By Hagop Kantarjian, M.D.
Nonresident Fellow in Health Policy, Baker Institute
Nadim Ajami, Ph.D.
Virologist and microbiologist
Andrew DiNardo, M.D.
Infection disease specialist
Why is early and widespread Covid-19 testing important?
Maturing experience with the Covid-19 pandemic clearly demonstrates that countries and higher-risk geographic areas (counties, cities, towns) that implemented early and wide Covid-19 testing, coupled with protective social measures (hygiene, city lockdowns, social distancing), have had significantly better control (lower infection and mortality rates, manageable hospital capacities, optimal medical management).
This blog addresses the unique and privileged health-care situation of Houston, among all cities in the world, and the particular significance of early and wide COVID-19 testing. Houston is home to the Texas Medical Center (TMC), the largest medical complex in the world. Every year, more than 10 million patients seek the expertise of the best medical specialists here. More than 106,000 employees help care for these patients. The TMC contains 56 institutions, including 21 hospitals. Over 160,000 visits are conducted daily. Health care workers have frequent contacts with patients. These medical facilities care for patients highly vulnerable to Covid-19 (diabetes; hypertension; cardiac, pulmonary and renal dysfunctions; cancer). Therefore, the spread of Covid-19 within this complex could result in a Covid-19 epicenter. The CDC criteria for testing may not be flexible enough to protect the health care workers or their patients. Infectivity is highest around days 5 to 7 from exposure, and 80% of Covid-19 spread may be caused by the 10%-25% of infected people who have minimal or no symptoms (“asymptomatic” or “pre-symptomatic”). Recovering patients (“post-symptomatic”) may also remain infectious. With impending improved Covid-19 testing capacity, including serology, monitoring guidelines and wider directed testing of health care workers are needed.
Status of the Covid-19 pandemic
The Covid-19 pandemic will continue its unrelenting spread throughout the world over the next 2-4 months, infecting millions, killing tens of thousands, weakening world economies and industries, and changing our established social norms.
As of April 10, 2020, Covid-19 has infected 1.6+ million people and caused the death of 95,000+. Depending on the extent of testing and predictive parameters, if we assume an infection rate of 5% worldwide (population 8 billion) and a mortality rate of 2%, by the end of the Covid-19 first wave, the number of infected people may exceed 400 million, and the number of deaths may be about 8 million. These figures are still very fluid.
An important concept in understanding the potential final toll of the COVID-19 pandemic is “herd immunity.” From historical data, viral spread is controlled once a percent of a population becomes immune, through either natural exposure to the virus or vaccination. It is estimated that 60% of the population should become immune to control COVID-19. With very limited testing, mostly of people with symptoms, it appears that less than 1% of the world population are infected. If true, then measures to flatten the curve will reduce the viral spread to a “slow-motion” pandemic that may reactivate when social precautions are lifted.
With wider testing, the mortality rate from Covid-19 may turn out to be lower than predicted. Currently, the mortality rates range from 2% (South Korea and Germany; very widespread testing) to 10% in Spain and 12% in Italy (delayed testing and protection measures; overwhelmed hospital infrastructures).
Improving control of the Covid-19 pandemic
There are still important unknown factors that will influence the final toll of the Covid-19 pandemic: 1) Will it recur in more than one wave (as previous viral epidemics have)? 2) Will potential later waves be more virulent (like the 1918-1920 Spanish influenza second wave) or less virulent (as are most viral infections)? 3) Can individuals develop a solid protective immunity after exposure, with the immune system producing high and sustained levels of a virus-specific neutralizing antibody (IgG) for several months? And 4) Will the virus develop mutations that will shield it from the protective effects of the antibody produced in the previous encounter?
