GVN Experts Address What You Need to Know About Variants and Vaccines
Yes, although this is rare, since the current vaccines are effective against the Delta variant. Yet reinfections (i.e., breakthrough infections) can occur. The US CDC has recently evaluated breakthrough infections that cause hospitalization or fatality. As of August 2, 2021, more than 164 million people in the United States had been fully vaccinated against COVID-19. The CDC investigation found 7,525 patients with COVID-19 vaccine breakthrough infection who were hospitalized or died. However, it is important to emphasize that most vaccinated people who are re-infected only show mild symptoms. In fact, vaccination confers an eightfold reduction in the risk of getting infected in the first place; a 25-fold reduction in risk of getting hospitalized; and a 25-fold reduction in the risk for death. Furthermore, a study estimated that COVID-19 vaccinations prevented nearly 140,000 deaths in the U.S. by May 2021.
The Delta variant can replicate in vaccinated people, thus allowing transmission of the virus to others. Vaccinated people have shown to have similar levels of viral loads in nasal swabs compared to unvaccinated people. However, viral loads decline faster in vaccinated people than unvaccinated people, thus leading to better clinical outcomes. This suggests that prevention strategies, including universal masking in indoor public settings, are still required to mitigate the Delta variant and to protect the public.
Yes – you can get COVID-19 again, but it is rare.
Natural immunity acquired after COVID-19 infection will last for several months and at least eight months. Also, there is mounting evidence for a persistent cellular immune protection after such infection. A recent study showed that memory B cells continue to mature and strengthen for at least 12 months after the initial infection. It indicates that your immune cells can produce antibodies against the virus. These studies also suggest that vaccine induced immunity is stronger and far more persistent than natural infection induced immunity. Consistent with this, the number of well documented cases of reinfection has remained very low.
However, re-infection with a variant, which is different from the original strain, appears to be occurring in some cases (see previous section). With the emergence of fast-spreading variants, vaccination will certainly boost immunity and provide protection for individuals recovered from COVID-19.
It is still uncertain how long vaccination will be protective against COVID-19. Recent studies showed that the levels of neutralizing antibodies decrease over time, but memory cells can be persistent. In fact, even though there is a decline in anti-COVID-19 antibody titers from 6 months after the second dose of COVID-19 mRNA vaccines, they still provide effective protection against severe disease and mortality even against the current variants, including the Delta variant. Since duration of protection will differ from one vaccine to another and from one individual’s immune response to another, this information will be obtained when the results of the ongoing prospective studies become available.
Breakthrough infection happens in some fully vaccinated people with the widespread Delta variant. However, COVID-19 vaccines provide protection from hospitalization and mortality. With the emergence and spread of other variants, some vaccinated people (i.e., elderly people and immunocompromised people) might need a booster dose of vaccine to prolong protection against the original coronavirus strain and newly emerging variants. Specifically, to mitigate the spread of the Delta variant, Israel is offering a third shot of the Pfizer-BioNTech Covid-19 vaccine to people over 40 years old. Germany and other Western countries plan to offer a third shot from September. The US FDA approved a third dose of the Pfizer vaccine to immunocompromised people, people over 65 years old, or at high risk for severe COVID-19. The third dose of vaccination is recommended 8 months after the second dose.
Yes – one shot vaccination. Many different studies agree that the antibody response to the first mRNA vaccine dose in individuals recovered from COVID-19 is equal to, or even exceeds, the titers found in naïve individuals after the second dose. These studies suggest that one dose of mRNA vaccine might be sufficient for previously infected people.
Although natural infection can induce protective immunity, the level of acquired immunity could be different depending on the individual’s immune system and disease severity. Importantly, the duration of protective immunity is unclear. Therefore, it is highly recommended for those previously infected to get vaccinated. Vaccination stimulates a “memory” effect and induces good antibody response. This can provide a robust and lasting immunity.
Results from vaccinating people with both the AstraZeneca and Pfizer COVID-19 vaccines showed that this mix-and-match vaccination produced a potent immune response against the SARS-CoV-2 virus. The Pfizer vaccine boosted antibody responses remarkably in one-dose AstraZeneca vaccinees.
Because of safety concerns, several European countries are recommending that some or all people who were given a first dose of AstraZeneca vaccine get another vaccine for their second dose.
COVID-19 vaccines are safe. This was evaluated in tens of thousands of participants in clinical trials and went through the Food and Drug Administration’s (FDA) rigorous review process. Now, at least four billion doses have been administered. All the approved vaccines met the agency’s scientific standards for safety, effectiveness, and manufacturing quality.
