even the drone’s involvement.
On the serious note, testing issue requires professional approach cleared from todays fear and politically motivated aggregation with the focus on rational actions in the current epidemic and in the future outbreaks. There some methodology issues which should be solved.
The presented serial of posts will reflect my personal approach. Otherwise why bother to write. It is based on the infectious epidemiologist experience, familiarity with diagnostic immunology, and anatomic pathology practice. Some bias, which stems on experience collected in different time and competely different situations, is inevitable. However, the classic epidemiology rules still apply.
The diagram presents main variants of testing during COVID-19 epidemic.Molecular test is carried out by Reverse Transcription Polymerase Chain Reaction (rRT-PCR) for the qualitative detection of nucleic acid from SARS-CoV-2 in upper and lower respiratory specimens. Serum test are in determination of antibodies in plasma to SARS-CoV-2 virus.
U.S. Food and Drug Administration (FDA) has issued the first emergency use authorization (EUA) for a COVID-19 Antigen test in May. Antigen test is a “hybrid” test by the diagnostic purpose is closer to the molecular test, a sort of molecular test light. It will be discussed in a special post later.
The next posts will discuss the testing options separately. There are many details which are not discussed although they are crucial for the test’s implementation and the desired outcome.
COVID-19 testing, which gradually becomes sort of epidemiologic panacea, was discussed in the previous post, namely Epidemiological aspect of COVID-19 testing. The main conclusion from reviewed CDC documents regarding priority testing would be, in my opinion, misunderstanding of fighting major epidemic principles. CDC is following literally the infectious epidemiology orthodoxy. COVID-19 testing should have a detailed plan on the local (county) level.
While testing contacts of close to an ill person is a part of a standard infectious epidemiology procedure, COVID-19 screening is a new trend which requires detailed comprehensive evaluation. There should be a blend of detailed oriented actions with vision of the perspective in the end of epidemic, including in social and business life.
COVID-19 screening is a local epidemiology procedure. For example, in a local radio interview, Joann Hoganson, Kent county, Michigan Community Wellness Division Director brought up for screening different groups. She mentioned among other homeless, nursing homes residents though without door to door knocking.
This post presents some necessary components of a practical testing plan assuming that screening testing is necessary. Without these components the plan is not only insufficient but even contra productive. The three diagrams are the blueprint for any COVID-19 test screening local plan.
The actions after both positive and negative results of testing should be determined in detail for groups of people with certain follow up schedule.
While loosely determined critical infrastructure workers testing is questionable, health care personnel testing makes sense because their more possible encounters with the infection, better condition for obtaining the samples for reliable results and necessity of regular follow up.
The plan should specifically determine the type of the COVID-19 test. While Molecular RT-PCR test is quantitative, the Antigen nucleocapsid protein test is qualitative and more prone to false negative and even positive results. Antibody or convalescent serum test is not appropriate for screening unless it is used for serum therapy plasma collection and sentinel surveillance which is more the research realm.
The COVID-19 tests screening post is placed to draw attention to seriousness of these issue. The testing laboratories should be not only certified by Clinical Laboratory Improvement Amendments (CLIA), but an independent control of laboratories performance should be established. These issues will be discussed in the following posts. Unfortunately, the quality and reliability of the tests’ performance is taken as granted. My experience in conducting an epidemic taught me that laboratory might be sometimes a problem.
Tests screening requires a carefully developed detailed plan. Otherwise it is waste of time, resources, and source of confusion. I doubt that screening testing is necessary in the advanced stages of an epidemic. However, I do not have enough materials to confirm my opinion.
I wish I could see the detailed local (county) plan. However, it is not on the public display. Hopefully, it exists. I asked Kent county Health Department to see the plan, but nobody responded. I offered my experience, but no avail.
Although foreign experience cannot and should not be applied literally for many reasons, the Vietnam’s successes/experience is more in line with my understanding of epidemiological tactics. Without infatuations with testing, fast and aggressive quarantine at the local level is the way for fight an epidemic.
“We have a very strong system: 63 provincial CDCs (centers for disease control), more than 700 district-level CDCs, and more than 11,000 commune health centers. All of them attribute to contact tracing,” said doctor Pham with the National Institute of Hygiene and Epidemiology. https://www.msn.com/en-us/news/world/vietnam-how-this-country-of-95-million-kept-its-coronavirus-death-toll-at-zero/ar-BB14MxiR?ocid=spartandhp
This post is open ended. It reflects my vision of testing. I am going to get local materials on this subject, if they exist.
Reminiscences of my prior experience in epidemiologic practice might influence some bias to current approaches in COVID-19 epidemic.
