Gene sequencing is enabling disease tracking in new ways that include retesting laboratory specimens from before the SARS-CoV-2 outbreak to determine when it arrived in the US
On February 26 of this year, nearly 200 executives and employees of neuroscience-biotechnology company Biogen gathered at the Boston Marriott Long Wharf hotel for their annual leadership conference. Unbeknownst to the attendees, by the end of the following day, dozens of them had been exposed to and become infected by SARS-CoV-2, the coronavirus that causes the COVID-19 illness.
Researchers now have hard evidence that attendees at this meeting returned to their communities and spread the infection. The findings of this study will be relevant to pathologists and clinical laboratory managers who are cooperating with health authorities in their communities to identify infected individuals and track the spread of the novel coronavirus.
This “superspreader” event has been closely investigated and has led to intriguing conclusions concerning the use of genetic sequencing to revealed vital information about the COVID-19 pandemic. Recent improvements in gene sequencing technology is giving scientists new ways to trace the spread of COVID-19 and other diseases, as well as a method for monitoring mutations and speeding research into various treatments and vaccines.
Genetic Sequencing Traces an Outbreak
“With genetic data, a record of our poor decisions is being captured in a whole new way,” Bronwyn MacInnis, PhD, Director of Pathogen Genomic Surveillance at the Broad Institute of MIT and Harvard, told The Washington Post (WaPo) during its analysis of the COVID-19 superspreading event. MacInnis is one of many Broad Institute, Harvard, MIT, and state of Massachusetts scientists who co-authored a study that detailed the coronavirus’ spread across Boston, including from the Biogen conference.
What they discovered is both surprising and enlightening. According to WaPo’s report, at least 35 new cases of the virus were linked directly to the Biogen conference, and the same strain was discovered in outbreaks in two homeless shelters in Boston, where 122 people were infected. The variant tracked by the Boston researchers was found in roughly 30% of the cases that have been sequenced in the state, as well as in Alaska, Senegal, and Luxembourg.
“The data reveal over 80 introductions into the Boston area, predominantly from elsewhere in the United States and Europe. We studied two superspreading events covered by the data, events that led to very different outcomes because of the timing and populations involved. One produced rapid spread in a vulnerable population but little onward transmission, while the other was a major contributor to sustained community transmission,” the researchers noted in their study abstract.
“The same two events differed significantly in the number of new mutations seen, raising the possibility that SARS-CoV-2 superspreading might encompass disparate transmission dynamics. Our results highlight the failure of measures to prevent importation into [Massachusetts] early in the outbreak, underscore the role of superspreading in amplifying an outbreak in a major urban area, and lay a foundation for contact tracing informed by genetic data,” they concluded.
The use of genetic sequencing to trace the virus could inform measures to control the spread in new ways, but currently, only about 0.33% of cases in the United States are being sequenced, MacInnis told WaPo, and that not sequencing samples is “throwing away the crown jewels of what you really want to know.”
Another role that genetic sequencing is playing in this pandemic is in tracking viral mutations. One of the ways that pandemics worsen is when viruses mutate to become deadlier or more easily spread. Scientists are using genetic sequencing to monitor SARS-CoV-2 for such mutations.
A group of scientists at Texas A&M University led by Yue Xing, PhD, published a paper titled, “MicroGMT: A Mutation Tracker for SARS-CoV-2 and Other Microbial Genome Sequences,” which explains that “Although most mutations are expected to be selectively neural, it is important to monitor if SARS-CoV-2 will eventually evolve to be a stronger or weaker infectious agent as time goes on. Therefore, it is vital to track mutations from newly sequenced SARS-CoV-2 genome.”
Korber’s findings are important because the mutation the scientists identified appears to have a fitness advantage. “Our data show that, over the course of one month, the variant carrying the D614G Spike mutation became the globally dominant form of SARS-CoV-2,” they wrote. Additionally, the study noted, people infected with the mutated variant appear to have a higher viral load in their upper respiratory tracts.
