Researchers in China, South Korea and Singapore have put together a significant amount of information about antibodies that human bodies release in their bloodstreams against the new coronavirus. The presence of these antibodies in the bloodstream could indicate that the person is infected with the virus, and researchers have used this immune response to develop new tests to detect COVID-19 infections faster than the genetic tests currently in prevalent use.
On April 4, the Indian Council of Medical Research issued an advisory “to start rapid antibody-based blood tests for COVID-19 in clusters (with containment zones) and in large [migrants’] gatherings [and at] evacuees’ centres”. The testing protocol is described in a chart:
That is, those who have presented with influenza-like illnesses could, after 14 days of being quarantined, could undergo an antibody-based test. If they test positive, they probably have COVID-19 and may need further hospitalisation. If they test negative, a genetic test (shown as RT-PCR) could be conducted to confirm or reject the result – or they could be quarantined for 14 days more before another antibody-based test.
Testing for antibodies is called serological testing. Such a test can identify who has been infected with the new coronavirus but cannot necessarily identify an active infection. The antibodies can be detected within three to four days after the symptoms develop, and are believed to stay on in the blood for at least a few months. The latter detail is interesting for a second reason.
We know that antibodies released to fight the causative agents of measles and mumps last for a long time in the blood, so once we get these diseases, we are unlikely to get them again. The antibodies against tetanus last for about a decade (which is why we repeat a tetanus shot after 10 years) – as do those against the 2002 SARS virus have lasted for a decade (although by some accounts this immunity could last for up to 17 years).
Health officials around the world have conducted numerous serological tests, adding to epidemiological data about the new coronavirus. Germany also has plans to test hundreds of thousands of people this way to ascertain the number of those infected, and the state of New York is expected to follow soon. Based on additional experiments, scientists have reason to believe humans could also become immune to the new coronavirus from the second infection onwards.
However, for now, we have no data about the duration of immunity against the new coronavirus after the first infection because it is a new pathogen.
Serological tests are substantially cheaper than the genetic test for the virus – called the reverse-transcriptase real-time polymerase chain reaction (RT-PCR) – and yield results within minutes. The serological test uses blood while RT-PCR testing is done from swabs collected from the nose, mouth or lung secretions.
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This said, serological tests are not easy to make. First, sections of proteins of the new coronavirus have to be produced in the laboratory to be used in an immunoassay test that detects whether antibodies are present. Expressing the protein in the right structure can be difficult.
Researchers have to choose those proteins for tests that will evoke a reaction from the antibodies as well as are not present in other coronaviruses. And most researchers agree the protein in the spikes of the coronavirus are likely to provoke the strongest antibody response. Another protein of interest is the coronavirus nucleocapsid protein.
Clinicians also understand that serological tests are not 100% reliable. As the flowchart above shows, the health ministry has made room for false positive and false negative results.
Serological tests can play an important role during a lockdown because they can be used to distinguish between those who do and don’t have an immunity to the new coronavirus. For example, all health personnel as well as workers who perform essential functions (including police and fire-fighters) could be tested to allow those with immunity to get back to the frontlines. Over time, they can also be used to assess what controls a lockdown should or shouldn’t have to allow the public situation to return to normal.
The tests can also identify prospective blood-plasma donors. Plasma is what is leftover after separating out various cells in blood, and contains antibodies and coagulant factors. Doctors have in the past transferred plasma from healthy individuals to extremely ill patients with three other viruses that cause hemorrhagic fevers, including ebola, to successfully treat their afflictions.
On March 27, a group of researchers from China reported a relevant pilot study published in the Journal of the American Medical Association. Their subjects were three men and two women critically ill with COVID-19, on ventilator support, and confirmed to have a high viral load despite antiviral treatment. The researchers transferred blood plasma from healthy individuals with adequate immunoglobulin G and immunoglobulin M in their blood, and whose antibodies had been confirmed to have antiviral activity. The conditions of all five people improved significantly, to the extent that they could be disconnected from their ventilators. Three of them have been discharged while two continue to be in hospital in stable condition.
The researchers concluded that plasma from previously infected people containing neutralising antibodies could improve the clinical condition of critically ill COVID-19 patients. However, they also acknowledge that theirs is an exploratory, pilot study (though not in as many words) and ask for further research to validate their findings.
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In a 2004 study, researchers used convalescent plasma to treat 80 of 339 people suspected to have the SARS virus. More patients were discharged on day 22 (58%) when convalescent plasma was administered before 14 days compared to 16% administered after 14 days. (There were no adverse effects.) The plasma had been obtained from people who had recovered from SARS. Mortality in the 80 people with convalescent plasma was 12.5% while overall mortality in SARS patients in Hong Kong at that time had been 17%. Like the study published on March 27, 2020, this one was also not randomised, so researchers could not make definitive statements about the effectiveness of blood plasma.
The SARS virus disappeared soon after, so no large-scale trial could be conducted – but the new coronavirus is still around, and researchers could conduct a randomised controlled trial to ascertain blood plasma’s potential to treat COVID-19.
Deepak Natarajan is a cardiologist based in New Delhi.