Population Health Advisory Committee
I. Summary of T3: Testing, Tracing and Tracking
It is tempting to say we are too far behind to stop the epidemic. While we are behind in our response, we can slow it down. We know from previous outbreaks, including SARS and H1N1, as well as the 1918, 1957, and 1968 influenza pandemics that we can expect to see multiple waves. Our aim now is to minimize the second peak. The proven public health approach to COVID-19 includes three interventions to reduce exposure and new cases. The multiphase plan depends on widespread testing, extensive contact tracing and centralized isolation.
Dr. Ashish Jha, director of the Harvard Global Health Institute explains that without testing, we are blindfolded and if we’re going to get testing ramped up, local and state officials and the private sector will have to do it. The "Wakayama model" in Japan adopted strict coronavirus testing policies and managed to curb the pandemic in their community. “It's a lesson in how nimble thinking and concerted action — grounded in fast, well-targeted testing and tracing — can beat back the novel virus and break its chain of transmission.” In South Korea, health officials tested a broader sample of the population, which allowed epidemiologists to better understand the extent of the disease in the community and target the response efforts.
While there is community transmission, risk of exposure is not the same for every person in the area. The risk is greatest for persons who have/had prolonged close contact with a COVID-positive person. Considering the growing number of cases as COVID-19 circulated widely for weeks, and that we still do not have sufficient testing, it will be critical to invest in extensive contact tracing for every contact of every case to reduce transmission. Contact tracing is labor-intensive and the Center for Health Security estimates a need for 250-300 workers over the next four months for our current infection rates to be controlled in Bexar County.
Zihong Lin (pages 7-8) did an analysis of the 25,000 cases in Wuhan and concluded that stay at home orders and social distancing practices reduced the spread but not enough to stop it until they offered centralized isolation. Family transmission is common so positive people are more likely to infect others in their household and close contacts in the community when there is a mandate for everyone to stay together at home. Furthermore, the CDC estimates that as many as 25% of cases may be asymptomatic and pre-symptomatic transmission occurred between one and three days before symptom onset. The SEIR diagram, a common epidemiological model, shows how individuals move through each compartment (Susceptible-Exposed-Infectious-Recovered/Removed). Even with tighter social distancing orders, the SEIR diagram shows that there will continue to be population movement between infected people and susceptible people without smart quarantine and centralized isolation (See Diagram 1 and 2).
If we shelter in place without testing people with mild or no symptoms or without identifying likely positives through tracing, the emergency declaration will have limited impacts on suppressing this virus. Instead, we merely shift the peak. Germany’s model of testing, tracing and tracking/isolating in the early days allowed them to have a truer picture of their outbreak than places that only test symptomatic and most seriously ill or highest-risk patients.
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Diagram 1. SEIR Model for COVID-19 without a comprehensive plan
Diagram 2. SEIR Model for COVID-19 with a T3 plan
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II. Testing
There are two types of tests cleared for emergency use by the FDA:
• Molecular tests are diagnostic for acute infection. These identify the presence of specific nucleic acids produced by the virus within swabs and respiratory samples. • Serology tests look for antibodies against the coronavirus. These identify if the person has immunity.
Molecular tests SARS-Cov2 only contains RNA, which means it relies on infiltrating healthy cells to multiply and survive. A sample is collected from the nose or throat and is treated with several chemical solutions (reagents) to remove proteins and fats. In order to detect the virus, technicians need to convert the RNA to DNA so they can copy the sample (reverse transcription) hundreds of thousands of times (amplification). This produces a large enough quantity of the viral DNA to confirm the presence of SARS-Cov2. The sample mixture is then placed in an RT-PCR machine that cycles through temperatures that heat and cool the mixture to trigger specific chemical reactions. A standard real time RT-PCR setup usually goes through 35 cycles, which means it creates around 35 billion copies of the viral DNA in the sample.