Genetic Sequencing, the Race for Treatments, Vaccines, and Managing Future Pandemics
If, as Fauci and Morens predict, future pandemics are likely, improvements in gene sequencing and analysis will become even more important for tracing, monitoring, and suppressing outbreaks. Clinical laboratory managers will want to watch this closely, as medical labs that process genetic sequencing will, no doubt, be part of that operation.
Though coronavirus infections were detected nearly simultaneously in both Canada and the US, total cases and total deaths vary dramatically leading experts to question how differences in healthcare systems might have contributed
Can clinical laboratories in the United States learn from Canada’s response to the COVID-19 pandemic? While our northern neighbor won praise for its early response to the coronavirus, since then Canada has faced criticism over a lack of access to SARS-CoV-2 testing and long wait times for test results—criticism levied at the United States’ response to the outbreak as well.
In “Canada Shows How Easy Virus Testing Can Be,” Foreign Policy reported that Canada was more prepared to mount a successful response to COVID-19 because it systematically improved its pandemic-response preparedness and testing capacity after the 2003 SARS coronavirus (SARS-CoV-1) outbreak.
“Provincial laboratories put the infrastructure in place that would allow them to run their own testing and validation without help from the federal government,” Foreign Policy wrote. “At the same time, the federally run National Microbiology Laboratory in Winnipeg expanded its own capacity to support those efforts.”
However, Canada’s pandemic response has not been criticism free. In “Health Minister Says Test Result Wait Times ‘Not Acceptable’ As Ontario Confirms 25 New COVID-19 Cases,” CBC News reported in late March about COVID-19 testing shortages and four-day wait times for test results that were “not acceptable,” particularly in Ontario, where people with mild symptoms were being refused testing and sent home unless they worked in high-risk settings.
Government Bureaucracy’s Effect on Response to COVID-19
In “Canada’s Coronavirus Response Has Not Been Perfect. But It’s Done Far Better than the US,” The Washington Post reported that the initial exposure to the virus by the US and Canada was similar. Both the US and Canada have extensive ties to Europe and China, resulting in the two countries identifying their first cases of COVID-19 within a week of one another in January. Since then, however, the progression of the disease diverged dramatically in the two nations.
To date, the US has experienced 7,361,611 total cases with 209,808 total deaths, placing it in the number one spot globally on Worldometers’ COVID-19 tracking site. By contrast, Canada is in 26th place, with 155,301 total cases and 9,278 total deaths. However, to date the US has conducted 105,401,706 total clinical laboratory tests, as opposed to Canada’s 7,220,108 total tests. This might account for the disparity in total cases, but what accounts for the huge difference in total US deaths due to COVID-19 compared to Canada?
A Fraser Institute blog post authored by Steven Globerman, PhD, Resident Scholar and Addington Chair in Measurement at the Institute and Professor Emeritus at Western Washington University, titled, “US COVID Experience Highlights Risks of Centralized Management of Healthcare,” blamed the US’ “top-down, centralized approach to testing” for the “testing fiasco” that marked the US’ initial slow response to the pandemic. Globerman maintained the Centers for Disease Control and Prevention’s insistence on producing its own COVID-19 diagnostic test, rather than using a proven German-produced test, was the first of several missteps by the US.
“While there has been much criticism of the decentralized private insurance industry in the US, the major shortcomings in testing that characterize the US experience during the current pandemic seem to be the result of the government healthcare bureaucracy,” wrote Steven Globerman, PhD, (above), Resident Scholar and Addington Chair in Measurement at the Fraser Institute and Professor Emeritus at Western Washington University. (Photo copyright: Fraser Institute.)
Globerman also noted the problems were compounded by the US government’s low initial Medicare payments to private laboratories for COVID-19 tests. “Medicare is reputed to have paid about half the price it pays for a flu test, even though the coronavirus test is substantially more expensive to produce. The price forced labs to take losses on the test, blocking many labs from scaling up production to expand the nation’s testing capacity.
“Only after major lab organizations made public pleas for increased Medicare reimbursement, and long backlogs emerged for testing and reporting test results, did Medicare agree to double its payments for coronavirus tests,” Globerman wrote.
Could National Differences in Healthcare Systems Be to Blame for Disparate COVID-19 Outcomes?
