Coronavirus Mutations
Viruses constantly change through mutations and new variants are expected to appear over time. They can emerge or disappear or they can last forever. Multiple variants have caused the disease of COVID-19 and they continue to be discovered around the world with this pandemic. Coronaviruses are called this way because of the resemblance the spike proteins bear to a crown at it surface.
The SARS-CoV-2 is going through mutations and one should ask if the infectivity of the virus has changed because of its exposure to antibodies binding or to the phenomenon of neutralization. Multiple COVID-19 variants are circulating in the United States, In England and around the world. Three new variants have been discovered in the United Kingdom in September 2020 and in other countries like South Africa and Nigeria: The “N501Y” and the “D614G” mutations have raised concerns about the possible disastrous effects. These variants seem to spread more easily and more quickly. A rapid spread was noted in the south eastern part of England questioning the new vaccines efficacy. Hopefully, there is no evidence that a more severe disease or more illness and even more death is seen.
During the meantime, we all have friends or relative living in states like Tennessee, California or Georgia where COVID-19 cases have been on the rise. Hospitals, Healthcare clinics and Healthcare providers are overwhelmed, the same way we remember the healthcare providers in the states of New York and New Jersey, a little less than a year ago. Some patients are again unable to receive proper care although. Other areas may present with better news for a pandemic which can’t stop surprising us.
Routine genetic surveillance of viral outbreaks was suggested for years by public health officials in the United Sates. Nowadays, the most transmissible coronavirus variant pummeling in Britain has already been detected in more than 45 countries. These new variants only add more pressure on the distribution of the vaccines to the population in need. The problem is not only regarding the quantity available for injections but when politicians keep playing their political strategies, it hurts to be less effective. It is imperative that more people get vaccinated before more mutations undercut the effect of the vaccines. We may have more than 7 million to have already received at least one dose of a specific COVID-19 vaccine. Soon 300,000 would have received both doses.
The CDC has recommended that healthcare workers and nursing home residents be the first to receive the vaccine. This policy may be well followed in the state of Florida under the surveillance of a governor who works toward achieving the goals but others in different states continue to play their political games and chose who will receive the doses, bringing confusion to the process. Unfortunately, many individuals refuse to get vaccinated or are not too sure they will ever be ready to accept the benefits or the side effects of such vaccination. During the mean time the virus keeps mutating like it would be expected from any other virus with time.
Are these mutations more lethal? An increase in transmissibility could mean a higher death count even if the lethality remains the same. We become conscious that the transmissibility raises alarm and increase the visits in the health care centers. It is nice to read a little what a retired professor, Adnan Erol wrote in an article recently published in the Journal Immunological Letters: “Are the emerging SARS-CoV-2 mutations friend or foe?”.
In this article, he argues that the mutations may not be entirely unfavorable to humans. We remember well that the SARS-CoV-2 uses its spike proteins (S1 and S2). (S1) to binds any human receptor like ACE2, or neuropilin-1or CD147/basigin, then the S2 subunit spike catalyzes the coronavirus’s fusion with the human cell membrane and set up the infection.
The D614G mutation was discovered in Europe and the 614 th amino acid mutated from the aspartic acid position (D) to the glycine (G) and soon that mutation become dominant in the world. The virus transmissibility and virulence was demonstrated also in animal experiments exposed to the virus (mice, non-human primate and human). Circulating antibodies made of B-cells will bind and neutralize the viruses or other microbes. So the D614G is more infectious, indeed but more vulnerable to antibody neutralization than the original strain of SARS-CoV-2. The mutation causes the virus to attack the cell more efficiently but the virus itself is more easily destroyed by the antibodies.
SARS-CoV-2 in its D614G mutation would increase the viral replication while the COVID-19 infected patients have more viral RNA. The severity of the disease and the mortality rate will not change because the mutations expose the virus to antibody for neutralization.
A second type of mutation, the N501Y is also rapidly spreading in London and south-east England. In this new strain, the Asparagine (N) is substituted to Tyrosine (Y) in position 501. This new strain has caused more than 60% of SARS-CoV-2 infection in the London area as reported by the England’s chief medical officer Chris Witty. This strain is more efficient at infecting cells but Professor Erol believes also that it becomes more prone to antibody neutralization. This theory has only been supported by computer data so far although more animal studies or cell cultures are on the way. It appears that the N501Y strain is not more deadly to the cells as it infects more efficiently delivering a viral load is 3-times higher than the original strain of SARS-CoV-2. Indeed, Pfizer mRNA vaccine works well against on this strain and antibodies isolated from vaccinated persons have effectively neutralized both strains, the original and the N501Y. The country of England has initiated a new lockdown to face this mutant virus.
