Immunity passport: A passport that does not take you places

By Maggie Chen and Kimmy Ye

As of June 28, 2020, there are more than 2.5 million confirmed cases of COVID-19 in the United States, and more than 780K are recovered. On average, 2000+ Americans get infected with COVID-19 each hour. As states continue to move forward to reopen the states, the concept of “Immunity passport” is brought to the public. Immunity passport refers to medical proof that would enable individuals to travel or to return to work after recovery from COVID-19 as they are protected by the antibodies from infection. The efficacy and the durability of the antibodies acquired from natural infection in recovered patients should still be discussed in detail.

Figure 1. Timeline of viral infection and two branches of immune response after a natural

infection.

How is immunity built? The development of immunity to a pathogen through natural infection is a multi-step process that typically takes place up to two weeks in previously healthy individuals (Figure 1). The innate response is early and non-specific: involving cells such as macrophages, neutrophils, and dendritic cells, it slows or halts the replication of viruses in the host, and in most infections, it may even prevent it from causing symptoms. Subsequently, the adaptive response, which involves cells such as T cell and B cell, kicks in after a week of infection to make antibodies called immunoglobulins (Ig). The antibody seroconversion changes IgM to other Ig isotypes in response to various signals and triggers. IgM and IgG are usually measured in viral infection settings, as IgM is the first antibody shown on B cell surface after an infection, and IgG is the most abundant Ig in humans and remains in the blood after an infection has passed. IgG indicates that the individual may have had COVID-19 in the recent past and have developed antibodies that may protect the host from future infection. When IgM is detected the person may still be infected, or you may have recently recovered from a COVID-19 infection. The adaptive response also establishes memory for the host to fight against infection. There are two major types of B cells: plasma cells and memory B cells. Plasma cells are responsible for antibody production and are short-lived, while memory B cells are long-lived and continue to circulate in the blood, waiting to combat reinfection. The adaptive response can also directly kill viruses by cells such as CD8+ cytotoxic T cells, which releases toxic molecules to kill infected cells and viruses.

Antibodies in COVID-19

Early research in rhesus monkeys and hamsters claim to observe immunity, evidenced by antibodies and no recurring sickness, which suggests the development of protective immunity. However, neither study specified on how long the protection could last. Furthermore, animal studies looking at human diseases must be taken with a grain of salt as results cannot be 100% applicable in human cases. In the rhesus monkey study, the data was considered weak as the infected monkeys did not not develop respiratory symptoms the way humans cases do. Additionally, while researchers could correlate memory antibody responses with reduced symptoms, the results did not indicate causal protection.

In humans, a study has shown that for a large proportion of individuals who recovered from COVID-19, the IgG and neutralizing antibodies levels start to decrease within 2–3 months after infection. However, the study size was small, including only 37 symptomatic cases and 37 asymptomatic cases. Consequently, there is insufficient information to claim whether a person can be reinfected by SARS-CoV-2, and for how long the antibodies can protect us from reinfection.

Reinfection in COVID-19

To date, no human reinfections with SARS-CoV-2 have been confirmed, yet there are reports from Asia claiming patients tested positive after discharge from hospital. Evidence of reinfection typically requires culturing evidence of a new infection following clearance of the preceding infection or evidence of reinfection with a molecularly distinct form of the identical virus. In one report, among two otherwise healthy individuals who had recovered from COVID-19 and had received negative results twice, viral RNA was detected again in throat swabs sporadically for up to 10 days. SARS-CoV-2 RNA has also been detected in the throat or nasopharyngeal almost three weeks after receiving negative results. In another report, among 18 patients, viral burdens were generally lower than values during peak of illness. At the time of post recovery positive test results, the patients self-reported alleviated symptoms compared to the prior infection. Although there has been no validated study and evidence on transmission during this stage, the possibility of transmission cannot be ruled out, especially for immunocompromised individuals. It is also possible these cases represent persistent or recrudescent COVID-19 illness or even true reinfection. This may be cause for concern as recovered patients may continue to shed virus despite being discharged from hospitals or home quarantining. Asymptomatic transmission could occur after recovery. However, it is too soon to use serological tests to determine whether individuals are immune to reinfection due to unresolved sensitivity and specificity issues. More studies of COVID-19 recovered patients are needed to monitor for signs and symptoms of recurrent illness.

Final comments: more unknowns await

To date, there is no data suggesting that the presence or the abundance of post-infection antibodies can protect an individual from getting a new infection for life. The virus is mutating rapidly as it infects human hosts and gets passed on to others. Some of the key mutations include the spike protein mutation, which can potentially lead to changes in viral entry pattern and infectivity as well as in immune responses. Moreover, recovery for some patients is just the beginning: there has been growing evidence of sequelae impairing patients’ overall physiology, and reinfection might not be the only concern in the second wave of outbreak. Therefore, development for safe, broad, and effective vaccines is more crucial than ever, as we cannot rely on “immunity passport” as a long-term protection for the population in COVID-19 setting.


Results from ongoing research and the current understanding of COVID-19 are constantly changing and growing. This post contains information that was last updated on June 28, 2020.





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