People who think theyve been exposed to the novel coronavirus are clamoring for antibody tests blood screens that can detect who has previously been infected and, the hope is, signal who is protected from another case of Covid-19.
But as the tests roll out, some experts are trying to inject a bit of restraint into the excitement that the results of these tests could, for example, clear people to get back to work. Some antibody tests have not been validated, they warn. Even those that have been can still provide false results. And an accurate positive test may be hard to interpret: the virus is so new that researchers cannot say for sure what sort of results will signal immunity or how long that armor will last.
They caution that policymakers may be making sweeping economic and social decisions plans to reopen businesses or schools, for example based on limited data, assumptions, and whats known about other viruses. President Trump last week unveiled a three-phased approach to reopen the country; he said some states that have seen declining case counts could start easing social distancing requirements immediately. And some authorities have raised the idea of granting immunity passports to people who recover from the virus to allow them to return to daily life without restrictions.
advertisement
Before we embark on huge policy decisions, like issuing immunity certificates to get people back to work, I think its good that people are saying, Hold up, we dont know that much about immunity to this virus, said Angela Rasmussen, a Columbia University virologist.
To be clear, most experts do think an initial infection from the coronavirus, called SARS-CoV-2, will grant people immunity to the virus for some amount of time. That is generally the case with acute infections from other viruses, including other coronaviruses.
advertisement
With data limited, sometimes you have to act on a historical basis, Anthony Fauci, the head of the National Institute of Allergy and Infectious Diseases, said in a webcast with JAMA this month. Its a reasonable assumption that this virus is not changing very much. If we get infected now and it comes back next February or March we think this person is going to be protected.
Still, the World Health Organization has stressed that the presumed immunity can only be proven as scientists study those who have recovered for longer periods. The agency is working on guidance for interpreting the results of antibody tests, also called serologic tests.
Right now, we have no evidence that the use of a serologic test can show that an individual is immune or is protected from reinfection, the WHOs Maria Van Kerkhove said at a briefing last week.
Below, STAT looks at the looming questions about antibodies and immunity that scientists are racing to answer.
What are antibody tests? How widely available are they? And how accurate?
The tests look for antibodies in the blood. Because antibodies are unique to a particular pathogen, their presence is proof the person was infected by the coronavirus and mounted an immune response. The hope is that the presence of the antibodies is an indication that the person is protected from another infection.
These are different from the tests used to diagnose active infections, which look for pieces of the virus genome.
Commercial antibody tests are starting to appear on the market, but so far, the Food and Drug Administration has only cleared a few through Emergency Use Authorizations. And already, health regulators are warning that the ones on the market may vary in their accuracy.
I am concerned that some of the antibody tests that are on the market that havent gone through FDA scientific review may not be as accurate as wed like them to be, FDA Commissioner Stephen Hahn said on Meet the Press earlier this month. He added that no test is 100% accurate, but what we dont want are wildly inaccurate tests.
Even the best tests will generate some false positives (identifying antibodies that dont actually exist) and some false negatives (missing antibodies that really are there). Countries including the U.K. have run into accuracy issues with antibody tests, slowing down their efforts for widespread surveys.
The fear in this case with imprecise tests is that false positives could errantly lead people to think theyre protected from the virus when they have yet to have an initial infection.
Serology testing isnt a panacea, said Scott Becker, the CEO of the Association of Public Health Laboratories. When its used, we need to ensure there are good quality tests used.
One specific concern with antibody tests for SARS-CoV-2: they might pick up antibodies to other types of coronaviruses.
Globally, there have only been a few thousand people exposed to the other coronaviruses that have caused outbreak emergencies, SARS and MERS. But there are four other coronaviruses that circulate in people and cause roughly a quarter of all common colds. Its thought that just about everyone has antibodies to some combination of those coronaviruses, so serological tests for SARS-CoV-2 would need to be able to differentiate among them.
What can be gleaned from serological results?
Detecting antibodies is the first step. Interpreting what they mean is harder.
Typically, a virus that causes an acute infection will prompt the bodys immune system to start churning out specific antibodies. Even after the virus is cleared, these neutralizing antibodies float around, ready to rally a response should that virus try to infect again. The virus might infect a few cells, but it cant really gain a toehold before the immune system banishes it. (This is not the case for viruses that cause chronic infections, like HIV and, in many cases, hepatitis C.)
The infection is basically stopped in its tracks before it can go anywhere, said Stephen Goldstein, a University of Utah virologist. But, Goldstein added, the durability of that protection varies depending on the virus.
Scientists who have looked at antibodies to other coronaviruses both the common-cold causing foursome and SARS and MERS found they persisted for at least a few years, indicating people were protected from reinfection for at least that long. From then, protection might start to wane, not drop off completely.