A third mutation is detected through a most alarming form in South Africa, the E484K and appeared to have spread in many other nations as well. Like the other new mutations, it is thought to be more transmissible than the original form of coronavirus which emerged in China. There again, it does not appear to cause a more severe disease.
So the new variants have shown how they can spread quickly, bringing faster a disease from which we have learned so much over a year. The victims respond well to the actual known treatments. We have heard all the negative things from SARS-CoV-2 strains or its variants, such as the D614G, N501Y and E484K mutations. The increased infectivity and transmissibility from these mutations is indeed a cause for alarm, since more cases equal to a higher death counts. However, it’s also fortunate that these mutations render the SARS-CoV-2 weaker against the immune system, because with these mutations, it becomes more susceptible to antibody neutralization. Otherwise, the increased viral replication and shedding leading to a more lethal Covid-19 disease, is not seen. Overall, although there is an increased transmission from the D614G, N501Y and E484K mutations, which is unfortunate but we can be glad that the disease severity and the death rate are not any worse.
Can we be surprised if this coronavirus last for years.? I was discussing with my colleagues at the AMHE and I opinionated in giving my impression that this virus may last another six to eight more month. We have learned on the pattern exhibited by the SARS-1, perhaps. Obviously, I am not the finest expert but I was the only one addressing our board of trustee at the AMHE as well as the Central Executive Committee (CEC) to implore the last July 2020 cancellation of the annual convention as soon as the Olympic Games were postponed in a world debate. We understood the seriousness of this pandemic disease which was about to impact the world. I do believe that with the changes in the virus, we may be ready in a half of a year to resume our regular activities. The AMHE convention in 2021 will need as well to be as well postponed or cancelled ot find another alternative for our summer activities, next July 2021.
Every day, patients with the COVID-19 are being treated and released from the hospital, but even if many are tested negative for the SARS-CoV-2, it is far from saying that they have fully recovered. Almost 30% of the one treated will vegetate for a wild stage called “Long-Covid” in which a patient discharged from a hospital with a negative test for the virus, still present signs of shortness of breath, extreme fatigue, joint pain, myalgia, cognitive behavior as well as gastrointestinal or cardiac problems. This has been proven in fact, that many patients with “Long-Covid” may have never been hospitalized.
We are aware now that antibodies take around 3 weeks at least to form after the established infection and the CDC has shown that these antibodies specific to SARS-CoV-2 were also discovered in donated blood samples (Dec 2019). Countries like Brazil China, Italy and Spain have even found the evidence that COVID-19 has appeared even before this date. Scientists understand now why the SARS-CoV-2 genomes were already so stable during the early months of the year 2020. The COVID-19 vaccines are safe and do not contain the actual virus, so they can’t transmit the disease. More, monoclonal antibodies are being tested in the laboratory to provide more immunologic help and prevent the SARS-CoV-2 virus from entering a healthy cell. These monoclonal antibodies can’t cause COVID-19 either.
Meanwhile, experts rally to speed up vaccination around the world. There are in the pipeline at least 20 vaccines in phase 3 trails, seven for limited use and three already approved for full use in different countries: Pfizer-BioNtech, Moderna, and Oxford-AstraZeneca. This last one is approved for use only in the United Kingdom. The vaccine rollout has been slow around the world at the exception of the state of Connecticut perhaps. In the United Kingdom where the N501Y strain was found to be more contagious but did not seem to be the cause for a more severe disease.
Controversial changes in the dosing guidelines are seen when one wants to delay the timing of the second dose or another one wants to allow mixing or matching vaccine between the two doses. More, it is question that the actual vaccine may become also available at different retail pharmacies like CVS, Walgreens, Rite Aid and even Costco to enhance the process of vaccination. In fact, it may be soon distributed at more than 40,000 pharmacies as mentioned by the Health Secretary Alex Azar. Even Walmart just claimed their willingness to help in the distribution of the vaccine. Many are waiting for the Johnson and Johnson vaccine which will require only one injection.