My first job after medical school, as a doctor, was an epidemiologist position back in Russia, in Karelia near the Finland border in late 1960s. A rural place with scattered collective dairy and fur farms, lumber forest harvest factories surrounded by abounded GULAG camps. Periodic local epidemics were casual as fact of life. Dysentery, hepatitis A among people, sporadic anthrax, tularemia, foot-and -mouth disease among animals. Every epidemic had been managed from the start according infectious epidemiology rules: isolation, testing, hospitalization, local quarantine, disinfection, sanitary. In some occasions, the efforts to decrease the epidemic failed despite all standard efforts. One of the suspected culprits was the continuation of testing. When the testing was limited only to clinical necessity, the epidemic abruptly subsided. Until today, I do not have a rational explanation. Hypothetical thoughts are still lingering.
Some excerpts from basic epidemiology
Common sense and humans experience determine one of the main infectious epidemiology rules as the detection of infected to isolate from the population, as a rotten apple. Testing is an apparent solution. This post is intended to explore the testing notion as epidemiology tool to overcome the spread of COVID-19 epidemic in the USA.
Testing of patients, which require hospitalization or other clinical actions, is an apparent necessity for the differential diagnosis and effective treatment. The rest of testing is the epidemiology work routine. The diagram below presents main directions of this work. Testing with a clear plan of actions, which is following positive or negative result, only are part of them.
The importance of each component is different depending on infection, local conditions, morbidity, mortality etc. etc. In the case of COVID-19 epidemic, immediate contact testing prevails institutional contacts, while screening testing within a particular facility is incomparably more significant than the exposure testing to individuals. The latter issue requires special detailed discussion, a special post.
Below is the excerpt from PRIORITIES FOR COVID-19 TESTING section Evaluating and Testing Persons for Coronavirus Disease 2019 (COVID-19) by Center Disease Control and Prevention (CDC). Revisions were made on May 3, 2020
The entire document is pointing in the wrong direction from the epidemiology perspective. The serious objection would be on the division for High priority and Priority. The division itself and the content of the document reflect, in my view, misunderstanding by CDC strategic goals of actions in the current epidemic.
Practical epidemiology perspective
Below are my considerations regarding priorities in testing based on my prior experience as a practical infectious epidemiologist.
Hospitalized patients with symptoms are already isolated in the hospital. Their test should be done for the differential diagnosis followed by appropriate treatment.
Healthcare facility workers, workers in congregate living settings, and first responders with symptoms are already ill. Their testing is not a priority, but isolation them from contacts during their professional duties would be a priority with following testing just for clinical handling them as patients.
Residents in long-term care facilities or other congregate living settings, including prisons and shelters, with symptoms are really a high priority for separation them from the rest although this epidemiologic action would be right to do immediately even without a testing.
The testing of contacts is the necessity for localization of the source of infection. Although in a case of COVUD-19 epidemic this is a difficult task as usually in an airborne infection, an attempt would be justifiable.
“Persons without symptoms who are prioritized by health departments or clinicians, for any reason, including but not limited to: public health monitoring, sentinel surveillance, or screening of other asymptomatic individuals according to state and local plans.” These groups are a real priority for testing from the epidemiological approach, although they are in the end of the list of priorities. The main problem is that there are not local plans for such prioritizing, at least they are not in the public domain. For example, from Michigan Department of Health and Human Services
This document adds critical infrastructure workers category. The rationale is to diagnose in time infected and take them out for quarantine. When? How often? How? Etc. This document is in line with Michigan medical officials’ uninformative briefings.
Summary of epidemiological aspect of COVID-19 testing
First. Separation of the clinical and epidemiologic lines of testing should be clearly formulated in plans and actions.
Second. From the epidemiology perspective, the indication for testing of contacts includes two main groups: immediate contact with a clinically ill person and determination of individuals for testing in a contacts group. Aggressive and fast testing of infected and especially contacts in congregated living, public, and work settings is effective in the beginning of the epidemic. Screening is important in the case when the source of infection’s spread is unknown. However, screening brings mixed results when the epidemic is to some degree contained.
Third. 100 million tests per month as a maximal goal and 1 million tests per day is considered a realistic number. Unexperienced tracers, reluctant or over scared subjects of tracing, delayed or misdirected test results, and numerous other details brings only chaos. Testing become an exercise in futility. Lines of people seeking a test are also a way of potential virus shedders concentration. Most of them came for test due to the pandemic of scare, but some for a reason.
Fourth. The number of tests, as evidence of success in curtailing the epidemic, inevitably leads to relaxation of specimen’s collection, transportation, and the tests’ quality. The latter is accepted by the society as the Sun’s rise on the East. This issue will be discussed in a separate post.
The epidemiology theory orthodoxy should be adjusted to the current local conditions, economy and population attitude. My experience with epidemic on the ground suggest that the mass testing in wrong. It is a pretention of doing something with minimal positive results for an individual and maximal negative results for society: draining resources, expending the bureaucratic segment in the society, temptation of intrusion in private life under the pretense of common good, and increasing population’s anxiety. The epidemic will go by its own way determined by the rules of biology when society can correct it through diminishing the clinical damage to vulnerable people.