The experience with other viruses, including the other coronaviruses, has encouraged what Harvard epidemiologist Marc Lipsitch summed up as the educated guess in a recent column in the New York Times: After being infected with SARS-CoV-2, most individuals will have an immune response, some better than others. That response, it may be assumed, will offer some protection over the medium term at least a year and then its effectiveness might decline.
But many serological tests arent like pregnancy tests, with a yes or no result. They will reveal the levels (or titer) of antibodies in a persons blood. And thats where things can get a bit trickier. At this point, scientists cant say for sure what level of antibodies might be required for a person to be protected from a second Covid-19 case. They also cant say how long people are safeguarded, though its thought that a higher initial titer will take longer to wane than low levels.
Further investigation is needed to understand the duration of protective immunity for SARS-CoV-2, a committee from the National Academies of Sciences, Engineering, and Medicine wrote in a report this month.
Its not just whether someone is immune themselves. The next assumption is that people who have antibodies cannot spread the virus to others. Again, that hasnt been shown yet.
We dont have nearly the immunological or biological data at this point to say that if someone has a strong enough immune response that they are protected from symptoms, that they cannot be transmitters, said Michael Mina, an epidemiologist at Harvards T.H. Chan School of Public Health.
The challenge, as the National Academies report highlighted, is that no one knew about this virus until a few months ago. That means they havent been able to study what happens to people who recover from Covid-19 and if and how long they are protected for more than a short period of time.
One key uncertainty arises from the fact that we are early in this outbreak and survivors from the first weeks of infection in China are, at most, only three months since recovery, the report said.
What else can antibody tests show?
In addition to identifying those who have been infected, antibody tests can also suggest at a broader level how widely the virus has spread. These data have implications for how severe future outbreaks of cases might be and what kind of restrictions communities might need to live under. If more people have been infected than known a strong likelihood, given the number of mild infections that might have been missed and testing limitations in countries including the United States then more people are thought to be protected going forward.
In the United States, the Centers for Disease Control and Prevention and the National Institutes of Health have both launched serosurveys to assess how many people might have contracted the virus. Even employees of Major League Baseball teams have been enlisted in a study enrolling thousands of patients.
What have data from serosurveys shown thus far about antibody generation?
A number of countries have launched large serosurveys, so hopefully well have a better sense soon of the levels of antibodies being generated by individuals who recover from Covid-19 and among the general population. For now, though, there have only been limited data released from a couple small studies.
Scientists in Europe have pointed to strong antibody production in patients within a few weeks of infection. One study found that people were generally quick to form antibodies, which could help explain why the majority of people do not develop severe cases of Covid-19.
But one preprint released this month complicated the landscape. (Preprints have not been peer-reviewed or published yet in a research journal.) Researchers in Shanghai reported that of 175 patients with confirmed Covid-19, about a third had low antibody levels and some had no detectable antibodies. The findings suggest that the strength of the antibody response could correlate to the severity of infection, though thats not known for sure. They also raised concerns that those with a weaker antibody response might not be immune from reinfection.
But outside researchers have said that conclusions about immunity cant be drawn from what the study found. For one, there are different kinds of antibodies, so some might exist that the test wasnt looking for. Secondly, studies in other coronaviruses have shown that antibody responses vary from person to person, without clear implications for how protected someone is from another infection.
And, researchers say, antibodies are not the only trick the body has to protect itself. Immune cells also form memories after an initial infection and can be rallied quickly should that same pathogen try to strike again, even without antibodies or after antibody levels fade.
People that lose that serum neutralization it doesnt mean necessarily that theyre not going to have some level of immunity, said virologist Vineet Menachery of the University of Texas Medical Branch. Your immune system hasnt forgotten. It may just take them a couple of days to generate that immune response and be able to clear a virus.
He added that its likely that if and when protection starts to wane and people contract the coronavirus a second time, its likely to cause an even milder illness.
Ive heard reports of reinfection or reactivated virus. Whats going on there?
Health officials in some countries have said theyve seen examples of people recovering from Covid-19 only to test positive for the virus again what theyve taken to calling reactivation, to differentiate it from a second infection.
But experts are skeptical that either is occurring.
While no possibility can be eliminated at this early stage of the outbreak, they say that there are more likely explanations for a positive diagnostic test coming after a negative test.
For one: The tests used to diagnose Covid-19 look for snippets of the virus genome, its RNA. But what they cant tell you is if what theyre finding is evidence of live virus, meaning infectious virus. Once a person fights off a virus, viral particles tend to linger for some time. These cannot cause infections, but they can trigger a positive test. The levels of these particles can fluctuate, which explains how a test could come back positive after a negative test. But it does not mean the virus has become active, or infectious, again.
