By: Elsie C. Jimenez
Coronavirus disease 2019 (COVID-19) is an infectious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 has a host membrane-derived lipid bilayer encapsulating the helical capsid containing viral RNA. Proteins, such as, spike glycoprotein (S protein) which mediates interaction with host cell surface receptor, and membrane glycoprotein are embedded in the membrane. Under the electron microscope, the S protein protruding from the viral surface gives the virus a typical halo-like form, thus it was named coronavirus (‘crown’ virus).
The COVID-19 is contracted mainly through close contact with an infected individual. The SARS-CoV-2 spreads mostly by persons who spew out large droplets and small particles called aerosols when they breathe, cough, or sneeze. Although possible, contracting the virus from surfaces appears unusual. While COVID-19 spreads rapidly, most people experience only mild or moderate symptoms. In fact, majority of people who developed COVID-19 had recovered.
Nevertheless, even if many individuals are recovering from the illness, a significant number of deaths has occurred.
Natural immunity
Understanding the immune response to COVID-19 is key to our capability to escape the pandemic. One of the best indicators of immunity is whether a person has antibodies in the blood that recognize distinct constituents of SARS-CoV-2. Memory B and T cells can recognize these constituents indicating previous infection. So far, the immunological measurements that have been done are mostly immunoglobulin G (IgG) antibody levels, some immunoglobulin A (IgA), immunoglobulin M (IgM), and neutralizing antibody levels, and a few memory B and T cell levels. Many patients who have recovered have detectable antibodies for several weeks after the infection. The best marker of immunity is neutralizing antibody that can prevent viral entry into cells. The existence of antibodies does not necessarily predict the existence of memory B or T cells. Individuals differ in the quantity and quality (effectivity in preventing infection) of antibodies, and in the quantity and quality of memory B and T cells they produce after infection.
Although the neutralizing antibody, as well as memory B and T cells, are associated with disease protection, there are no sufficient data to be able to accurately predict a person’s level and duration of protection from SARS-CoV-2. The presence of antibodies may not assure that a person cannot transmit the virus to others. Majority of people who have COVID-19 generate immune response but whether it is effective in preventing reinfection is difficult to ascertain.
Some individuals produce a very effective immune response, so they will not develop the disease and will not transmit the virus to others (referred to as ‘sterilizing’ immunity). Other people produce antibodies and can be protected from the disease, but they may still be carriers of the virus and can infect others (referred to as ‘protective’ immunity).
Older people, as well as those whose immune systems are compromised by autoimmune diseases, immunodeficiency diseases, or by taking some medicines, are unable to make immune
responses as good as those of healthy young people. Reduced immune responses have been observed as well in children compared with adults.
Natural immunity or infection-induced immunity declines over time due to the decrease in the quantity of antibodies and may result in reinfection. When antibodies are missing, immunity can be revived. If a person encounters again the virus, antibody-secreting cells can be regenerated from the memory B and T cells. So, while the presence of antibodies is a good sign of immunity, examining memory B and T cells may give a better correlation of protection.
Reinfection depends on the immunity level a person derives from the first infection and the exposure to social environment. The evidence of reinfection is difficult to obtain but several documented cases have shown that reinfection is possible in a few months after the first infection. Reinfection rates have been linked to antibody levels.
Vaccine-induced immunity
Several COVID-19 vaccines are available to attain immunity to the virus by stimulating an immune response to a foreign body (referred to as antigen), that is, the S protein which the virus normally utilizes to invade human cells. The vaccines are of four types: 1) messenger ribonucleic acid, or mRNA (e.g., Pfizer-BioNTech, Moderna), 2) viral vector (e.g., AstraZeneca-Oxford, Johnson & Johnson), 3) inactivated virus (e.g., Sinovac), and 4) protein subunit (e.g., Novavax). The mRNA vaccine is used to give human cells the instructions to make S protein in large quantity using the cells’ protein machinery. Viral vector vaccine which uses genetically modified adenovirus causing common cold works by giving human cells the genetic instructions to make S protein. The inactivated vaccine utilizes a non-replicating virus whose genetic material has been disabled but the S protein remains intact. Protein subunit vaccine contains fragments of the S protein being introduced into the human cells.
The vaccines as approved by FDA generally appear safe. Although human clinical trials have documented the capability of the vaccines in protecting against COVID-19, there have been reservations whether the vaccines will prevent the transmission of the virus or will have adverse side effects in the long term. No sufficient time has elapsed since the vaccines initially were dispensed in humans and the time for longevity of vaccine-induced immunity to be ascertained, but it has been the focus of vaccine studies. More clarifications on the longevity of immunity, and whether the vaccine prevents the transmission of SARS-CoV-2 to others or simply protects the individual who has been vaccinated from contracting COVID-19 are crucial to exit the pandemic. Also, the longevity of vaccine-induced immunity is a determining factor whether it will be necessary to have a recurrent vaccination program.
