Understand the Pre-existing immunity to human coronaviruses

Understand the Pre-existing immunity to human coronaviruses 

The inclusion of T cell responses in COVID-19 vaccine design

Being so contagious, a new type of coronavirus should be contracted by almost everyone but still, this is not the case. Why not all of us and why not even every person in the same household, if one is already proved to be sick?

“There are four human coronaviruses — 229E, NL63, OC43, and HKU1 — that account for ~15% of common colds in humans. Adults may be infected with one of these on average every 2–3 years, such that there could be a degree of pre-existing cross-reactive immunity to SARS-CoV-2 antigens in these people, which offers a potential explanation for differing susceptibility to SARS-CoV-2 infection. 

If a host has a defense against SARS-CoV-2, the contribution of COVID-19 vaccine-boosted cross-reactive immune responses to vaccine-induced protective immunity comes to consideration.

Now we know several reasons for this unexpected outcome. First is that previous immunity is gained if a person already had any of four types of coronaviruses. Antibodies could be present and helped in the fight against new infections and cells have certain “memory” in ways how to initiate the right immune response. Another reason is immunity from our T cells which was explained before. They can recognize coronavirus and respond appropriately without causing a “cytokine storm”, a high-level immune response that negatively affects lungs as well as other organs and often leads to death.

Unfortunately, mild or asymptomatic patients usually have prolonged infection, since their immune response is fighting minutely and with peace for the whole body but the time of viral shedding is also longer. Therefore such patients could be more contagious, especially when not knowing that they are infected. 

Now let’s see what is said about herd immunity:

“It is estimated that 40–75% of infections may be mild or asymptomatic. .Asymptomatic and mildly ill individuals seem to develop low levels of antibody-mediated immunity has important implications for understanding herd immunity.”

The mechanism of infection is already known but a revaluation of our findings can help us better understand details since yet is unknown why some people stay healthy even when surrounded by covid19 patients.

“The initial site of infection of SARS-CoV-2 is the respiratory tract. On entry, SARS-CoV-2 interacts with the angiotensin-converting enzyme 2 (ACE2) receptor on bronchial and alveolar epithelial cells through its spike (S) protein receptor-binding domain (RBD), which is subsequently primed by a specific cellular serine protease, transmembrane protease serine 2 (TMPRSS2), to gain entry. Analysis of transcripts encoding ACE2 and TMPRSS2 by single-cell RNA sequencing has shown that these transcripts are co-expressed in various cell types and from autopsy studies SARS-CoV-2 can be detected in multiple organs, including the lungs, pharynx, heart, liver, brain, and kidneys. ”

We are bombarded by the news with statistics-how about many people died, how many are infected/sick/recovered. Yet we know so little about how will this affect postcode life-will we have a full organ capacity as it was before the sickness? Not allowed to explain details and raise panic, doctors talk little to nothing about the health after recovery. So far we know that developed countries have made rehabilitation clinics for patients to recover their motor skills. How much of our

lung capacity is lost after infection? Can we keep up with all activities we had before?

Below is an explanation of how neural responses are changed and how it affects immunity. 

“SARS-CoV-2 suppresses activation of the innate immune system, including dendritic cells and dampens antiviral type I and type III interferon responses.

IgM and IgG antibodies to SARS-CoV-2 are detectable within 1–2 weeks after the onset of symptoms in most infected individuals the magnitude of neutralizing antibody responses is positively correlated with disease severity.

The major target of neutralizing antibodies to coronaviruses is the S protein, which is composed of S1 and S2 domains. S1 is a membrane distal and contains the RBD that binds to the cellular receptor ACE2. S2 is membrane-proximal and has a role in membrane fusion.

Antibodies that bind to the S1 RBD block its interaction with ACE2, whereas those that bind to other regions of S1 and S2 can inhibit conformational change of the S protein and block membrane fusion, respectively. ”

References: https://www.nature.com/articles/s41577-020-00434-6#ref-CR17