Everything in this epidemic is knead in sticky dough of politics. Only vaccine can compete with testing as a political issue, while the mask wearing is undisputable champion of the political divide.
Perhaps, the last. Testing infatuation already has taken a toll on the society’s mental health. Do we want to wince by our or somebody else sneeze? Do we want to measure the body temperature on permanent basis? Especially, we know how relative is this physiological parameter. Eventually the chronic fatigue syndrome will be the most frequent diagnosis.
I do not have an illusion that this post will change the course of actions during the current epidemic. Hopefully, my remarks regarding testing during an epidemic might be useful for infectious disasters in the future.
• and/or lower respiratory specimens: sputum (if produced) and/or endotracheal aspirate or bronchoalveolar lavage in patients with more severe respiratory disease.
Nasopharyngeal and oropharyngeal swabs are the commonly accepted standard. However, it is technically difficult procedure which require professional training. It is more easily present on the diagram than in a real situation (see both diagrams).
Anatomical conditions of nasopharyngeal specimen collection for COVID-19 molecular test. Red arrow- collection swab in, green arrow- swab out.
Collection a nasopharyngeal swab specimen is invasive. Following of the anatomical structure (conches), which is very much individual, require some training, skill and even instruments. Actually, this is a medical procedure. How far the swabs can reach in every collection? Are the swab’s handles calibrated for approximate depth of penetration? Many technical details can influence the test’s result.
The solution was found for the “testing, testing, testing” mantra.
“Remove preference for NP (nasopharyngeal) swabs” is among “Excerpts from CDC Summary of Recent Changes. Revisions were made on April 29, 2020 to reflect the following”.
In the list of acceptable specimens for initial diagnostic testing for SARS-CoV-2, CDC recommends:
“An anterior naris (nasal swab) specimen collected by a healthcare professional or by onsite or home self-collection (using a flocked or spun polyester swab)”.
The technical difficulty to obtain the specimen for molecular test from the most representative areas was substituted by simple nostril area. This substitution opens the gates to mass testing everywhere.
Drive-through screening centers have been designed and implemented in South Korea (Drive-Through Screening Center for COVID-19: A Safe and Efficient Screening System against Massive Community Outbreak. J Korean Med Sci. Published online Mar 16, 2020. https://doi.org/10.3346/jkms 2020 Mar 23;35(11). According to the article, this procedure increased testing capacity over 100 tests per day.
The real drive- through when a tested person opens the car’s window and a swab is poked in the nostril. You can see this procedure on the TV screen how.
The U.S. Food and Drug Administration (FDA) authorized option for the Laboratory Corporation of America (LabCorp) COVID-19 RT-PCR Test to permit testing of samples self-collected by patients at home using LabCorp’s Pixel by LabCorp COVID-19 Test home collection kit. A sample collected from the patient’s nose in saline is mailed to a LabCorp lab for testing. According to FDA Commissioner Stephen M. Hahn, M.D. 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. 30 participants (?!) were enrolled in a self-collection study by LabCorp.
This post will explore only nares specimen collection for COVID-19 RT-PCR test from the nostril’s anatomy, histology, and pathophysiology aspect leaving aside clinical, epidemiological, and medical statistic aspects and other details of this type of specimen collection. These issues require a special post.
Nostrils as part of the nasal cavity are initially a continuation of the skin lined with squamous epithelium and different size of hair. Their protective role is in preventing dust entering the respiratory tract, but it serves also of stopping infections materials, especially droplet containing airborne microorganisms. In this regard, droplet nuclei containing SARS-CoV-2 virus are “hanging” on the hair even without touching the surface of the nostril. Squamous epithelium lining of the anterior nares is followed by ciliated epithelium whose cilia form a carpet on which dust settles, as well as droplet nuclei might be engulfed by mucus. The virus, if it is there became the target of first line of immunology defense through intensive mucus production and tool of cellular (macrophages , T-lymphocyte cells). All these popular biology data are presented here just to show the place where the collection swabs is operating.
By the way, this operation is not completely innocent. During this collection manipulations, the droplet nuclei might be taken off the defense line provided by nostrils hair and pushed further into nose cavity which would not be right.
Every specimen collection has some uncertainty. Deviation of the standard bring additional confusing data. Is the method of collection reflected in the at the requisition form documents? As an extraordinary exception with the mark.
Positive SARS-CoV-2 virus molecular test is only evidence of virus presence in the nose’s content when the virus hasn’t even interacted with a person ‘s first line of innate immunity defense response.
The nares collection area for the SARS-CoV-2 virus molecular test can be done only as an extraordinary exception with the special mark. The clinical and epidemiological interpretation of the result should take into account the nares collection area.