As described previously, the omicron variant of the SARS-CoV-2 virus that causes Covid-19 has become dominant1,2. On 25 November 2021, the African Union and Africa Centres for Disease Control and Prevention released a statement that identified the newest variant of concern, the omicron variant, also known as the B.1.1.529 variant2. Since then it has continued to mutate, producing subvariants (BA.1 and BA.2) that became predominant, causing more infections but less severe symptoms in most people earlier this year3. In May, two new lineages (subvariants) were identified4,5. They were designated as BA.4 and BA.5. The BA.5 subvariant has become dominant. On 9 July, 65.0 % of all infections in the USA were due to BA.56. It has spread fast. On 30 April, it accounted for only 0.2% of SARS-CoV2 infections.
So, people want to know if their vaccine or natural immunity can protect them. Researchers have started to determine the amount of antibodies (antibody titers) against BA.5 in blood sera obtained from various people7-10. These antibodies are part of the innate immune system that works with the acquired immune system to fight infections by vaccines, bacteria and other pathogens11. The studies showed that the BA.5 subvariant was able to escape neutralization by antibodies in many people who had been previously vaccinated or been hospitalized after being exposed to previous variants7-10. However, people who had received three doses of the mRNA vaccines from Pfizer/BioNTech or Moderna had much higher neutralizing antibody titers7.
To the best of my knowledge, there is not enough data about the efficacy of four doses to draw any conclusions. Still, it is expected that having the fourth dose would increase one’s antibody titer and protect against re-infection. At the same time, not only vaccines but also the natural immunity that is produced by a previous infection will help prevent more serious symptoms, including death. Even though there has been a spike in the number of cases of infection, the intensive care units of hospitals have not been overwhelmed and mortality remains lower than it was before vaccines became available. That is probably due to the ability of vaccines and natural immunity to produce memory cells that will be activated by dendritic cells in the acquired immune system. That is, the human immune system has a fast initial response to infection that is innate and needs no training. It also has a delayed response that does need training by the innate system.
The adaptive immune system uses white blood cells called lymphocytes. The adult human body has about 2 trillion lymphocytes, constituting 20-40 % of all the white blood cells. The peripheral blood contains 20–50 % of them as circulating lymphocytes. The rest of them move within the lymphatic system. Natural killer cells are large and granular. Smaller lymphocytes are T and B cells, produced in the thymus and bone marrow. Memory T cells can recognize bacteria, viruses and cancer cells. Effector memory T cells (TEM) reside in peripheral tissues and migratory cells that can move from the periphery and into the blood. Moreover, TEM cells rapidly recognize and kill infected target cells, thus containing new infections. There is also a network of antibodies in the immune system. They are connected to other antibodies and antigens.
Antibodies are always being made, even in the absence of infection. They help define self. Every day, about 100 precursors of immune cells enter the thymus and undergo several cell divisions to make about hundreds of millions (107 – 108) T cells. Still, the immune systems of very old individuals are characterized by loss of immune cells and reduced diversity of B and T cells. Also, many elderly people in the USA and many other developed countries suffer from chronic low-grade inflammation due to obesity and other factors. As a result, the elderly are at a higher risk of death after being infected by the SARS-CoV-2 virus, especially if they have not been vaccinated and have co-morbidities, such as diabetes.
So, it’s important to note that the reports of immune evasion in people who have been vaccinated or been exposed to the virus only measured the activity of the innate immune system. They did not measure the activity of the acquired immune system. Perhaps the best measures of that are mortality (number of deaths) and the number of people who end up in an ICU. By those measures, the acquired immune systems of many people are healthy enough to prevent death. However, many people suffer lingering morbidities, such as weakness, fatigue and mental difficulties. This is called long Covid12. Most people who get Covid-19 recover completely within a few weeks. However, some people continue to experience symptoms after their initial recovery. This has been called post-Covid-19 syndrome or long Covid-19. They are generally considered to be effects of Covid-19 that persist for more than four weeks after initially testing positive for the SARS-CoV-2 virus. By this time, the patients test negative for the virus. It has been effectively removed from their bodies by their immune systems. Still, they suffer the long-term effects. Even those who had mild versions of the disease are vulnerable. Common signs and symptoms that linger over time include fatigue, shortness of breath or difficulty breathing, cough, joint pain, chest pain, problems with memory, concentration or sleep, muscle pain or headache, fast or pounding heartbeat, loss of smell or taste, depression or anxiety, fever, dizziness when you stand, worsened symptoms after physical or mental activities. Moreover, Covid-19 can sometimes cause prolonged illness, even in young adults and children without underlying chronic medical conditions. As described in my previous article, some also suffer from a rare, but serious disease called multisystem inflammatory syndrome in children, or MIS-C13.