In light of these unknowns, it is important to stress that the dire projections mentioned above are not foregone destinies. They can be modified by several important strategies. The two most important ones are still not available: safe and effective vaccines and anti-Covid-19 therapies. These will take several months, if not more, despite major scientific efforts worldwide and will help more with potential later Covid-19 waves, potentially as early as November 2020. But a second wave may be averted if there is widespread herd immunity (hence the importance of broad Covid-19 testing), and if vaccines and drugs/treatments are available by then. The two other key strategies are: 1) Continuation of strict preventive social measures. These may have to be extended for 2-6 weeks depending on the severity of spread in particular areas and the shape of the prevalence curve. 2) Widespread Covid-19 testing, contact tracing and isolation. Another important element in unprecedented catastrophes is an enlightened leadership that appreciates early on the significance of such disasters and implements a scientifically driven decision-making process. The U.S. and most of the world are still in the early-mid phases of the pandemic, during which the prevalence (total number of infected people) increases by 33% daily, which means it doubles every 3-5 days. So there is plenty of room, even though we are late in our implementation, to modify the effects of the Covid-19 pandemic.
Examples of successful Covid-19 preventions
Germany and South Korea are two countries cited for their exemplary approaches. They recognized Covid-19 early as a serious threat, developed testing methods, and started early and widespread testing, contact tracing, and quarantines. And they implemented early restrictive social measures.
On January 15, 2020, as soon as Chinese researchers released the Covid-19 genomic code to the world, experts in Charite Hospital in Berlin and elsewhere (Australia, South Korea, England) developed polymerase chain reaction (PCR) testing to detect the virus in the nasal passages, the most common source of infection spread. By the time Covid-19 started spreading in Germany (from groups infected at ski resorts in Austria and Italy), it was prepared with enough testing capacity and implemented increasingly stricter isolation measures dictated by the extent and foci of Covid-19 cases. Today, Germany conducts about 350,000 Covid-19 tests weekly (about 50,000 daily in a population of 83 million), and does not restrict testing to only those with symptoms. As of April 10, 2020, Germany (population 83 million) has reported 118,000+ infections (infection rate 0.14%) and 2,500 deaths (mortality rate 2.1%). This was also helped by the existing universal health care in Germany and its advanced medical facilities and capacities. Chancellor Angela Merkel, a research scientist by training, imposed early and increasing social distancing. She is also credited for the low mortality rate in Germany so far.
South Korea reported its first cases of Covid-19 around January 16, 2020, almost simultaneously with the U.S. Having had a previous traumatic experience with the 2015 Middle East Respiratory Syndrome (MERS), South Korea immediately implemented restrictive social measures and wide Covid-19 testing. As of April 10, 2020, South Korea (population 51 million) reported 10,400 infections (infection rate 0.02%) and 204 deaths (mortality rate 2%).
The status of Covid-19 in the U.S.
The U.S., however, did not appreciate the potential Covid-19 pandemic risk early on. Because of issues with developing Covid-19 testing by the CDC and some FDA regulatory hurdles, testing was delayed by about eight weeks. In such outbreaks, a delay of control measures by one week can triple an epidemic size and prolong it by one month. Even today, Covid-19 testing is not widely available, but instead is restricted to people meeting gradually more relaxed CDC recommended testing criteria (cough, fever, shortness of breath, exposure). Today, the U.S. conducts an average of 6,000 to 10,000 COVID -19 tests daily . As of April 10, 2020, the U.S. (population 330 million) has reported 460,000+ infections (infection rate 0.14%) and 16,500+ deaths (mortality rate 3.6%). Seattle (and New Rochelle, NY) implemented early preventive measures and appear to be showing flattening of their regional Covid-19 prevalence curves.
The first Covid-19 testing methods involved identifying the presence of the virus in the nasal passages, using swabs. The test is positive in 50% to 80% of infected individuals. False negative results may occur when the test is performed too early or too late, or because of technical issues related to sample collection, handling or testing. This test identifies patients with an active SARS-CoV-2 infection, the virus that causes Covid-19, who may also infect others. These patients, if they have mild or no symptoms, should self-quarantine for at least 2-3 weeks (until signs and symptoms resolve completely), and should be tested again to make sure the virus is no longer present. If they are moderately or severely ill, they need be hospitalized, isolated and treated. This test is widely available. The FDA has approved multiple versions. Companies like Abbott and Roche have developed kits and machines that can offer rapid, widespread testing. Abbott received FDA approval to launch a 5-15 minute test using a portable medical device (supply of 50,000 tests daily starting April 1, 2020), and approval for a larger system, m2000 Real Time quantitative PCR system, that can test up to 1 million samples a week. Still, our testing capacity lags far behind that of Germany. We should be conducting at least 1 million tests weekly (140,000+ tests daily).