In “Canada Succeeded on Coronavirus Where America Failed. Why?” Canadian public health experts told Vox differences in the two countries’ political leadership, public health funding, and healthcare systems are to blame for the US experiencing a worse coronavirus outbreak than Canada.
Is that true? Sally C. Pipes, CEO, and Thomas W. Smith Fellow in Health Care Policy at the Pacific Research Institute, a former resident of Canada and an ardent critic of single-payer healthcare, argued that Canada’s healthcare system is plagued by long waits for elective procedures, equipment shortages, and limited access to cutting-edge drugs and therapies.
In “The Canadian Health-Care Scare,” Pipes wrote, “Our northern neighbors wait months for routine care and lack access to the latest life-saving medications and technology. Importing this system would lead to widespread misery,” adding, “Is a six-month wait for a knee replacement—the median in Canada last year—reasonable, when it keeps someone in pain and unable to work? One study puts the total cost of waiting for joint-replacement surgery after taking into account lost wages and additional tests and scans at almost $20,000. It’s no wonder that more than 323,000 Canadians left the country to seek care abroad in 2017.”
A Fraser Institute study of wait times in Canada for medically-necessary treatments underscores Pipes’ claims. According to the study, the median wait time—from general practitioner referral to treatment—across 12 medical specialties was 20.9 weeks in 2019, the second highest recorded by the Institute. If this is the case, how did Canada earn praise for its early COVID-19 response?
It’s unclear what lessons American clinical laboratories can glean from Canada’s response to COVID-19. Nevertheless, lab managers should closely watch their counterparts in other nations around the world. The coronavirus does not respect borders or care about disparities in healthcare systems.
Though not a replacement for clinical laboratory testing, the CDC says the surveillance system will help slow spread of COVID-19 in vulnerable communities
Clinical laboratory testing for COVID-19 is receiving an ally. In mid-August, the Centers for Disease Control and Prevention (CDC) and the US Department of Health and Human Services (HHS) announced they were initiating a National Wastewater Surveillance System (NWSS) in response to the COVID-19 pandemic.
In collaboration with other federal agencies, the NWSS will work with state, local, territorial, and tribal health departments to collect data on wastewater (aka, sewage) samples throughout the United States.
The goal of the NWSS is to detect SARS-CoV-2, the coronavirus that causes COVID-19, before it spreads by detecting traces of it in local sewer systems. The level of the virus detected in wastewater can be a leading indicator of a worsening outbreak in a community, according to a CDC statement.
“Quantitative SARS-CoV-2 measurements in untreated sewage can provide information on changes in total COVID-19 infection in the community contributing to that wastewater treatment plant,” noted the CDC.
People infected with the coronavirus discard traces of it—whether they are symptomatic or asymptomatic—and levels of the virus in untreated sewage can provide scientists with information about the degree of outbreak in specific areas.
The NWSS will not include or monitor homes that use septic tanks or entities with decentralized systems that treat their own waste, such as hospitals, universities, and prisons.
Not a Replacement for Clinical Laboratory Testing
The CDC stressed that sewage testing is not meant to replace clinical laboratory testing, but it can be a valuable tool in communities where COVID-19 tests are underutilized or unavailable. Wastewater testing, CDC noted in its statement, could have an enormous reach as 80% of households in the US are connected to a municipal sewage system.
The CDC is not actively taking samples from wastewater, but relying on local partners to take samples, test them, and enter data into the NWSS portal for the purpose of summarizing and interpreting for public health action.
The agency predicts that participation in a national database will ensure data comparability across separate jurisdictions.
Could Testing Raw Sewage Be More Effective than Contact Tracing for Tracking COVID-19 Outbreaks?
A Yale University study published in Nature Biotechnology, titled, “Measurement of SARS-CoV-2 RNA in Wastewater Tracks Community Infection Dynamics,” detected SARS-CoV-2 concentrations in sewage sludge in New Haven, Conn., over a 10-week period earlier this year. The results of the study “show the utility of viral RNA monitoring in municipal wastewater for SARS-CoV-2 infection surveillance at a population-wide level,” the study authors noted.