And two: the diagnostic tests typically rely on patient samples pulled from way back in their nasal passages. Collecting that specimen is not foolproof. Testing a sample that was improperly collected could lead to a negative test even if the person has the virus. If that patient then gets another test, it might accurately show they have the virus.
As Jana Broadhurst, the director of the Nebraska Biocontainment Units clinical laboratory, said, garbage in, garbage out.
Sharon Begley contributed reporting.
See more here:
Everything we know about coronavirus immunity, and plenty we still don't - STAT
- Technion team discovers important adaptive strategy of the microbiome, impacting immune system - The Jerusalem Post - April 16th, 2024
- Targeting aging and age-related diseases with vaccines - Nature.com - April 16th, 2024
- Single cell analysis unveils B cell-dominated immune subtypes in HNSCC for enhanced prognostic and therapeutic ... - Nature.com - April 16th, 2024
- After the Smoke Clears: Scars on the Immune System - The Scientist - April 16th, 2024
- Exercise and the Immune System: What's the Latest Research? - Technology Networks - April 16th, 2024
- Analysis of immune cell infiltration characteristics in severe acute pancreatitis through integrated bioinformatics ... - Nature.com - April 16th, 2024
- Vaccination impairs de novo immune response to omicron breakthrough infection, a precondition for the original ... - Nature.com - April 16th, 2024
- Harnessing the power of the body's own cells to defeat cancer - Press Publications Inc. - April 16th, 2024
- Best Life: Immunotherapy targets brain cancer - Action News 5 - April 16th, 2024
- Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review | Cell Death ... - Nature.com - April 16th, 2024
- New insights on B cells: Researchers explore building better antibodies and curbing autoimmune diseases - Medical Xpress - April 16th, 2024
- Immune cells' intense reaction to the coronavirus may lead to pneumonia - Science News Magazine - April 16th, 2024
- The telltale traces long Covid leaves in the blood - healthcare-in-europe.com - April 16th, 2024
- Overview of the Immune System - The Merck Manuals - March 18th, 2024
- SUNDAY Unraveling The Gut-Brain Connection: How Infant Gut Bacteria Shape Immune Resilience | TheHealthSit - TheHealthSite - March 18th, 2024
- Making drugs from T cells: The quantitative pharmacology of engineered T cell therapeutics | npj Systems Biology and ... - Nature.com - March 18th, 2024
- Study unlocks the mystery of neonatal neutropenia in newborns - News-Medical.Net - March 18th, 2024
- Vertebral Subluxation and Systems Biology: An Integrative Review Exploring the Salutogenic Influence of Chiropractic ... - Cureus - March 18th, 2024
- A new strategy to attack aggressive brain cancer shrank tumors in two early tests - ABC News - March 18th, 2024
- Turning on the Bat Signal - The Scientist - March 18th, 2024
- Power Foods That Can Support Your Immune System - Videos from The Weather Channel - The Weather Channel - March 18th, 2024
- Report: Aggressive brain tumors respond to new, immune-focused therapy - UPI News - March 18th, 2024
- Designer immune-cell therapy could shrink deadly brain tumors, early trials show - Livescience.com - March 18th, 2024
- 20.2: Introduction to the Immune System - Biology LibreTexts - February 27th, 2024
- Can one shot of yoghurt really boost your immunity and gut health? - Daily Mail - February 27th, 2024
- New cancer therapy approved by FDA supercharges bodys immune system - The Washington Post - February 27th, 2024
- How bubonic plague rewired the human immune system - BBC.com - February 27th, 2024
- Innovative therapy targets and destroys leukemia stem cells - News-Medical.Net - February 27th, 2024
- Participate in Our Study for $100; Open Slots This Week - University of Arkansas Newswire - February 27th, 2024
- Sexual dimorphism during integrative endocrine and immune responses to ionizing radiation in mice | Scientific Reports - Nature.com - February 27th, 2024
- Comprehensive pan-cancer analysis identifies the RNA-binding protein LRPPRC as a novel prognostic and immune ... - ScienceDirect.com - February 27th, 2024
- YOUR HEALTH: The HAMR fights cancer - WAFB - February 27th, 2024
- Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat - News-Medical.Net - February 27th, 2024
- How the powerhouse of the cell could be cancers Achilles heel - Freethink - February 27th, 2024
- Food is medicine: The science behind zinc and other supplements for immune health - Healio - February 27th, 2024
- Unleashing Our Immune Response to Quash Cancer - Medscape - February 27th, 2024
- Tumor histoculture captures the dynamic interactions between tumor and immune components in response to anti-PD1 ... - Nature.com - February 27th, 2024
- Converging and evolving immuno-genomic routes toward immune escape in breast cancer - Nature.com - February 27th, 2024
