Saturday, April 25, 2020

WHO Scientific Brief: `Immunity Passports' For COVID-19



One of the more tantalizing `solutions' for reopening the economy, and getting life back to something akin to `normal', is using antibody tests to determine who has already been exposed to the virus, and is presumably immune to re-infection.
The idea is that these immune individuals would be given `passports' to allow them to work, donate blood (for convalescent plasma and for the general blood supply), and perhaps even socialize with others who have been similarly `cleared'. 
Putting aside some of the obvious societal, economic, and enforcement issues this `immunological caste system' might cause, for this to work you'd have to A) have tens of millions of highly accurate antibody tests   B) be certain that post-infection antibodies convey immunity, and C) know how long that protection lasts. 
And right now, we don't have good answers for any of these questions. 
Despite the rolling out of scores of antibody tests by various labs over the past couple of weeks, most have not been verified or approved by the FDA.  We've seen disturbing reports of less-than-reliable antibody tests for COVID-19 being sold, both in the United States, and around the world (see New Test Hopes Dashed as U.K. Finds Antibody Kits Don’t Deliver). 
It is also worth noting, that after more than 7 years of research, as of last October no fully validated antibody test had been developed for MERS-CoV (see EID Journal: Sensitivity and Specificity Of MERS-CoV Antibody Testing). 
Two days ago, the IDSA (Infectious Diseases Society of America) issued the following statement on serological test accuracy and usefulness.
IDSA COVID-19 Antibody Testing Primer
Updated: April 22, 2020
As serological testing for SARS-CoV-2 advances, there are multiple issues that need to be addressed, from test quality to interpretation. Unlike molecular tests for COVID-19 (e.g., PCR), antibody tests may be better suited for public health surveillance and vaccine development than for diagnosis.
The current antibody testing landscape is varied and clinically unverified, and these tests should not be used as the sole test for diagnostic decisions. Further, until more evidence about protective immunity is available, serology results should not be used to make staffing decisions or decisions regarding the need for personal protective equipment.  
Even assuming an antibody test with near 100% sensitivity and specificity can be developed, manufactured, and distributed at a scale large enough to make sense, we still don't know how protective (or at what levels) post-infection antibodies are against reinfection.
These are issues we've discussed previously (see COVID-19: From Here To Immunity and When Studies Collide (COVID-19 Edition)).
Two weeks ago, epidemiologist Dr. Marc Lipsitch published an opinion piece in the New York Times that went over the still slim and sometimes conflicting evidence for acquired immunity from COVID-19 infection, along with some of the challenges of creating a vaccine (see Who Is Immune to the Coronavirus?).

Once again, even if we assume that post-infection antibodies convey immunity, we still won't know (for months) how long those antibodies remain protective.

While we don't have direct evidence on SARS-CoV-2 (the virus that causes COVID-19), previous studies on another novel coronavirus -  MERS-CoV - have shown less-than-robust and short-term antibody development in survivors; particularly those with mild or asymptomatic infections.
  • A year later (May 2017) a report in the EID Journal: MERS-CoV Antibody Response After 1 Year, followed and tested 11 survivors of South Korea's 2015 MERS outbreak at 6 and 12 months, and like earlier studies, found that those with mild illness saw significant reduction in antibody titers over a year's time.
Not to be a complete wet blanket on the subject, none of this is to say that COVID-19 infection doesn't convey long standing immunity, or that an antibody test couldn't be useful in getting people back to work. 
Only that there are a lot of scientific and practical hurdles to overcome before we can rely on either of them. 
Late yesterday the World Health Organization released the following scientific brief on `Immunity Passports' for COVID-19, raising many of the same questions we've just gone over.

"Immunity passports" in the context of COVID-19 
Scientific Brief
24 April 2020
WHO has published guidance on adjusting public health and social measures for the next phase of the COVID-19 response.1 Some governments have suggested that the detection of antibodies to the SARS-CoV-2, the virus that causes COVID-19, could serve as the basis for an “immunity passport” or “risk-free certificate” that would enable individuals to travel or to return to work assuming that they are protected against re-infection. There is currently no evidence that people who have recovered from COVID-19 and have antibodies are protected from a second infection.
The measurement of antibodies specific to COVID-19
The development of immunity to a pathogen through natural infection is a multi-step process that typically takes place over 1-2 weeks. The body responds to a viral infection immediately with a non-specific innate response in which macrophages, neutrophils, and dendritic cells slow the progress of virus and may even prevent it from causing symptoms. This non-specific response is followed by an adaptive response where the body makes antibodies that specifically bind to the virus. These antibodies are proteins called immunoglobulins. The body also makes T-cells that recognize and eliminate other cells infected with the virus. This is called cellular immunity. This combined adaptive response may clear the virus from the body, and if the response is strong enough, may prevent progression to severe illness or re-infection by the same virus. This process is often measured by the presence of antibodies in blood.
WHO continues to review the evidence on antibody responses to SARS-CoV-2 infection.2-17 Most of these studies show that people who have recovered from infection have antibodies to the virus. However, some of these people have very low levels of neutralizing antibodies in their blood,4 suggesting that cellular immunity may also be critical for recovery. As of 24 April 2020, no study has evaluated whether the presence of antibodies to SARS-CoV-2 confers immunity to subsequent infection by this virus in humans.
Laboratory tests that detect antibodies to SARS-CoV-2 in people, including rapid immunodiagnostic tests, need further validation to determine their accuracy and reliability. Inaccurate immunodiagnostic tests may falsely categorize people in two ways. The first is that they may falsely label people who have been infected as negative, and the second is that people who have not been infected are falsely labelled as positive. Both errors have serious consequences and will affect control efforts.

These tests also need to accurately distinguish between past infections from SARS-CoV-2 and those caused by the known set of six human coronaviruses. Four of these viruses cause the common cold and circulate widely. The remaining two are the viruses that cause Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome. People infected by any one of these viruses may produce antibodies that cross-react with antibodies produced in response to infection with SARS-CoV-2.
Many countries are now testing for SARS-CoV-2 antibodies at the population level or in specific groups, such as health workers, close contacts of known cases, or within households.21 WHO supports these studies, as they are critical for understanding the extent of – and risk factors associated with – infection. These studies will provide data on the percentage of people with detectable COVID-19 antibodies, but most are not designed to determine whether those people are immune to secondary infections.
Other considerations
At this point in the pandemic, there is not enough evidence about the effectiveness of antibody-mediated immunity to guarantee the accuracy of an “immunity passport” or “risk-free certificate.” People who assume that they are immune to a second infection because they have received a positive test result may ignore public health advice. The use of such certificates may therefore increase the risks of continued transmission. As new evidence becomes available, WHO will update this scientific brief.