So, simple answers are not available and over-simplified statements can be misleading. It is true that the new BA.5 subvariant can evade neutralization by the innate immune systems of many people. However, elderly people who have received four doses of an mRNA vaccine are probably better protected than those who have not kept their vaccinations up to date. Most people who have not been vaccinated recently are at higher risk of at least being infected. Others who have been previously infected are getting re-infected. Even though the seroprevalence level in the USA reached almost 95% in the USA in December 2021, levels of infection and re-infections surged in early 2022. They are increasing again, due to the BA.5 subvariant.
In the meantime, another potentially dangerous omicron subvariant called BA.2.75 has emerged14,15. The World Health Organization (WHO) has designated it as a Variants of Concern (VOC) Lineage Under Monitoring (LUM) 16. This means that it is an offshoot of a variant that has already been designated a VOC and deserves to be closely watched. BA.2.75 has eight more mutations than BA.5. Many of them could make immune escape even more prevalent. BA.2.75 is another reminder that the coronavirus is continually evolving—and spreading. Still, it is too early to draw any conclusions about transmissibility.
Meanwhile, Pfizer/BioNTech and Moderna have developed and are testing vaccines that target the omicron variant17,18. One of them may be available in August19. For many of us, the new normal will be receiving booster shots twice each year.
1 African Union, Africa Centres for Disease Control and Prevention’s statement regarding the new SARS-COV-2 virus variant B.1.1.529, 25 Nov., 2021.
2 Smith, R.E. Freedom during the Covid-19 pandemic. Humans debate, while viruses mutate freely. Meer, 24 Dec., 2021.
3 Smith, R.E. Omicron subvariants BA.1 and BA.2 have become predominant, causing more infections but less severe symptoms of Covid-19. Meer, 24 March, 2022.
4 Tegally, H. et al. Continued Emergence and Evolution of Omicron in South Africa: New BA.4 and BA.5 lineages. MedRxiv, 2 May, 2022.
5 Kimura, I. et al. Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5. bioRxiv, 26 May, 2022.
6 Centers for Disease Control (CDC) COVID Data Tracker. Variants & Genomic Surveillance. Variant Proportions. 14 July, 2022.
7 Qu, P. et al. Neutralization of the SARS-CoV-2 omicron BA.4/5 and BA.2.12.1 subvariants. New England Journal of Medicine, 15 June, 2022.
8 Hachmann, N.P. et al. Neutralization escape by SARS-CoV-2 omicron subvariants BA.2.12.1, BA.4, and BA.5, New England Journal of Medicine, 5 July, 2022.
9 Tuekprakhon, A. et al. Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum. Cell, 9 June, 2022.
10 Cao, Y. et al. BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Nature, 15 June, 2022.
11 Smith, R.E. Covid-19: Immune response to the SARS-CoV-2 virus. The response to this virus depends in large part on the health of one’s neuroendocrine immune system. Meer, 24 April, 2021.
12 Smith, R.E. Chronic Covid-19 syndrome. The potential dangers of long-term Covid-19. Meer, 24 June, 2021.
13 Smith, R.E. In response to the COVID-19 pandemic. Total Quality Leadership (TQL). Meer, 24 March, 2021.
14 Thacker, T. & Bureau, E.T. BA.2.75 variant of Omicron spreads, but no clustering yet. The Economic Times, 9 July, 2022.
15 Unger, L. & Ghosal, A. A super contagious omicron mutant is worrying scientists. It’s called BA.2.75. Time, 11 July, 2022.
16 WHO, Tracking SARS-CoV-2 variants.
17 Pfizer. Pfizer and BioNTech Announce Omicron-Adapted COVID-19 Vaccine Candidates Demonstrate High Immune Response Against Omicron. 25 June, 2022.
18 Lovelace, B. Moderna says bivalent vaccine appears to work against omicron subvariants BA.4 and BA.5. NBC News, 22 June, 2022.
19 Cerullo, M. Moderna CEO says new COVID-19 variant shot will be ready by August. CBS News, 23 June, 2022.