Covid-19 bowls a re-infection googly

When the virus enters the body, the immune response that is most evident and often studied is the systemic response of circulating antibodies and cellular immunity.

Trust the SARS-CoV-2 virus to be the tormenting trickster with a bagful of nasty surprises. We are just getting used to a wellspring of evidence that regularly challenges and shatters early assumptions. We have seen how this ‘respiratory virus’ reveals whole-body pathology, spreads by aerosols besides droplets, affects children besides adults, troubles through chronic sequelae even after apparent recovery from an acute infection (‘long Covid’) and continues to give positive viral test results through ‘dead viruses’.

The latest surprise to be delivered by this virus is a reported case of ‘reinfection’ in Hong Kong. A 33-year-old man had a diagnosed Covid-19 infection four-and-half months ago, with symptoms and a positive test, and recovered uneventfully. After his recent return to Hong Kong from foreign travel, he was tested at the airport as part of the surveillance protocol there. The nasal swab tested positive for the Covid-19 virus. The genetic signature of this virus was different from the earlier one, meaning that he had acquired it from a different person than during the initial infection.

This time around the person was asymptomatic and remained so. The consternation that greeted this report was because of the concern that acquired immunity appeared to be short-lived and not protective against reinfection. Does it mean that this virus can cause repeated infection as it recycles through different human beings at different times? Questions were raised about the value of a vaccine if the immunity conferred is so short-lived.

Questions about reinfection were raised even earlier when reports had come in a few months ago from South Korea, China and Europe that some people who had tested positive for the virus in an RT-PCR test, and had clinically recovered, tested positive again in that test a few weeks later. Some of them had tested negative infection in between. Most had antibodies present as evidence of the immune defence. Whether the repeated test positivity was due to ‘reinfection’, ‘reactivation’ or a ‘false-positive test result’ was debated. After detailed evaluation and scrutiny of case records, South Korean scientists announced that these repeat positive tests were due to ‘dead viruses’ and should be considered as ‘false positive’. Other countries soon concurred.

The case in Hong Kong is different. It is a well-documented case of a new infection with a virus that bears a different genetic signature. When a virus passes through a human body and hijacks the host’s genetic material to replicate itself, it exits the body with a genetic signature that shows some change that is traceable to that person. This helps to trace the human source when it infects others. The Hong Kong viral detectives noted this vital clue to declare it a new intruder and not a zombie version of the old one. If the person had not been screened at the airport, the second infection would not even have been recognised as he was asymptomatic. Happenstance!

Why does this happen, if immunity is supposed to last long? We need to understand the intricacies of the immune response to unravel this. Apart from innate immunity, which is the body’s initial non-specific response to a microbial invader, specific adaptive immunity is acquired by the body in response to the infective virus or a vaccine. This tailored response provides the second stage of the body’s immune response to the virus when it enters the body. The entry of the virus into the nose or mouth may not be thwarted by the virus, but the subsequent damage is prevented. To put it simply, the initial ‘infection ‘is not prevented, but the subsequent ‘disease’ is.

Should this surprise us? If we flip back a few weeks to the initial results of the Oxford vaccine trials, early-stage animal studies in chimpanzees had shown that the chimps had produced high levels of anti-viral antibodies, but nasal swabs still tested positive for the Covid-19 virus. This raised questions on the efficacy of the vaccine, but Oxford’s researchers countered by saying that the strong immune response would still prevent the disease.

When the virus enters the body, the immune response that is most evident and often studied is the systemic response of circulating antibodies and cellular immunity. The antibody-mediated immunity consists of immunoglobulins IgM and IgG, secreted by bone marrow-derived B lymphocytes. The former is short-lived, beginning to rise early in the second week of the infection and fading in the fourth week. The latter is detectable late in the second, peaks by four weeks and then declines to fade away by three months. Cellular immunity is provided by T lymphocytes, which are originally derived from the thymus gland. Lymphoid tissues, which are widely distributed in the body, produce both types of immunity, to provide the body’s defence against unwelcome microbial invaders.

The encounter with the virus also evokes another response. Even as ‘neutralising antibodies’ bind to the virus to immobilise it and ‘killer T cells’ battle with it, the intelligence agencies of the immune system begin to store recognition patterns of the virus for future reference. These are the ‘memory B cells’ and the ‘memory T cells’. Like the rogues gallery in a police station, the images of the past offending viruses are stored in these cells. The neutralising antibody levels may decline in three months after the battle has been won, but any fresh invasion would gain instant recognition by the ‘memory B cells’ and quick mobilisation of the specific immune response that is pre-programmed to tackle this virus. The entry into the nose may not be prevented, but the damage to the body will be. The thief may have entered the compound, but cannot rob the house as the alarms have gone off and the guards alerted. The strength of this recall response will vary between persons, based on the vitality of their immune systems.

Can we even prevent the virus from even infecting again? Since the virus enters through the nose or mouth, it has to be tackled there, by ‘secretory antibodies’ to thwart any attempt to gain even an initial foothold. These belong to the class of IgA antibodies. If these are available locally in the nose or mouth, the virus can be rebuffed even at entry. We can then achieve prevention of the infection, not just of the disease. The compound wall itself is electrified to spurn the intruder.

The vaccines currently under clinical trials are ‘systemic vaccines’ administered into the circulation through the intramuscular or intradermal route. The immune response is strong in the form of circulating antibodies (IgG) which can neutralise the virus as it moves within the body. They cannot stop the virus from settling on the nasal epithelium. For secretory antibodies, which can stop the virus even at the entry points, we need IgA antibodies. To stimulate these antibodies, we need ‘mucosal vaccines’ which can be introduced through nasal inhalation. Such vaccines are under development, but are not yet in clinical trials.

Some scientists believe that administering both the systemic and mucosal vaccines may provide the best defence against the virus. However, any vaccine has to prove its value and safety in a rigorous clinical trial. Fascinating as the studies of human immunology are, the tests of public health relevance and impact have to be passed before any vaccine is cleared. Till then, we have to maintain vigilance against the first bout of Covid-19 infection and draw assurance from the fact that our immune system is programmed to deal with reinfections. Best to avoid the first infection, but should it occur and be followed by reinfection, our bodies would be well trained to deal with the googlies bowled by this tricky virus.

The author is President, Public Health Foundation of India (PHFI), and author of Make Health in India: Reaching a Billion Plus. Views are personal