SARS-CoV-2 and Immunity
|The American presidential election is well on the way and already more than 90 million of people have placed their vote while the COVID-19 continues to impose its will on the population, infecting more than 8.86 million and claiming 230,000 in the United States. The figures are also alarming in the remaining world: 45 million of infected cases and more than 1.2 million deaths. More than 3.6 million Americans have recovered from the disease while 30.2 million have recovered in the world. Politicians are playing a blame game with each other for the lost victims like if they have better solutions to stop the pandemic. Businesses are still closed and schools are trying to keep their doors open allowing a younger population to face the disease and resume a more normal life in resuming their classes. Number of cases have surged across most European countries like Germany, France, Spain, and across the United States still, we are looking for a better way to fight the virus. The scale of the recent outbreaks may be really different.
Two countries Canada and Germany have done a better job in restricting their citizens from freely socializing more than their neighbors. Germany has kept the gyms, bars and restaurants closed for weeks while we are opening ours in the United States. Germany is also on its way to provide free testing widely for all its citizens. Canada may have done even better in keeping closed all restaurants and bars, and in imposing the mandatory wear of masks in line with social distancing. Canadians are more deferent to the authorities and have accepted better these restrictions on their private life. More, the East Canadian provinces like Nova Scotia, Ile du Prince Edouard, New Brunswick and the Labrador-Newfoundland all, have also closed their doors and practiced social distancing and the wear of masks. Many other countries have also kept their borders closed like Australia, Ghana, Taiwan and Vietnam, and have done well in the control of the virus. France just re-imposed a nationwide lockdown with curfews for at least a month with re-closure of bars and restaurants. They are even banning gatherings but they are still keeping the schools open. A curfew was imposed in the town of Philadelphia not because of the COVID-19 but because of political unrest after a 27-year-old black man was shot down by a policeman. There is a crisis throughout the world which has produced a vacuum power.
Everywhere we listen to speeches of politicians selling themselves to a public, unable to make the difference with a virus which is imposing his will with or without any possibility of control. This leave us with a more important problem, the one facing the Immunity. The questions remain: Are we reaching an Immune state once we recovered from the disease? Are we better protected once treatment is provided against the COVID-19? Is the protection immediate upon entering in contact with the virus? Is the vaccine the ultimate solution to our problem?
We understand the disease better but we are still learning so much about this pandemic. Studies did show that after catching the disease and recovering with or without any treatment, our immune system has that faculty to form antibodies. No matter the kind of antibody but IgG, IgM, IgA can be detected in the system three to four weeks after recovering from the disease. It is certainly the proof that an individual is infected or not but also the proof that he has recovered from the disease. What we do not know well is why the antibodies disappear after 4 weeks. Why are these antibodies not seen 6 months or even 6 years after like we have noted in other viral disease? This would have been proof of a certain immunity in relation to time.
It is true that not too many cases of re-infections have been reported all over the world. Why? In some, a modified virus was discovered with less virulence, in others it seems that the recurrent disease has imposed a death sentence on the one who contracted it again. Our scientists are looking at answers and even compared it to the way the Ebola virus has impacted their victims and the reaction it has inflicted to the immune system. Are there any markers available? The United States is far exceeding numbers of cases and number of deaths due to the disease reported by other big countries. It seems that even China has by manu military isolated its population and appears to have done better than the USA. We will always ask why we did so poorly? We had problems with testing, problems with protective equipment for our health workers. So much went wrong. Hopefully, we have enormous capability in healthcare capabilities and we have the best biomechanical system in the world/ One will easily pass the problems to a lack of leadership. In anyway, like we say in French, “Avec SI, nous pouvons mettre Paris en bouteille”. It is easy to critic but performing is an art that require skills and cooperation. As physicians, we know better our limitations and COVID-19 has been a puzzle that we are not ready yet to solve. The truth is that we are observing a federal government which has largely abandoned the control of the disease to the states authorities.
As physicians, it is more important to center our effort at saving life. Our immune system brings many types of white blood cells or lymphocytes to defend the body against an invader, this represent our defense mechanism. More, there are B and T lymphocytes which manufacture antibodies to fight the invading virus or bring killer cells to attack the antigens. They will help our organism in boosting its immune system by releasing chemicals like cytokines. The helper cells assist the B cells in the production of antibodies.
It is believed that most infected persons who may have been in contact with the virus, have the power of generating antibodies. Others may develop neutralizing antibodies which defend the cell itself against the harmful effects of the virus. The term protective antibody has been used to discuss the effects of those specific antibodies. The vaccines will enhance the capabilities of the neutralizing antibodies to provide a natural immunologic response to the infection
Individual T cells react differently for each individual affected by the virus. A recent study performed in La Jolla Ca, carried among infected COVID-19 patients, has demonstrated that individuals who presented a strong specific T cell response were victims to a milder disease compared to the one with a less reactive T cell response who reacted poorly to the disease. This seems to explain why anybody older than 65 were found to have a higher risk for the infection.