Covid-19 testing in the blood involves measuring the immune response of the body to the viral exposure. The body’s first immune response to fight the infection is through production of an immunoglobulin antibody called IgM. This is akin to a first-line but poor defense system to prevent or delay the viral attack. IgM antibodies develop around 5 to 7 days from exposure and decrease 20-28 days later. By then, a second line of defense is mounted. This involves the production of IgG antibodies, which are much more effective and selective in killing the virus, and can provide long-lasting immunity. We still do not know exactly the timelines for the production and disappearance of IgM and IgG antibodies. Limited studies of coronavirus infection in Macaque monkeys, and human studies of patients recovering from Covid-19, show that infected hosts may produce IgG-based immunity that lasts several months. Detection of IgM and IgG is also referred to as serologic testing. Among immunosuppressed people with cancer, drugs that suppress (chemotherapy) or target immunoglobulins (like in multiple myeloma and chronic lymphocytic leukemia) may render these patients more susceptible to infection and poor outcomes.
Based on the Covid-19 testing in the nasal passages (PCR) and blood (serology), we can categorize people into different groups. The first group comprises those with no symptoms and who are Covid-19 negative by both nasal and blood tests. These are individuals who have not been exposed and are still at risk. Hence, the need for broad testing to understand the patterns of infectivity and herd immunity. A second group comprises those with positive PCR nasal swabs. These are infected and can infect others. They may or may not also have positive blood tests for IgM. These individuals must be isolated to avoid the viral spread. They can later be tested to demonstrate that they have negative nasal swabs and to find out if they have become immune (positive serology) (see third group). A third group comprises those who have recovered from a Covid-19 infection, and have developed IgG antibodies (positive serology). These individuals are probably resistant to a reinfection during the same wave (and perhaps a later one if they have a persistently high IgG level). They can actually protect others as buffers in crowds, and they may be able to donate plasma (rich with anti-Covid–specific IgG) to treat severely ill patients. They can also return safely to work and, if they are health care workers, they can be deployed preferentially to treat infected patients.
The above scenario, referred to as “Covid-19 immunity passports,” is not wishful thinking. It is in fact being practiced in Germany and Italy, with the aim to prevent the spread of Covid-19, protect and treat patients, reinvigorate industries and work places, and reopen and normalize societal venues.
Houston, as home to the TMC, has a unique position and responsibility. Testing here should be uniquely different from other geographies. We are medical leaders and researchers who are entrusted with the care of millions of patients. We have a responsibility to implement optimal measures that prevent the spread of Covid-19 among patients, health care workers, and their families and social communities. We do routine blood and other tests on almost all patients. During high-risk Covid-19 periods, once the Covid-19 PCR and serology tests become widely available (no obstacles related to availability of tests, machines, infrastructures, resources), it is conceivable that all patients and health care workers within the TMC would need to be tested routinely, periodically and frequently (nasal swabs for any symptoms; weekly serology?) for Covid-19. This may also become routine in all hospitals and health care facilities in the U.S. This is already partly in progress in Germany and Italy. We can do the same here.
About the authors
Hagop Kantarjian, M.D., is a medical oncologist and a nonresident in health policy fellow at the Baker Institute. His opinions do not reflect those of his institution affiliation
Nadim Ajami, Ph.D., is a virologist and microbiologist who specializes in virome and microbiome research. His opinions do not reflect those of his institution affiliation
Andrew DiNardo, M.D., is an infection disease specialist. His opinions do not reflect those of his institution affiliation.