The vaccination campaign has extended worldwide. As more people get vaccinated, some rare cases of blood clots have been reported after receiving the AstraZeneca vaccine or Johnson and Johnson vaccine. More specific information can be found at https://gvn.org/covid-19/vaccine-safety/. The World Health Organization (WHO), the European Medicines Agency (EMA), and the UK Regulatory Agency have stated that the benefits of vaccination still greatly outweighed the risks.
The CDC has received a handful of reports of myocarditis and pericarditis in adolescents and young adults after COVID-19 vaccination. There were “relatively few” cases, and they may be entirely unrelated to vaccination. Most cases appear to be mild, and follow-up of cases is ongoing. The agency is currently reviewing these cases. The known and potential benefits of COVID-19 vaccination outweigh the known and potential risks, including the possible risk of myocarditis or pericarditis.
Although monitoring the safety of these vaccines continues, serious side effects that could cause a long-term health problem are extremely unlikely following COVID-19 vaccination. Millions of people have received COVID-19 vaccines, yet no long-term side effects have been detected.
There is no formal contra-indication to vaccinating pregnant women. COVID-19 in pregnant women can lead to severe consequences for the mother and the fetus. Thus, regulatory agencies recommend to make the decision based on the risk of exposure to the virus. A recent surveillance study showed the safety of mRNA Covid-19 vaccines (Pfizer and Moderna) in pregnant persons. However, a long-term effect of vaccines on pregnancy needs to be continuously evaluated.
For the AstraZeneca vaccine, clinical trials have shown that vaccine efficacy was 82.4% in the case of a 12-week interval between the two doses, as compared with 54.9% for a less than 6-week interval. This supports the UK’s strategy for vaccinating as many as people as quickly as possible with a single dose to maximize limited supply. However, more validation studies will be necessary.
Moderna and Pfizer (mRNA-based vaccines) recommend their standard protocols, 4 weeks apart and 3 weeks apart, respectively. Scientists for the Pfizer vaccine suggested having the second dose of immunization within 6 weeks after the first immunization (a grace period). US CDC recommends following the standard protocol for each vaccine but waiting up to 42 days between doses can be tolerated. According to the results from a small-scale UK trial, the Pfizer vaccine generates a significantly more robust antibody response in older people after delaying the second dose to 12 weeks after the first compared to the standard protocol. Further study will be required for verification.
CDC recommends everyone 12 years and older should get a COVID-19 vaccination to help protect against COVID-19. The Pfizer vaccine has been found to be safe and effective in adolescents 12-to 15 years old. Although fewer children have been infected with COVID-19 compared to adults, children can still be infected with the virus, get sick, and spread the virus to others. Also, in a recent study, around 4% of infected children showed persistent clinical symptoms for at least four weeks. Widespread vaccination, including children, is critical to help end the pandemic. Vaccination also allows children to participate in various indoor and outdoor activities safely.
GVN Perspective Today
Merck and Pfizer will allow their oral COVID-19 drugs to be made and sold inexpensively in low-income countries. This will allow many more countries to benefit from the new treatments for COVID-19 and generate a larger global supply.
Mutations refer to the change in the genomic information (composed of DNA or RNA) which synthetizes the various components of a virus. Viruses are constantly changing through mutations of their genome. Most of these mutations will remain silent because they do not provide any advantage to the virus for its dissemination. However, some mutations provide an advantage to the virus, and thus are adapted for better fitness. Indeed, these genetic variations lead to the emergence of variants, which may have different characteristics (virus’ ability to spread, to cause disease, or to escape the body’s immune response).
WHO and CDC classified variants into variants of concern and variants of interest.
- A Variant of Concern is one for which there is evidence of an increase in transmissibility, detrimental change in COVID-19 epidemiology, more severe disease (e.g., increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.
- A Variant of Interest is one with specific genetic markers that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity. The variants are the cause of an increased proportion of cases, or unique outbreak clusters with limited prevalence or expansion globally.
Mutations arise as a natural by-product of viral replication. Like other RNA viruses, SARS-CoV-2 makes mistakes when it copies its RNA genome. These mutations occur over time and SARS-CoV-2 keeps mutating (evolving) to adapt to the host environment. Some of these mutations have been documented emerging in people who are immunosuppressed and who therefore mount a sub-optimal response to the virus, or in people who have received antibodies from another person, as part of a treatment called convalescent serum.
The variants are spreading the same way as the original virus. The variants spread by person-to-person transmission routes. These include direct transmission (cough, sneeze, droplet inhalation transmission) and contact transmission (contact with oral, nasal and eye mucous membranes and to the latter by a contaminated surface).