The currently approved vaccines, although with varying degrees of efficacy, have been shown to lessen the possibility of developing COVID-19. They appear to prevent mild, moderate, and severe symptoms. But it is not yet known if any of the vaccines can prevent reinfection or whether those given the vaccines can remain contagious. To find out if vaccination affects contagiousness, the occurrence of asymptomatic infection and viral shedding after vaccination are being evaluated by some vaccine teams. So far, studies of SARS-CoV-2 infection, as well as data from vaccine trials, give evidence that robust neutralizing antibody and memory cell responses can protect against COVID-19.
It is likely that vaccines will be efficacious against minor viral mutations. The antibody and memory B and T cell responses that are produced following vaccination are very diverse and so, they recognize different parts of the virus S protein. A modification in one part of the protein might indicate that a few types of antibodies and memory cells will no longer recognize it but there will be a part of the immune response that will remain active. Novavax, for e.g., has reported that the vaccine is efficacious against UK and South Africa variants.
Vaccine teams have shown evidence that an interval between vaccine doses increases immunity. For most currently available vaccines, it is important that people are administered two doses, weeks apart to boost immunity. On the other hand, Johnson & Johnson vaccine protects against moderate to severe disease after a single dose.
Any probable vaccine side effects (e.g., arm pain, muscle ache, headache, fever) are generally mild and short-term. The vaccine dose has been tested to guarantee an individual develops good immunity. The currently available vaccines focus the immune response against the virus S protein (instead of the whole virus) in a stabilized form which aptly maximizes immunity.
The COVID-19 data indicates that immunity will last for at least a year. The emergence of new viral strains stresses the possibility that the current vaccines may become less efficacious over time. So, periodic modification of vaccines may be necessary to protect from mutant strains.
Vaccine companies signify that they are working on next generation vaccines which consider the new variants.
Herd immunity
Herd immunity is attained when transmission of the virus within a population is considerably lessened due to the high percentage of individuals who develop immunity. If enough people become immune, the SARS-CoV-2 is at low or undetectable levels, thereby protecting one who does not get vaccinated, such as, children, adults who are unable to generate a good immune response, and those who are allergic to vaccine constituents. To confer herd immunity, a vaccine needs to considerably decrease the virus transmission. If the vaccine prevents symptoms but has minimal effect on infectivity, it cannot confer herd immunity since vaccinated people, without developing the disease, will still get infected and spread the virus. The important aspects for herd immunity are that the immune response decreases infection and transmission, and that it is long- lasting.
Concluding remarks
Everyone has a responsibility in protecting oneself and others from developing COVID-19. People must wash hands properly, wear face masks and face shields as needed, and observe social distancing. Efforts to prevent SARS-CoV-2 transmission should focus also on improving ventilation. It must be emphasized that individuals have varying degrees of immunity. Until such time that herd immunity is attained, there is a need for effective treatments for those who contract the disease. Knowing the facts about COVID-19 can help prevent people from developing and transmitting the disease. These include the effectiveness of the immune response, and the longevity of vaccine-induced immunity. The natural immunity (or infection-induced immunity) and vaccine-induced immunity should be complementary, with both boosting each other. Since the level of natural immunity or immunity derived from infection cannot be ascertained, it is necessary for most people to get vaccinated.
References:
“Corona virus is in the air – there’s too much focus on surfaces” (Editorial), in Nature 2021 (590:7)
immunology.org/publicinformation
Kumar, Swatantra, Rajni Nyodu, Vimal K. Maurya, and Shailendra K. Saxena, “Morphology, genome organization, replication, and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),” in Coronavirus Disease 2019 (COVID-19) 2020 (23-31)
Ludwig, Stephan, and Alexander Zarbock, “Coronaviruses and SARS-CoV-2: A brief overview,” in Anest Analg 2020 (XXX:1-4)
http://who.int/…/covid1-19/information/recognize-respond
About the Author
The author, Dr. Elsie C. Jimenez, is an emeritus professor of Chemistry at the University of the Philippines Baguio where she has also been conferred the title of University Scientist in 2006-2008. Dr. Jimenez has a Ph.D. in Molecular Biology and Biotechnology and a B.S. in Chemistry both from the University of the Philippines Diliman and an M.S. in Biochemistry from the University of the Philippines Manila.
(The article was first published on April 13, 2021, on the UP Baguio Facebook page.)