Anthoni Fauci, one of our expert in the USA, states that he would not delay the second dose and agrees with the Center for Disease Control and Prevention (CDC) that the vaccines are not interchangeable and should not be mixed in their dosage. Concerns about a vaccine shortage may have the authorities at the National Institute of Health (NIH) look for the possibilities to stretch the vaccine supply, like using half of a dose to vaccinate.
In Brazil, a Chinese Sinovac Biotech vaccine was found to be 78% effective after it was reported that 13,000 volunteers enrolled to take the vaccine in July 2020. The facts remain that 218 Covid-19 cases were discovered in the group but 160 of those infected cases had received a placebo. The conclusions have brought doubts on the transparency of this study.
In December 2020, other researchers from Sinovac presented a vaccine with a 91% effectivity after a large trial was conducted in Turkey with 752 volunteers receiving the vaccine while again 570 got the placebo. There are a lot of questions about this trial as well. In anyway, Sinovac is ready to supply Indonesia, Turkey, Chile, Singapore, Ukraine and Thailand as reported by the New York Times.
Finally, India just approved it first Covid-19 vaccines from Oxford-AstraZeneca” for emergency use only. This vaccine was approved before even collecting data on the Phase 3 trial, bringing doubts and sharp criticism.
Around the world we are all looking for a way to obtain a “Herd Immunity”. This is a term that has been used when it is possible to eliminate a pathogen especially when almost everybody has already been infected by it. The country of Sweden has adopted such model at the beginning of the pandemic with purposely leaving the population unprotected in the hope that a maximum of subjects will catch the virus. This concept was promoted but how can we be sure of reaching the desired level?
With the vaccines presently on the market for distribution at great scale, this is our last hope to reach this level of Herd Immunity, but for how long? We don’t even know how long natural immunity or immunity simply to an actual vaccine will last. We don’t know how many individuals can or will become immunized even after taking both doses. More, we don’t know if the virus will evolve to become resistant to all vaccines. Many have a better use of the term “herd protection”. If we have a choice, it is definitely better to receive the vaccine than to become the victim of the infection.
Nobody can tell how long they will remain protected after contacting the infection or after receiving the vaccine. Possibly there may be different pathways to reach this status of protection. New York and New Jersey have learned how to manage the pandemic earlier in the year 2020 but the cases and hospitalizations are rising gain. They have learned from their mistakes hopefully. We have already been under a year of confinement and protection against a virus we are still learning how to avoid and treat.
I am looking for the time to take my second dose of Moderna vaccine at the end of the month, like many of us on the front line and many old patients in the nursing home or with comorbidities have already. Meanwhile it is reported that the Pfizer-BioNtech COVID-19 vaccine is likely to be effective against the new contagious variant strain discovered in the United Kingdom but this search has not been peer-reviewed yet and there is no independent study on any vaccine’s effectiveness against the variant published either. This variant could become the dominant form of the virus.
How many more friends will keep on losing their life in the line of duty, while taking care of patients with COVID-19? I hope that all will be able to appreciate the beneficial effects of a vaccine. To the one refusing to take it, you place many others at risk if you contact the disease and your chances in becoming a victim of this virus or its mutated forms increase every day. Please get vaccinated, wear your mask, avoid non-essential activities and keep being confined for your well-being.
This week, we have lost at the AMHE two physicians husband and wife in New-York, one in Florida, one in Montreal and we have at least ten (5) others newly infected with the virus. We remain concerned about those new and more transmissible forms which are emerging and spreading so easily, knowing well they may become the dominant strain.
May I conclude in repeating the words of Cicero to Catalina: … “Usque Tandem Abutere COVID-19 Patientia Nostra”!… More than two (2) million have already died worldwide in this pandemic since the impact of this highly transmissible virus. The United States has accounted almost 400 thousand deaths. Haiti may be privileged for not having more victims, but the fact that nobody is practicing social distancing and the refusal of a population to wear a mask, have placed us at risk or allowing the majority perhaps to reach that herd immunity. Notre Dame du Perpetuel Secours is certainly watching over our country like she did in 1882 during the epidemic of “Petite Verole”. Haiti remains with less than 240 deaths and a little more than 3000 infected by the virus.
Maxime Coles MD
Boca Raton FL