With good sampling technique, RT-PCR, in general, is highly sensitive and specific and can deliver a reliable diagnosis. It continues to be the most accurate method available for detection of the coronavirus. The difference between the automated RT-PCR and a manual RT-PCR is comparable to a boxed cake mix and a cake made from scratch. The automated kits (premixed reagents mixed with the sample) have significant benefits by reducing the risk of cross-contamination and minimizing errors caused by manual interventions. The manual RT-PCR can lead to more sample-to-sample variation, less reproducibility, and less precision when mixing reagents (like a cake from scratch where you measure all the ingredients).
Many of the approved tests require nasopharyngeal (NP) swabs, which is a sample of secretions from the back of the nose and throat. The NP swab is difficult to do correctly and can be uncomfortable for the patient thus resulting in false negatives due to poor sampling technique. Given the supply issues with swabs and reagents, tests that use nasal rinses or even basic nose/throat swabs (better sampling ability) are ideal.
Serology tests The FDA granted approval for four antibody tests. A test is performed on a blood sample from the patient to detect IgM (detectable several days after infection) and IgG (detectable later after infection) that are generated as part of the human immune response to the virus. In some cases, it can take up to 11 days for an individual’s immune system to produce the antibodies. That’s why the tests are not used to diagnose patients with COVID-19 that are showing symptoms within the first two or three days. Part of the reason these antibody tests would be valuable is it can provide guidance on people potentially returning to work or continuing quarantine. IgG antibody positivity suggests the person is recovered and most likely cannot be re-infected, which would be valuable to know for healthcare workers. If the tests are ordered, healthcare and other essential workers could be prioritized. The recovered workers could be assigned COVID-19 patients. They would still use protection, but it could help stabilize the workforce by reducing exposure to the workers who haven’t been infected.
*Additional testing terms provided on page 9 and testing process and choices explained on page 10.
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III. Tracing
A case-based intervention like contact tracing is routinely used for tuberculosis, STDs, and foodborne disease but the typical timeline to prevent spread is on the order of weeks and capacity is limited to isolated outbreaks. Because COVID can be transmitted before people have symptoms, these contacts need to be identified and quarantined immediately after the case is confirmed. Even one missed case can undermine control efforts.
Contact tracing requires: • Identifying an individual who has been clinically confirmed as having COVID-19; • Identifying and listing epidemiologically meaningful contacts of that individual; • Communicating with that list of contacts to warn them of potential exposure, and linking them to public health officials, diagnostic services, or self-isolation information and services; • Monitoring symptoms of people on the contact list until diagnostic results show that a person is not infected or are beyond a reasonable time frame, such as the incubation period of the virus; and • Visualization and analytics to optimize, monitor, and determine efficacy of contact tracers. Technological solutions will be helpful across many of these use cases
With the growing number of cases and that we still do not have sufficient testing, it will be labor-intensive to control our current infection rates through identification and quarantine of exposed individuals. Based off of international experiences and current capacity, the Center for Health Security estimates Bexar County would need approximately 250-300 workers over the next four months. With secure, web-based IT support, most contact tracers should be able to work remotely via phone or other technologies to follow up on contacts and conduct interviews. The skills needed can be taught, no public health experience is necessary, and a high school education suffices. Case investigators and contact tracers receive training on the basics of disease transmission, how case isolation works and quarantine of contacts. The Association of State and Territorial Health Officials (ASTHO) created basic training modules for widespread use but the data collection protocol would need to be developed locally.
San Antonio Metropolitan Health District Tracing Timeline
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IV. Tracking (isolation)
Smart quarantine and isolation is most successful when it is offered at the time of the positive result and when it is presented to community members as voluntary, convenient, and free. Adopting a smart quarantine plan requires public planning and funding for designated temporary accommodations and staff to monitor symptoms. Most people will recover and return home in about two weeks using a time-since-recovery strategy (>6 days since onset of symptoms and 72 hours of symptom resolution) or after testing negative at least twice. The long-term benefits of a medically supervised isolation plan is that it results in fewer infections, hospitalizations, and deaths because severe cases are identified and treated earlier. Smart isolation preserves I.C.U. beds, ventilators, personal protective equipment, and healthcare workers for those who need it the most.