The published study states that “SARS-CoV-2 RNA was detected throughout the more than 10-week study and, when adjusted for time lags, tracked the rise and fall of cases seen in SARS-CoV-2 clinical test results and local COVID-19 hospital admissions. Relative to these indicators, SARS-CoV-2 RNA concentrations in sludge were 0–2 [days] ahead of SARS-CoV-2 positive test results by date of specimen collection, 0–2 [days] ahead of the percentage of positive tests by date of specimen collection, 1–4 [days] ahead of local hospital admissions and 6–8 [days] ahead of SARS-CoV-2 positive test results by reporting date.”
The Yale researchers concluded, “Our results demonstrate that measurement of SARS-CoV-2 RNA concentrations in primary sludge provides an approach to estimate changes in COVID-19 prevalence on a population level. Sludge results were not a leading indicator compared to positive test results or percentage of positive tests by date of specimen collection. However, they led hospitalizations by 1–4 [days] and test results by report date by ~1 week. Thus, in communities where test reporting is delayed, sludge results, if analyzed and reported on the same day as sampling, can provide substantial advance notice of infection dynamics.”
Jordan Peccia, Jr., PhD (above), Professor of Chemical and Environmental Engineering at the Yale School of Engineering and Applied Science, and study author, told NBC News, “There’s still a lot more to do. We’re one of the earlier groups to have developed a robust relationship between wastewater and coronavirus cases, but this is just a first step.” He added, “It doesn’t replace contact tracing. [But] if we know a little bit ahead of time, we can raise the alarm.” (Photo copyright: Yale University.)
Sewage Testing for COVID-19 Around the World
Sewage testing can provide data to complement other collected information about COVID-19 and steer public health decision-making. However, the CDC notes that “it is not possible to reliably and accurately predict the number of infected individuals in a community based on sewage testing” and that “more data on fecal shedding by infected individuals over the course of disease are needed to better understand the limits of detection.”
Nevertheless, some experts have leaned heavily on sewage sample testing for their conclusions about the origination of the coronavirus. In August, Dark Daily reported on a theory based on finding remnants of SARS-CoV-2 in sewage systems that suggested the virus may not have originated in Wuhan, China. Analysis of sewage samples in Italy, Spain, and Brazil indicated the virus was present in those countries before the disease was known to exist outside of China. The controversy over these findings has motivated virologists to expand wastewater testing.
The creation of the NWSS by the CDC validates growing interest in new methods of testing for infectious disease. Lower cost, faster response time, more automation of genetic sequencing, and improved analytical software has enabled this type of testing to become a useful tool. It would be wise for clinical laboratory managers to monitor the expanded use of new testing technologies for infectious diseases.
Multiple recent studies reveal a substantial number of patients continue to delay needed healthcare in the months since the onset of the SARS-CoV-2 outbreak
Based on an analysis of hospital emergency department (ED) usage, federal researchers concluded that patients continue to be cautious when visiting healthcare providers, including clinical laboratories, and that people are altering how they seek and utilize emergency care due to the COVID-19 pandemic. This not only reduces the number of typical test orders from the ER to the hospital lab, but also reduces the source of inpatient admissions.
Between March 29 and April 25 of this year, facilities the CDC examined recorded 1.2 million visits to EDs, compared to 2.1 million visits between March 31 and April 27 of last year. The steepest decrease in patient demographics was for individuals under the age of 14, women, and people living in the Northeast region.
The CDC’s data showed that 12% of ED visits were for children in pre-pandemic 2019, which dropped to 6% during the 2020 pandemic period. The CDC included ED visits from hospitals in 47 states (excluding Hawaii, South Dakota, and Wyoming) and captured information from approximately 73% of ED visits in the US.
Delaying Healthcare Visits Worsens Medical Conditions, Reduces Revenues
ED visits are an important referral source for inpatient admissions. Fewer patients in EDs means lost revenue for hospitals. However, one positive aspect of the waning number of ED visits is that it may be keeping patients with non-emergency situations away from emergency departments, thus reducing the overuse of costly ED visits. But healthcare professionals are concerned that individuals also may be avoiding or delaying care when needed, which could worsen medical situations and outcomes.
