Reinfection and the endemic potential of COVID-19November 9, 2020
We have seen several reports of reinfections in which an individual has been subjected to SARS-CoV-2 infection more than once. The persistence and ubiquity of common respiratory viruses like influenza, rhinovirus respiratory syncytial virus (RSV) etc are due to their ability to infect repeatedly. It is therefore important to consider the possibility that SARS-CoV-2 may turn endemic.
In most cases, the human immune system develops a defense mechanism — including immunoglobulins, memory B lymphocytes and memory T cells — after an initial infection. This adaptive immune system must identify any reinfection and be able to prevent a re-entry by the virus. However, several viruses may evade the immune response, or may generate an insufficient response. Serological studies suggest that SARS-CoV-2 infections can induce antibodies. However, early results from experimental vaccination in primates suggest that these antibodies may not be sufficient for long-term protection or to activate the adaptive immune system. It is also known that SARS-CoV-2 infection is heterogeneous — with a range of reactions from the asymptomatic to the very severe. It is possible that some of these individuals may never develop immunity against the infection.
There is also the waning immunity, in which the initial adaptive immune response is robust, but its potency disappears over time, leaving the host vulnerable to reinfection. The virus’ immune escape process can be due to serial passage through the host population, accumulating several point mutations. These mutations result in antigenic drift leading to conformational changes of viral surface proteins, disrupting the binding capabilities of previously generated antibodies and enabling reinfection. Other endemic human coronaviruses (HCoVs) like OC43, HKU1m 229E and NL63 indicate that reinfection is common within a year. In contrast, many pathogens which cause severe systemic effects elicit a long-lasting adaptive immune response, as seen in SARS survivors who have neutralising antibodies persisting for 2-5 years. Therefore, the severity of reinfection may influence the duration of protective immunity and long-term effects of SARS-CoV-2. To date, the responses among some patients reinfected by SARS-CoV-2 have been heterogeneous, including rare hospitalisations. Thus, serological and prospective studies are needed to determine the pathogenic severity and immune capability in reinfections. Should repeat infections become common, SARS-CoV-2 will likely become endemic outside vaccinated areas. The typical timelines when an individual experiences reinfection and seasonal differences in transmissibility will determine the pattern of endemicity. Other than in tropical areas, respiratory viral infections are common during cold weather. We know that in case of influenza, infections are the highest during the winter season when people are together and indoors for longer periods. On a large scale, co-occurring and overlapping infections of influenza and SARS-COV-2 will pose a serious public health problem. However, if non-pharmaceutical interventions are adopted to mitigate SARS-CoV-2, it may reduce the magnitude of influenza infections. The seasonal occurrence and magnitude of infections of not just one pathogen but multi-pathogen system may need important studies of interaction dynamics at the clinical and molecular levels. The overlapping phases of infection between two or more pathogens may help in enhancing each other’s transmission and cross-neutralize, or have a devastating effect. All these possibilities need to be evaluated and large-scale studies are needed as environmental changes are imminent and we need to be prepared to face oncoming challenges.