The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the coronavirus disease 2019 (COVID-19) pandemic. Since the beginning of the pandemic, several variants of SARS-CoV-2 have emerged with different rates of transmission, virulence, and ability to escape immune responses elicited by vaccination against COVID-19 or natural infection compared to the ancestral variant.
Study: Hybrid immunity at 6 months after exposure to SARS-CoV-2 in individuals from the community treatment program. Image credit: Cinefootage Visuals / Shutterstock.com
background
The SARS-CoV-2 Delta variant was the dominant circulating strain in Thailand in mid-August 2021. The spread of this variant significantly increased the number of cases and deaths from COVID-19.
During this period, the number of daily cases reached 20,000, with more than 300 deaths each day. The subsequent decline in cases of COVID-19 occurred as a result of the implementation of pharmaceutical and non-pharmaceutical measures.
Previous studies have indicated that vaccination against COVID-19 plays an important role in reducing daily infections and hospitalizations for severe infection. According to the US Centers for Disease Control and Prevention (CDC), vaccination against COVID-19, especially when messenger ribonucleic acid (mRNA)-based vaccines are used, has significantly reduced the death rate of COVID-19 .
The majority of the population in Thailand has been vaccinated with inactivated vaccines, with a small percentage receiving an mRNA vaccine as a booster dose.
The emergence of the Omicron SARS-CoV-2 variant in Thailand led to an increase in daily infections reaching almost 50,000 per day. However, the number of deaths due to SARS-CoV-2 infection remained low, at around 120 each day.
Scientists have previously hypothesized that herd immunity would develop after most of the population was vaccinated or recovered from COVID-19. However, the herd immunity threshold could not be reached due to the emergence of new variants, as well as doubt about the vaccine.
A study from the United Kingdom coined the concept of “hybrid immunity,” which refers to the protection afforded by vaccination against COVID-19 and natural infection. Previous studies have indicated that hybrid immunity can protect people from symptomatic infection.
About the study
In a new study under review in the journal Scientific Reports and currently available on the Research Square preprint server*, scientists hypothesize that lower death rates in patients with COVID-19 may be due to hybrid immunity, as well as to reducing the severity of Omicron infections.
The current study included 79 participants from 15 families registered in a Bangkok Home Health Service database between August 1, 2021 and August 31, 2021. In this study cohort , 34 people had recovered from COVID-19 at least four weeks before enrollment. , while the remaining 45 participants were in close contact with patients with COVID-19.
Results of the study
T cell responses against Neuromyelitis optica (NMO) antigens were detected by interferon release assay in 11 of 45 close contacts six months after exposure to SARS-CoV-2. The rate of asymptomatic COVID-19 was estimated to be 24.4%.
SARS-CoV-2 receptor binding domain (RBD) immunoglobulin G (IgG) antibody levels, as well as T cell responses against the SARS-CoV-2 spike protein, after the second dose of the COVID-19 vaccine was associated with comparable immunity between patients with COVID-19 and close contacts. Thus, participants who received the COVID-19 booster vaccine without any prior history of COVID-19 also benefited from hybrid immunity.
The antibody response to RBD IgG (Figure 2A) demonstrated the correlation between antibody levels and neutralization capacity with the alpha variant of the SAR-CoV-2 virus (R = 0.5571, P < 0.0001 ). Figure 2B shows the levels of IgG RBD in patients with COVID-19 and closed contacts according to the number of vaccinations. NT = neutralizing antibody, RBD IgG = SARS-CoV-2 immunoglobulin G receptor binding domain, AU/ml = arbitrary units per milliliter.
A similar level of immunity was observed among people who were in close contact with asymptomatic and symptomatic infected people.
Previously, long-term observational data were not available related to the rate of reinfection in individuals who were exposed to SARS-CoV-2. In the present study, none of the participants were reinfected with SARS-CoV-2 during enrollment. Figure 3.
Immune response against SARS-CoV-2 viral antigens compared between close contacts with and without asymptomatic infection, antibody response (RBD IgG) P = 0.1922 t = 1.325, df = 43 (Figure 3A), response of T cells against spike protein P = 0.5325 , t=0.6293, df=43 (Figure 3B). RBD IgG = SARS-CoV-2 immunoglobulin G receptor binding domain, AU/ml = arbitrary units per milliliter.
The majority of study participants had received a heterogeneous COVID-19 booster vaccine that included viral vector vaccines, inactivated vaccines, and mRNA vaccines. To this end, reduced T-cell responses against the spike protein and higher levels of IgG RBD were observed after booster vaccination.
After a short period of depletion, T cells can recover three months after receiving a booster dose of COVID-19. This observation aligns with a previous study that reported a retained effective immune response after heterogeneous immunization against the Omicron variant.
Previous studies have revealed that people can have different levels of cellular and humoral immune responses during similar viral infections. Because most study participants received an mRNA vaccine as a booster dose, it could alter T-cell function after vaccination.
Therefore, the authors strongly recommend multiple booster doses of the COVID-19 vaccine only for immunocompromised individuals with poor T-cell responses. T-cell-based vaccines would also provide enhanced therapeutic benefit, particularly for these patients.
Conclusions
The current study revealed that both antibody and cellular responses define immunity to COVID-19 in society. Together, these responses may confer long-term hybrid immunity after booster vaccination against symptomatic and asymptomatic COVID-19.
An important limitation of the current study is its small size, which limits the generalizability of its results. In addition, the immune response was confounded by vaccination.
*Important news
Research Square publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice or health-related behavior, or be treated as established information.