“We saw people, with COVID-19 and without, coming into the ED who were very ill,” Vik Reddy, MD, Chief Medical Officer at Wellstar Kennestone Hospital and Wellstar Windy Hill Hospital in the Atlanta area, told Modern Healthcare. He noted that some patients delayed care for critical non-COVID-19 illnesses. “The good news is that we’re seeing that trend reverse this time around. It was scary in March when we knew that people weren’t coming into the ED for heart attacks.”
The NSSP’s analysis concluded that the report’s findings were subject to at least four limitations:
The number of hospitals reporting to NSSP changes over time as facilities are added or closed. For example, 3,173 hospitals reported data in April of 2019, while 3,467 reported data in April 2020.
Diagnostic categories rely on the use of specific codes, which were missing in 20% of the ED visits reported.
NSSP coverage is not uniform across or within all the participating states.
The analysis is limited only to ED visits and does not take into account patients who did not go to an ED, but instead received treatment in other healthcare environments, such as urgent care clinics.
The graphics above are taken from a Washington Post article which reported that the newspaper’s analysis of smartphone location data of hospital traffic in 2020 showed the “drop” in hospital usage had turned into “a crash,” compared to the same two months last year, and that, “As in many other industries, those lost visits represented a widespread financial crisis for hospitals and other healthcare providers, even in places the novel coronavirus hardly touched.” (Graphics copyright: The Washington Post.)
Additional Studies Show Patients Avoiding Hospital EDs, Delaying Care
Other sources also are reporting similar findings regarding consumer attitudes towards seeking medical care during the COVID-19 pandemic. A PricewaterhouseCoopers survey released in May found that about 45% of 2,500 consumers surveyed plan to forgo their annual physical in 2020, due to the pandemic, Modern Healthcare reported.
In addition, an Optum Consumer Pulse Survey released in May found that nearly 20% of 700 surveyed individuals stated they were likely to avoid hospital EDs even if they were showing signs of a heart attack or appendicitis. Another 40% stated they were likely to avoid the ED if they had a cut that required stitches.
In “Americans Are Delaying Medical Care, and It’s Devastating Health-Care Providers,” The Washington Post analyzed hospital use during the pandemic based on smartphone tracking data. WaPo’s report found a significant drop in patients seeking in-person healthcare with many areas across the country reporting a 50% reduction in patients when compared to last year.
The article also states that almost 94 million people have delayed medical care due to the COVID-19 pandemic, and that 66 million of those individuals needed medical care unrelated to the virus but did not receive it.
These studies and others are showing a pattern. The COVID-19 pandemic has changed when and where patients access healthcare, and if the trend continues, it could have a long-term impact on clinical laboratories. Since fewer people are seeking medical care, fewer laboratory tests are being ordered and performed, which means less work and revenue for the nations’ hospital and independent clinical labs.
If the proposed rule becomes final, it may shift some inpatient medical laboratory testing away from hospital labs and to independent clinical laboratories
Medical laboratories in hospitals and health systems already feel the pinch of less test orders originating from their own emergency departments (ED). Now, more tests associated with inpatient care might also shift away from hospital labs due to a new proposed rule from the federal Centers for Medicaid and Medicare Services (CMS) that would move 1,740 specific procedures from inpatient care settings to outpatient ambulatory surgical centers (ACS).
Further, the proposed rule would completely phase out the “inpatient only” (IPO) list of services over a three-year transitional period, with total elimination of the IPO list by Calendar Year (CY) 2024.
If finalized as written, the rule (CMS-1736-P) would have a negative impact on the finances of hospitals laboratories as more patients get their care in outpatient settings instead of their local hospitals.
Conversely, hospital outreach labs that service ambulatory surgical centers and other outpatient settings could have an opportunity to pick up more medical laboratory test referrals.
The proposed rule, titled, “Medicare Program: Hospital Outpatient Prospective Payment and Ambulatory Surgical Center Payment Systems and Quality Reporting Programs; New Categories for Hospital Outpatient Department Prior Authorization Process; Clinical Laboratory Fee Schedule: Laboratory Date of Service Policy; Overall Hospital Quality Star Rating Methodology; and Physician-Owned Hospitals,” was published in the Federal Register on August 12, 2020, and is open for comments until 10/05/2020.
