In July, a large seroprevalence study in Mumbai reported that 57% slum residents and 16% building residents had antibodies to SARS-CoV-2. The presence of antibodies implied that these individuals had been infected, and had now developed protective antibodies. Similar results were found in other cities, leading to optimism that “herd immunity,” the protection that a community enjoys from a germ by virtue of a significant proportion of individuals being immune, was not a distant dream.
Optimism on hold
Two recent changes have put such optimism on hold: Reinfections being reported across the world and declining seroprevalence of antibodies in repeat sampling surveys done in both Mumbai and Delhi. The latter suggests a possible “decay” of antibodies with time.
Nasal and throat swabs for SARS-CoV-2 can remain positive due to dead viral RNA for over 2 months, but such re-positivity does not imply reinfection. A true reinfection is one in which the viral genome in the second infection differs from that of the first. Proving this necessitates the whole genome sequencing of both viral strains, a research tool that is not accessible routinely to healthcare providers. Clues to a possible reinfection include more severe disease (both clinically and on laboratory investigations) and a lower cycling threshold value (which may reflect an increased quantum of virus) on the RT-PCR test done during the second episode. A negative swab between the two episodes helps further distinguish re-positives from reinfections. Instead of RT-PCR for viral RNA, which detects live and dead virus, subgenomic messenger RNA, a product of actively replicating virus, can be used to detect viable virus.
Forms of immunity
Two forms of immunity defend the body from reinfection: antibody-mediated (through immunoglobulins, which recognise parts of the virus and neutralise it), and cell-mediated (through cells such as T-cells which can induce death of virus-infected cells). Antibodies could either be binding antibodies (which bind to the virus and sensitise the immune system) or neutralising antibodies (which directly bind to the virus and interfere with its function). Unlike antibodies induced by SARS-CoV and MERS-CoV (the causative viruses of the 2003 and 2012 outbreaks, respectively) that lasted a minimum of 1-2 years, studies have demonstrated the rapid waning of antibodies after infection from SARS-CoV-2. Does this mean that such individuals are susceptible to reinfection? Not necessarily. Most commercial antibody tests detect binding antibodies, while immunological memory is more accurately reflected by the presence of neutralising antibodies. Secondly, the role of cell-mediated immunity has not been elucidated yet. A study from France by Gallais et al. demonstrated the evidence of cell-mediated immunity among family contacts of individuals with COVID-19, despite such individuals having undetectable antibodies. Similar studies for SARS-CoV have demonstrated evidence of cell-mediated immunity for over a decade (despite waning antibodies). However, the presence of cell-mediated immunity is not routinely measurable, and unfortunately, it isn’t guaranteed to ensure immunity either. One does hope, though, that such immunological memory has a role in protecting from reinfections.
The implications of what we know thus far are manifold. It must be pointed out that after 8 months of the pandemic, reinfections still seem exceedingly rare. However, an individual who has recovered from an episode of COVID-19 needs to be cognisant of the fact that recovery does not ensure immunity, and keep up the precautions of masking, physical distancing and hand sanitising need to continue unabated. From a healthcare provider’s perspective, we now know that the constellation of symptoms and signs that make us suspect the possibility of COVID-19 disease needs to be investigated, irrespective of whether the patient has already had the disease. From a community perspective, we need to rethink the constructs of immunity passports, herd immunity and vaccination strategies, taking into account the possibility that with the passage of time, immunity, whether induced by infection or vaccination, may wane, and reinfections/vaccine failures may become more common.
The SARS-CoV-2 virus continues to outsmart us, and till the time that an effective vaccine which confers long-lasting immunity is available, a world with the virus will continue to haunt us, like the lyrics of a famous song: “You can check out any time you like, but you can never leave!”.
(Dr. Lancelot Pinto is a Consultant Pulmonologist and Epidemiologist at P.D. Hinduja National Hospital, Mumbai.
Dr. Camilla Rodrigues is a Consultant Microbiologist and Head of the Department of Microbiology at P.D. Hinduja National Hospital, Mumbai.
Views are personal.)