Local surveillance shows the close contact cases account for 41% of all positive tests (as of April 20th) and current testing criteria does not offer testing to all close contacts of all infected—there are more unascertained close contact cases in our community. San Antonio is still in the early stage and starting an intervention for centralized isolation of infected and exposed community members will reduce the number of new infections, relieve the pressure on the hospital system, stop the outbreak, and ultimately save lives.
Many cities and states have partnered and leased hotel rooms, university dormitories, shuttered school buildings, community centers, YMCAs, state parks and other commercial buildings to serve as temporary residence halls and healthcare facilities for exposed and positive community members who need accommodations to prevent the spread in their home. The accommodations are offered to mild patients who cannot care for themselves at home or who need a place to stay away from elderly or immune-compromised, for those experiencing homelessness and for healthcare workers who are worried about exposing their families. Social distancing measures are effective to limit the contact of some of the positive cases, but we cannot depend on limiting the movement of the entire population indefinitely.
Examples of other communities who have invested in isolation facilities for mild positives Linked Publication Date Location Key points Houston Chronicle 3.25 Houston Leased rooms from hotels for patients who cannot isolate at home or in a medical center Outside Online 3.20 Georgia and Louisiana Used state parks for those awaiting test results and cannot be sent home because they live with other individuals with high infection risks Daily Bulletin 3.20 Los Angeles Contracted to use 244 beds in a local hotel to quarantine patients who show symptoms but haven’t been tested Middletown Press 3.23 Connecticut Procured university for patients who do not need to be admitted to a hospital or who need a place to stay away from elderly or immune-compromised family Book Club Chicago 3.23 Chicago Partnered with five local hotels for more than 1,000 rooms available for mildly ill patients
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Exit Strategies Source Article WSJ The Journal podcast Dr. Anthony Fauci on How Life Returns to Normal New York Times How will we know when it’s time to reopen the nation? NPR CDC Director: 'Very Aggressive' Contact Tracing Needed For U.S. To Return To Normal Yahoo Coronavirus: Lockdowns are not best way to tackle COVID-19, says top WHO adviser The Nation Testing: Testing. 1-2-3 Testing. Science Mag Ending coronavirus lockdowns will be a dangerous process of trial and error New York Times Coronavirus Testing Needs to Triple Before the U.S. Can Reopen, Experts Say
Testing, Tracing, Tracking Source Article Washington Post A region in Japan launched its own coronavirus fight. It’s now called a ‘model’ in local action New York Times How South Korea flattened the curve NPR Why Testing Can Slow the Spread of the Coronavirus Washington Post Why Germany’s coronavirus death rate is so much lower than other countries’ rates Houston Chronicle Makeshift care centers, hotel rooms and quarantines: Houston gearing up for next phase of pandemic Harvard University Analysis of 25,000 Lab-Confirmed COVID-19 Cases in Wuhan
Mild Isolation Source Article Houston Chronicle Makeshift care centers, hotel rooms and quarantines: Houston gearing up for next phase of pandemic Outside Online GA and LA - State Parks Are Becoming Coronavirus Isolation Zones Daily Bulletin Sheraton Fairplex hotel will house overflow coronavirus patients Middletown Press Connecticut – details on overflow procedure at SCSU – using residence halls for housing medical staff KRPC Houston Former Kindred Hospital prepped to serve as an overflow healthcare facility for coronavirus patient The Advocate LA – considering using vacant college dorms and hotels for step-down, recovering patients Book Club Chicago Coronavirus Patients, People Who Are Homeless To Move Into Hotel Rooms During Outbreak Mercury News Coronavirus: Santa Clara County could see 2,500 to 12,000 cases by May 1 New York Times The United States Needs a ‘Smart Quarantine’
Population Health Advisory Committee
Analysis of 25,000 Lab-Confirmed COVID-19 Cases in Wuhan Xihong Lin
Message 1: Lockdown with traffic ban and home-quarantine helped but was not enough. Why? • Family transmission is common • Infected cases might infect family members and close contacts who could infect others in the community • It was challenging for infected cases to seek for medical care due to traffic ban • It was an honor system difficult to enforce. Some cases might still go out, grocery shopping, resulting in infecting others • Traffic ban, mitigation (social distancing) and home quarantine helped reduce R from 3.88 to 1.25, but was not good enough