“In this proposed rule, we describe the proposed changes to the amounts and factors used to determine the payment rates for Medicare services paid under the OPPS and those paid under the ASC payment system.
Moving from Highest Cost Settings to Lower Cost Settings
In the big picture, these changes can save Medicare money. By shifting procedures for Medicare patients from the highest cost settings—hospital inpatient—to lower cost settings, such as outpatient ambulatory surgical centers, and by eliminating the inpatient-only list, physicians have more leeway to determine for themselves whether a patient needs to be hospitalized for any given procedure.
In “Do Hospitals Have a Target on their Back?” healthcare coding and reimbursement consultant, Terry Fletcher, an editorial board member with ICD10monitor, wrote, “Last year, CMS proposed removing certain services from the inpatient-only list and making them available on an outpatient basis, which it said would help lower costs.
“According to the proposal, ambulatory surgical centers would get a payment increase of 2.6%, and CMS estimated total payments to them for 2021 will be about $5.45 billion, an increase of $160 million from this year,” she added.
Fewer Referrals for Inpatient Lab, More for Hospital Outreach Labs
The impact of the proposed rule is predictable—price shopping will ensue, which is what Medicare wants. Thus, with the removal of the inpatient-only procedure list, the clinical laboratories of hospitals and health systems will likely see a reduction in inpatient test orders. But clinical laboratories participating in hospital outreach programs may see an increase in test orders, as doctors transition to more outpatient procedures.
This seemingly simple shift may be more complicated than it appears, however, for both patients and labs. “In general, any routine test is going to be more expensive at a hospital,” Jean Pinder, founder and CEO of ClearHealthCosts, told Cleveland.com.
There may be other concerns as well. Convenience, insurance coverage, and physician recommendations often influence patient decisions about clinical laboratories.
The chart above, taken from the article by Cleveland.com, “compares prices for common clinical laboratory and imaging tests charged by an independent lab and local hospitals. These are charges that a person would pay without insurance reimbursements. Some University Hospitals prices in the chart differ from those on its website because some prices reflect inpatient, hospital-based services. Many factors can affect [a patient’s] final out-of-pocket costs, including health insurance coverage and individual aspects of your medical treatment.” (Graphic and caption copyright: Cleveland.com.)
Change Is the Only Constant
The entire healthcare industry is undergoing change that is unlikely to end any time soon. Clinical laboratory managers who stay aware of trends in the industry and remain informed on regulatory changes, and who look for opportunities as the business landscape evolves, will have the best chance for guiding their labs to success.
That would certainly be true if CMS is able to publish a final rule that shifts a large number of procedures away from inpatient care and categorizes them as outpatient procedures.
Might clinical laboratories soon be called on to conduct mass testing to find people who show little or no symptoms even though they are infected with the coronavirus?
Clinical laboratory managers understand that as demand for COVID-19 testing exceeds supplies, what testing is done is generally performed on symptomatic patients. And yet, it is the asymptomatic individuals—those who are shown to be infected with the SARS-CoV-2 coronavirus, but who experience no symptoms of the illness—who may hold the key to creating effective treatments and vaccinations.
So, as the COVID-19 pandemic persists, scientists are asking why some people who are infected remain asymptomatic, while others die. Why do some patients get severely ill and others do not? Researchers at the University of California San Francisco (UCSF) and Stanford University School of Medicine (Stanford Medicine) are attempting to answer these questions as they investigate viral transmission, masking, immunity, and more.
And pressure is increasing on researchers to find the answer. According to Monica Gandhi, MD, MPH, an infectious disease specialist and Professor of Medicine at UCSF, millions of people may be asymptomatic and unknowingly spreading the virus. Gandhi is also Associate Division Chief (Clinical Operations/Education) of the Division of HIV, Infectious Diseases, and Global Medicine at UCSF’s Zuckerberg San Francisco General Hospital and Trauma Center.
