Immunity to coronavirus infection may help stem the pandemic

By Dr. Liji Thomas, MDApr 21 2020

The raging coronavirus pandemic is causing immense fear and uncertainty across the world. One of the most distressing aspects of COVID-19 disease is the seemingly large number of unknowns. These include the burning question of immunity. Does a person who was sick with the COVID-19 and then recovered or was infected without symptoms, have immunity against re-infection?

Getting the world back to work

The generally inadequate availability of testing means the vast majority of people who might have mild cases of the infection are not getting tested. This is unfortunate, because not only is diagnosis and quarantine delayed or even, but potentially useful information about the immune status of the patient after recovery from COVID-19 infection is lost.

As a result, most people don’t know whether they are still at risk or not and whether they could infect other people. There is also no way to tell how long such immunity will last. Researchers around the world are working on a rapid and sensitive test to tell whether a given person has developed immunity to the virus. Such people are called “corona blockers,” a person who can’t transmit the virus. However, the accuracy of such tests is still a question that awaits an answer, nor is the period of immunity clear.

If found to have a robust immunity, such corona blockers could, in theory, go back to work as ambulance drivers, police officers, and other frontline jobs. Doctors, nurses, and laboratory staff could also breathe freely as they treat people who are sick with the virus, being immune to it themselves and hence able to do more for the patients.

On the other hand, there are already a few reports of people having apparently recovered from COVID-19 only to fall sick with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) again.

Novel Coronavirus SARS-CoV-2 Colorized scanning electron micrograph of an apoptotic cell (blue) infected with SARS-COV-2 virus particles (red), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Testing for immunity

Immunologist Florian Krammer, who is part of a team that aims to bring out one such test, says his aim is to identify the immune population because “people who are immune could be the first people to go back to normal life and start everything up again.” Others like the virology team at the Queensland Institute of Medical Research are also racing the clock to find out more about how the virus works so they can block it, identify risk factors, test existing drugs for effectiveness, and test for immunity.

Krammer’s test is based on body fluids and is almost ready for use with patient samples in collaboration with Mount Sinai hospital. Since it doesn’t have to pass stringent FDA approvals, it could be seen in action very soon.

What are coronaviruses?

Coronaviruses are enveloped RNA viruses with genomes containing up to 32 kilobases of DNA. This makes them among the most significant viral genomes. The name coronavirus comes from the characteristic spikes on the viral envelope or covering (corona means “crown”). There are four genera of coronavirus, namely, he α, β, ɣ, and δ types. The first two are responsible for most human infections caused by about 30 specific coronaviruses. These account for the presence of coronavirus antibodies in about 30% to 60% of Chinese.

Most viral infections cause upper respiratory infections, which manifest as fever, headache, cough, and sometimes lung infection. On the other hand, SARS-CoV and MERS-CoV infections often cause no symptoms until the later stages, at which point the patient may present with pneumonia, shortness of breath, kidney failure, and sometimes death.

How immunity works in a coronavirus infection

Once a coronavirus enters the body, it attaches to the host cell through the DPP4R receptor, and its RNA appears in the host cell cytoplasm. This triggers an immune response that involves type 1 interferons and other inflammatory cytokines. Macrophages are infected following which they present the CoV antigen to immune T cells. The macrophages are part of the innate immune system. This works by recognizing pathogen-associated molecular patterns (PAMPs) through a variety of cell receptors.

Antigen presentation to the T cells leads to their activation. CD4+ T cells then activate B cells, which begin to produce specific antibodies against the virus. CD8+ T cells are cytotoxic and kill the cells that are infected by viruses.

Activated T cells begin to produce cytokines, which results in an immune-amplifying cascade of cellular signals. The persistence of the virus leads to ongoing cytokine release, which suppresses several subsets of T cells. CD8 T cells promote the production of antiviral proteins that can shield healthy cells from the virus. This can be inhibited by accessory viral proteins.

The interactions between viruses and infected cells lead to the production of large amounts of cytokines, including interleukins from the infected cells. The result is the recruitment of more immune cells, both lymphocytes, and leukocytes, to the site of infection, to destroy infected cells and neutralize the virus.

Harvesting hyperimmune plasma

And now, doctors are making use of this efficient, though time-intensive, immune response to help those who are desperately sick with COVID-19. Across the USA, a hundred laboratories have collaborated to produce convalescent plasma to stem the tide of COVID-19 patients. Having received FDA approval, US doctors can use compassionate care rules to give this plasma to patients.

In the UK, the NHS is planning to adapt the technique called passive immunization. Doctors will carefully harvest blood plasma from people who have had the illness and recovered and consequently have hyperimmune blood. This means they have high levels of anti-SARS-CoV-2 antibodies.

The plasma will come from convalescents who have recovered from the illness. The plasma will be used in the setting of several clinical trials, possibly funded by medical research funding organizations, such as the National Institute for Health Research. However, researchers can expect a swifter start-up for the trials than the normal months to years required for approval. This is because of the urgent need for a solution to the sheer number of cases (almost 20,000) overwhelming the UK’s healthcare system. This precious fluid will be used to treat patients with COVID-19 pneumonia to reduce the demand for ventilators, which are rapidly running out. Healthcare workers and family members of COVID-19 patients will also be offered plasma treatment to help arrest viral spread. This will ease the burden on the NHS.

Researcher David Tappin says, “Trials need to be undertaken, otherwise we will not know if this intervention is effective and worthwhile.” The trials will be conducted in parallel using convalescent plasma in several London hospitals. NHS Blood and Transplant have already started to look for convalescents who are eligible.

Experts feel the most significant effect could be seen when the plasma is given early in the course of the disease before the patient becomes severely sick. One specialist thinks the effect of a single infusion could keep the recipient immune for weeks on end.

However, says US infectious disease expert Arturo Casadevall, “The Chinese have been using it, and they are reporting good results, but it needs to be tested. This is not a panacea or a miracle cure; it’s something to try and put in place to see if we can help stem the epidemic.”