Message #2: Centralized isolation worked! Why? • Infected patients, suspected cases and close contacts were less likely to infect others (reduce transmission) • Patients received medical care immediately • Mild cases were treated. This reduced the chance for progressing to be severe cases • Made case and close contact management and their medical care access easier • If a patient progressed to become a severe case in a mobile cabin hospital, s/he was immediately transferred to an ICU • Reduced the burden on ICU and health care system • Avoided suspected cases and close contacts from infecting family members and other community members
Message #3: A good proportion are community cases so Testing, Testing, Testing! • We estimated using the SEIR model that about 60% of infected cases were un-ascertained • They are often asymptomatic community cases who could infect others • This means increasing testing capacity for early diagnosis is critically important • Current issue in US: Low testing capacity (Need an intermediate multi- pronged strategy)
Message 4: A multi-pronged approach is needed • Large scale screening using symptoms (with/without testing kits) • Increase testing capacity • Mitigation (social distancing) and home quarantine • Centralized quarantine for confirmed and suspected cases, symptomatic cases and close contacts (asymptomatic)
Message #5: Protect the four vulnerable groups • Healthcare workers are at a much higher risk of being infected • Elderly people are at a much higher risk of being infected • Family members and close contacts of confirmed and suspected cases and close contacts are at a higher risk of being infected • Children's infection risk is much lower than adults, but the risk increased with time periods
Message #6: Early Diagnosis and Early Treatment • Early diagnosis and early treatment will help prevent cases from progressing to become severe cases who have a much higher risk of death, like patients with acute respiratory distress syndrome (ARDS) • Especially for elderly people and healthcare workers
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Additional measures for other people during the centralized isolation period in Wuhan • Continue home-quarantine and home-isolation • Continue social distancing • Provide transportation for groups 1-4 to go to hospitals or designated hotels • Control frequencies of going out, e.g., grocery shopping, for each household, and arrange grocery delivery • Healthcare workers who treat patients stay in hotels or other designated facilities to avoid them from infecting family members and communities, if they are infected • Healthcare workers in contact with cases and exposed subjects are fully protected by PPEs and included -Full gear: protective suit, medical goggle, cap, face shield, mask and gloves when seeing suspected and confirmed cases -Transmission can be through eyelashes and hair -Developed a stringent protection protocol -Trained healthcare workers how to follow the protection protocol -Suspected cases with symptoms are seen in designated clinics instead of ER or PCP offices -COVID-19 hospital level prevention and control management protocol -Patient management protocol -Cleaning and disinfection protocol
Population Health Advisory Committee
Testing Terms
Medium/Moderate Complexity Tests: These tests are more complex than waived tests and much of the testing performed in clinical laboratories falls into this category. Examples of moderate complexity tests are microscopic analysis of urinary sediment, some direct antigen strep A tests, cervical and urethral Gram stains and some hematology and chemistry tests.
High Complexity Tests: These are tests that are most difficult to perform or are most subject to error. They are usually performed only by large clinical laboratories and require quality control, quality assurance, proficiency testing and stricter personnel requirements. The major differences in requirements between moderate and high complexity testing is in quality control and personnel standards.
Nasopharyngeal swab: A method for collecting a clinical test sample of nasal secretions from the back of the nose and throat. The swab is difficult to do correctly and can be uncomfortable/painful for the patient. False negatives due to sampling technique are more common with these swabs.
Oropharyngeal (throat) swab: Sampling should be done with rigid shafted, large swabs at the back of the throat through the mouth. It’s relatively easy to do and isn’t as uncomfortable for the patient.