Ten months already into the pandemic, and not much physical changes has been seen in this virus and little difference in the structure itself. Some believes that there is little mutation not altering the morphology of the virus but remain unable to explain the shifting in the age of the victims. The more than 65 are no longer the most affected age group but an intermediate group 45 and younger appears to be more affected. The return to school on the campus of the students at the university, the return to work on assembly line has certainly increased the numbers of positive cases but not the numbers of infected cases. Because the virus has not mutated quickly, it is expected that the vaccine will provide adequate passive protection to the population.
The problem with the immunity is simply the fact that nobody can predict how long it will last. Previous studies may have already demonstrated the existence of antibodies in the blood of recovered COVID-19 patients at last during the next three (3) to (4) weeks after the infection while a more recent Canadian study on recovered patients, has clearly found antibodies after (4) to (6) weeks of convalescence. Recently again, another study has reported antibodies 4 months after the beginning of the symptoms. In fact, nobody can assert what level of antibodies is needed to assume protection. A quantitative test may be needed while we are learning on this pandemic.
The United States just set a record high of 90,000 cases diagnosed in a day. One will say they are diagnosed but not infected cases especially in the mid-west and the south of the country. With the Flu season already knocking at our doors, more precautions will be needed because the symptoms overlap. More sophisticated tests may be needed to diagnose both viral diseases, perhaps with a swab.
We know enough about co-morbidity in the old population and the sick in our nursing homes but we are unable to predict the one who can or can’t contract the disease depending on their immune response. The vaccines will play an important role and may be able to answer some of those questions. What make us a victim during a first infection? How many times we can get re-infected? and why are we not able of being protected with functional antibodies? Our immune system has produced antibodies during the course of the infection. but why are they not lasting more than 3 or 4 months? Why can’t we obtain a permanent immunity?
Physicians have learned so much from other coronavirus diseases like MERS and they tried to apply the lessons to the treatment of COVID-19. The CDC has also revised so many times their recommendations in the way to approach a patient during this pandemic. Physicians have learned to avoid abusing too early ventilators, antibiotics and anti-coagulants have been used in the first stages followed by anti-inflammatory inhalation medications, later Remdesivir for the viral storm. The experience we have gained with MERS on Convalescent Plasma/ has allowed physicians to surely save life. Although many medications like the interferons, the Interleukins, Lopinar etc. may still be experimental in nature, but they have been used in many centers around the world. Time will tell if we will be able to learn and control the side effects.
In a study on 117 convalescent patients who survived the Ebola infection, it was proven that half of the patients were able to demonstrate in their blood, the presence of neutralizing antibodies believed to be protective helper T cells. Virus monoclonal antibodies are predicted to reduce the viral load ameliorating the symptoms and avoiding any hospitalization. It is different when dealing with a patient suffering from severe COVID-19, recent studies have shown that the immune system may attack itself creating “autoantibodies” targeting other healthy human cells instead of the virus exactly the way it is seen in auto immune diseases like Rheumatoid arthritis and Lupus. Those are the conclusions of an Immunologist at Emory University in Atlanta, Matthew Woodruff. In his study, he reviewed 52 patients with severe COVID-19 and found the autoantibodies were present in more than half. These autoantibodies were associated with blood clotting, affecting the vascular flow and creating a longtime effect. Nobody have found a way to cure Lupus or Rheumatoid arthritis. These conditions can flair and relapse but never cured. It may not be surprising to see the same trend in milder form of this viral disease.
In England a large study on 365,000 people in contact with the SARS-CoV-2 virus between mid-June 2020 and mid-September 2020 has demonstrated that the antibodies decline over a three-month period, but they did not build an immunity. The older the patient was, the faster the antibodies had the tendency in disappearing from the system. The study was called REACT (Real-time assessment of community transmission). Nobody can assert how many can be subject to re-infection with the virus but it is important that everybody continue to take supplementary precautions to reduce the risks to themselves and others. This remains our puzzle to resolve because there is no way to assure a “Herd Immunity” in allowing a large population to become immune. We do know that perhaps 60% of the population will have to become infected in order to claim any degree of immunity in a given population. If the disease does not allow us to build up that immunity by stimulating the formation of antibodies, our last hope is through the vaccination. This should allow the infection rate to go down. It is definitively unclear at what level of immunity the antibodies provide … and for how long. Being tested positive for antibodies does not mean that you do not need to follow the guidelines of wearing face masks or social distancing. Dr. Bhattacharya of the University of Arizona states that the production of antibodies is bi-phasic with a sharp rise in their concentration then a sharp decline followed by a more consistent production.
Maxime Coles MD
Boca Raton fL