- Sanjula Jain Urges a Comprehensive Approach in Address Alarming Rise in Cancer Cases Among Younger Populations - Managed Healthcare Executive - February 27th, 2024
- Cystic fibrosis breakthrough points to zinc as infection buster - New Atlas - February 27th, 2024
- Exploring synergies between B- and T-cell vaccine approaches to optimize immune responses against HIVworkshop ... - Nature.com - February 27th, 2024
- Is the 100-year old TB vaccine a new weapon against Alzheimers? - The Guardian - February 27th, 2024
- Immune system in the blood of Alzheimer's patients found to be epigenetically altered - News-Medical.Net - February 10th, 2024
- What impact does exercise have on your immune system? And how to stay well while cycling - BikeRadar - February 10th, 2024
- Had COVID recently? Here's what to know about how long immunity lasts, long COVID, and more - AAMC - February 10th, 2024
- Noor Momin harnesses the immune system to treat heart disease | Penn Today - Penn Today - February 10th, 2024
- Research reveals a process tumors use to induce immune suppressor cells and evade immunotherapy - Medical Xpress - February 10th, 2024
- Immune targeting of HIV-1 reservoir cells: a path to elimination strategies and cure - Nature.com - February 10th, 2024
- Preventing severe allergic reactions with nanoparticles - National Institutes of Health (NIH) (.gov) - February 10th, 2024
- Sugary handshakes are how cells talk to each other understanding these name tags can clarify how the immune ... - The Conversation Indonesia - February 10th, 2024
- Scientists have identified an immune cell that can cause allergies - EL PAS USA - February 10th, 2024
- Sickle cell and the importance of the immune system - Punch Newspapers - February 10th, 2024
- Which cancers can be treated with immune checkpoint inhibitors? - MD Anderson Cancer Center - February 10th, 2024
- How does waste leave the brain? Washington University School of Medicine in St. Louis - Washington University School of Medicine in St. Louis - February 10th, 2024
- Healthy Kids: Give your immune system a boost to stay healthy this winter - nbc16.com - February 10th, 2024
- The impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode ... - Cardiovascular Diabetology - February 10th, 2024
- Impact of Chronic Stress on Immune System and Depression | Health News - Medriva - February 10th, 2024
- I tried 'swamp soup,' the viral recipe that promises to boost your immune system - Yahoo News - February 10th, 2024
- Understanding Immune Checkpoint Inhibition Therapy: Challenges and Strategies - Medriva - February 10th, 2024
- One Simple Change May Dramatically Boost The Effect of COVID-19 Vaccines - ScienceAlert - February 10th, 2024
- The gut virome is associated with stress-induced changes in behaviour and immune responses in mice - Nature.com - February 10th, 2024
- Cancer vaccines are in the works to fight BRCA-linked gene mutations - The Philadelphia Inquirer - February 10th, 2024
- What are the organs of the immune system? - InformedHealth.org - NCBI ... - January 17th, 2024
- Novel insights into the immune response to bacterial T cell superantigens - Nature.com - January 17th, 2024
- FDA signs off on Takeda's HyQvia as maintenance therapy for CIDP - FiercePharma - January 17th, 2024
- CBDs Pobezinsky and Pobezinskaya Use Flow Cytometry to Determine How Tumor Cells Outwit the Bodys Immune ... - UMass News and Media Relations - January 17th, 2024
- Boosting. What To Do. - Science Based Medicine - January 17th, 2024
- Axelia Oncology takes its TLR2/6 agonist into the clinic to harness the innate immune system - BioWorld Online - January 17th, 2024
- Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to ... - Nature.com - January 17th, 2024
- Opinion | Thanks to mRNA, Future Drugs Will Be Easier and Faster to Make - Mississippi Free Press - January 17th, 2024
- Elon research team models the COVID immune response, one equation at a time - Today at Elon - January 17th, 2024
- Are plant-based meals good for your immune system? 4 things to know about improving your health this week. - Yahoo Life - January 17th, 2024
- Scientists Find Key To Potential Breast Cancer Prevention, Treatment | Newsroom - UNC Health and UNC School of Medicine - January 17th, 2024
- What if every germ hit you at the exact same time? An immunologist explains - The Conversation - January 17th, 2024
- Why Don't We Have a Staph Vaccine? - Healthnews.com - January 17th, 2024
- Best ways to improve your immune system - The Business Standard - January 17th, 2024
- Stanford University researchers think future pandemics could be prevented with universal vaccines - KGO-TV - January 17th, 2024
- Why you may feel depressed and anxious when you're ill and how to cope with it - The Conversation - January 17th, 2024
- New mechanism with potential to boost checkpoint-blocking cancer immunotherapies identified - Medical Xpress - January 17th, 2024
- Battling Bugs and Blues: The Interplay of Infection and Emotion - News-Medical.Net - January 17th, 2024