Nasal mid-turbinate (NMT) swab: Sampling done by inserting a swab less than one inch (about 2 cm) into nostril (until resistance is met at turbinates).
Anterior nares specimen (nasal swab, NS): Sampling done by inserting a swab at least 1 cm (0.5 inch) inside the nares and rotating the swab and leaving in place for 10 to 15 seconds. Sample both nares with same swab.
Nasal wash and nasopharyngeal wash: Sampling does not require swabs, which are in low supply.
Sensitivity: The proportion of true-positives which actually test positive and how well a test is able to detect positive individuals in a population.
Specificity: The proportion of true-negatives which actually test negative, and reflects how well an assay performs in a group of disease negative individuals.
Positive predictive value: The probability that those with a positive test truly have the disease.
Negative predictive value: The probability that those with a negative test truly don't have the disease.
DISEASE STATUS Positive Negative
Positive ++ +- Positive predictive value RESULT Negative -+ -- Negative predictive value
TEST Sensitivity Specificity
Population Health Advisory Committee
Testing Process and choices Step Choices Comments and examples 1. HC professional wearing PPE collects a Five types of specimens: 1. NP swab: Swab is difficult to do correctly and can be sample from the person's nose or throat. 1. Nasopharyngeal (NP) swab: nasal secretions from the back of the nose painful. False negatives due to sampling technique. Leaves swab in place for several seconds and throat. 2. NMT: Similar to flu swab to absorb secretions. 2. Nasal mid-turbinate (NMT) swab: use a tapered swab less than one inch 3. NS: Barely inside nose. Easy to sample. into nostril. 4. OP: Swab is relatively easy to do and is not as 3. Anterior nares specimen (NS): use a round foam swab at least 0.5 inch uncomfortable for the patient (strep test) inside the nares for 10 to 15 seconds. Sample both nares with same swab. 5. Nasal wash: Sampling does not require swabs 4. Oropharyngeal swabs (OP): use rigid, shafted, large swabs at the back of the throat through the mouth. Put both swabs in container. 5. Nasal wash and nasopharyngeal wash: Suction saline into a new sterile bulb, insert saline into one nostril with one squeeze of the bulb and release to collect recoverable nasal specimen. 2. Specimens must be labeled and Two types of tests: 1. Examples of moderate tests: complete blood count, transported to laboratory, which depends 1. Lab with CLIA certification to do moderate complexity test on automated urinalysis, urine drug screen, and automated on the test selected. clinical laboratory equipment (typically outpatient facilities have these). immunoassays. 2. Lab with CLIA certification to do high complexity test requires clinical 2. Examples of high complexity tests: cytology, laboratory expertise beyond normal automation to perform. They are peripheral smears, and most molecular diagnostic tests usually performed only by large clinical laboratories and hospitals and including RT-PCR, viral loads, etc. require quality control, quality assurance, proficiency testing and stricter personnel requirements. 3. Lab technicians combine the sample Two types of RT-PCR kits to test sample: 1. Automated RT-PCR is like a boxed cake mix. Reagents with reagents to remove proteins and fats 1. Automated RT-PCR includes premixed reagents for the sample (all-in- (cake ingredients) are provided and measured. (RT-PCR technique). The sample mixture is one) and vendor has more control on the supply chain for all the necessary 2. Manual RT-PCR is like a cake from scratch. Reagents then placed in an RT-PCR machine that chemicals. have to be acquired separately and measured. Manual cycles through temperatures that heat 2. Manual RT-PCR requires measuring reagents to mix with the sample. can lead to more sample-to-sample variation, less and cool the mixture to trigger specific Reagents are in short supply. reproducibility, and less precision when mixing reagents. chemical reactions. 4. A standard RT-PCR setup creates Three types of results: around 35 billion copies of the viral DNA. 1. Both targets detected will yield a positive result. The test is looking to detect two genetic 2. Only one target detected yields an inconclusive result. targets unique to this virus. 3. Neither targets detected yields a negative result.