“If we did a mass testing campaign on 300 million Americans right now, I think the rate of asymptomatic infection would be somewhere between 50% and 80% of cases,” she told UCSF Magazine.
On a smaller scale, her statement was borne out. In a study conducted in San Francisco’s Mission District during the first six weeks of the city’s shelter-in-place order, UCSF researchers conducted SARS-CoV-2 reverse transcription-PCR and antibody (Abbott ARCHITECT IgG) testing on 3,000 people. Approximately 53% tested positive for COVID-19 but had no symptoms such as fever, cough, and muscle aches, according to data reported by Carina Marquez, MD, UCSF Assistant Professor of Medicine and co-author of the study, in The Mercury News.
Pandemic Control’s Biggest Challenge: Asymptomatic People
In an editorial in the New England Journal of Medicine (NEJM), Gandhi wrote that transmission of the virus by asymptomatic people is the “Achilles heel of COVID-19 pandemic control.”
In her article, Gandhi compared SARS-CoV-2, the coronavirus that causes COVID-19, to SARS-CoV-1, the coronavirus that caused the 2003 SARS epidemic. One difference lies in how the virus sheds. In the case of SARS-CoV-2, that takes place in the upper respiratory tract, but with SARS-CoV-1, it takes place in the lower tract. In the latter, symptoms are more likely to be detected, Gandhi explained. Thus, asymptomatic carriers of the coronavirus may go undetected.
“Viral loads with SARS-CoV-1, which are associated with symptom onset, peak a median of five days later than viral loads with SARS-CoV-2, which makes symptom-based detection of infection more effective in the case of SARS-CoV-1,” Gandhi wrote. “With influenza, persons with asymptomatic disease generally have lower quantitative viral loads in secretions from the upper respiratory tract than from the lower respiratory tract and a shorter duration of viral shedding than persons with symptoms, which decreases the risk of transmission from paucisymptomatic persons.”
Rick Wright (above), an insurance broker in Redwood City, Calif., was infected with the COVID-19 coronavirus while aboard a Diamond Princess Cruise. He underwent 40 days of isolation, and though he consistently tested positive for the coronavirus, he experienced no symptoms of the illness. “I never felt sick. Not a cough, wheezing, headache. Absolutely nothing,” he told Mercury News. (Photo copyright: The Mercury News.)
Stanford Studies Immune Responses in COVID-19 Patients
Meanwhile, scientists at the Stanford University School of Medicine were on their own quest to find out why COVID-19 causes severe disease in some people and mild symptoms in others.
“One of the great mysteries of COVID-19 infections has been that some people develop severe disease, while others seem to recover quickly. Now, we have some insight into why that happens,” Bali Pulendran, PhD, Stanford Professor of Pathology, Microbiology, and Immunology and Senior Author of the study in a Stanford Medicine news release.
The Stanford research suggested that three molecules—EN-RAGE, TNFSF14, and oncostatin-M—“correlated with disease and increased bacterial products in human plasma” of COVID-19 patients.
“Our multiplex analysis of plasma cytokines revealed enhanced levels of several proinflammatory cytokines and a strong association of the inflammatory mediators EN-RAGE, TNFSF14, and OSM with clinical severity of the disease,” the scientists wrote in Science.
Pulendran hypothesized that the molecules originated in patients’ lungs, which was the infection site.
“These findings reveal how the immune system goes awry during coronavirus infections, leading to severe disease and point to potential therapeutic targets,” Pulendran said in the news release, adding, “These three molecules and their receptors could represent attractive therapeutic targets in combating COVID-19.”
Clinical Laboratories May Do More Testing of Asymptomatic People
The research continues. In a televised news conference, President Trump said COVID-19 testing plays an important role in “preventing transmission of the virus.” Clearly this is true and learning why some people who are infected experience little or no symptoms may be key to defeating COVID-19.
Thus, as the nation reopens, clinical laboratories may want to find ways to offer COVID-19 testing beyond hospitalized symptomatic patients and people who show up at independent labs with doctors’ orders. As supplies permit, laboratory managers may want to partner with providers in their communities to identify people who are asymptomatic and appear to be well, but who may be transmitting the coronavirus.