Epidemiology data have indicated that the variants of concern (Alpha, Beta, Gamma, and Delta) can spread faster than previously known SARS-CoV-2. Specifically, the Alpha variant has shown 30-50% enhanced transmissibility. Further, the Delta variant is quickly becoming the dominant virus by outpacing the Alpha variant globally. A recent study suggests that the Delta variant could be more than twice as transmissible as the original strain of SARS-CoV-2. In fact, in one study from China showed individuals infected with this variant also had viral loads up to 1,260 times higher than those in people infected with the original virus. Epidemiological studies suggest that the Delta variant is enhancing disease severity and mortality and even is causing hospitalization of young adults.
Epidemiology studies have shown reinfection of previously recovered individuals from COVID-19 with certain variants. Yet this is clearly a rare condition. Age can have an impact on reinfection with COVID-19. According to the WHO, amongst those above 65 years, the level of protection against reinfection was estimated to be at 50%. In contrast, among younger people, level of protection against reinfection was nearly 89%.
Particularly, the Beta and Gamma variants are known to be immune escape mutants by evading antibodies from previous infections, thus causing reinfection of individuals who recovered from COVID-19. The Delta variant does seem to have an advantage over previously circulating versions of the virus, especially in individuals whose immunity is waning a while after previous infection or vaccination.
Most countries recommend isolation of people with COVID-19 for 10 days. This is because infectious virus is rarely detected after 8 days. There is no evidence that infectious virus persists for longer with the variants.
Yet, some patients with severe COVID-19 have shown a prolonged duration of virus shedding, up to 20 days after symptom onset. Virus shedding does not mean that you are infectious, as prolonged shedding is usually associated with very low levels of virus.
Currently, duration of contagiousness for patients infected by the variants has not been clearly tested. However, it is very likely that, like previous SARS-CoV-2, individuals infected with a variant will no longer be contagious after 8 days.
Monoclonal antibodies to the viral protein have been shown to efficiently block infection of the human cells by the virus. Recent clinical studies have demonstrated their immediate efficacy to treat early stages of the viral infection. In fact, they have even suggested that using such antibodies might allow prevention of COVID-19 in at risk individuals. However, the cost and the IV administration route do presently limit their use.
Regarding their efficacy against variants, it is important to understand that in contrast with vaccines, such monoclonal antibodies are by definition targeting a single component of the viral envelope. Thus, any mutation at this site would abolish the effect of such monoclonal antibodies. This has recently led to the use of a combination of several monoclonal antibodies targeting different components of the viral envelope (such as the casirivimab and imdevimab antibody cocktail). Recent evidence would suggest the efficacy of such an approach against the Alpha and Beta variants.
No. Current COVID-19 tests cannot detect if a variant is present or not, although some adjusted PCR-based assays have been proposed. This can only be done by genomic sequencing analysis. Thus, genetic surveillance will be key to monitor the circulation of these variants.
Vaccines and Variants
Vaccines will generate what is called a “polyclonal antibody response”, which means that the vaccine generates antibodies to many components of the viral proteins which limit the impact of specific mutations. Depending on the vaccine, they can also generate T-cells, which may be very important to ensuring long term protection, preventing severe disease, and possibly containing variant spread.
In vitro laboratory testing showed that currently available RNA-based vaccines (Pfizer/BioNtech and Moderna) have retained efficacy against the Alpha (B.1.1.7) variant. In contrast, the in vitro testing has shown that the capacity of the antibodies generated by currently available vaccines to neutralize the Beta, Gamma, and Delta variants was decreased. However, the in vivo clinical studies have confirmed that the RNA-based vaccines show sufficient protection against the variants.
In the U.K. trial, efficacy of 2-dose Pfizer vaccine was 87.9% against the Delta variant and 93.4% against the Alpha variant; 2-dose AstraZeneca showed 59.8% efficacy against the Delta variant and 66.1% against the Alpha variant.
According to the data from clinical studies, the efficacy of the Novavax vaccine was 90% in the UK with circulation of the Alpha variant and 60% in South Africa with circulation of the Delta variant. The efficacy of the Johnson & Johnson vaccine was 72% in the US and 57% in South Africa.
Breakthrough infection rarely occurred. However, when looking at the risk of severe disease and hospitalization, the current vaccines seem to offer protection against developing severe COVID-19.
If we are able to achieve mass vaccination, we will see fewer variants.
Indeed, achieving herd immunity by combining natural infection and vaccination will mitigate the spread of virus. There is much uncertainty as to what percentage of the population would need to be immunized, but reaching 80% of the population would likely be safe.
Variants arise because RNA viruses make mistakes every time they replicate. If the virus is given the opportunity to infect many people, this greatly increases the chance of a variant appearing. As vaccination will reduce the total number of infected people, it will therefore reduce transmission and the appearance of variants will reduce significantly.