Hybrid immunity retained six months after SARS-CoV-2 exposure

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered the 2019 coronavirus disease (COVID-19) pandemic. Since the start of the pandemic, several SARS-CoV-2 variants have emerged with different transmission rates, virulence and capacity to escape immune responses elicited by either COVID-19 vaccination or natural infection compared to the ancestral variant. .

Study: Hybrid immunity 6 months after exposure to SARS-CoV-2 in subjects 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 COVID-19 cases and deaths.

During this period, the number of daily cases reached about 20,000, with more than 300 reported deaths per day. The subsequent decline in the number of COVID-19 cases occurred after the implementation of pharmaceutical and non-pharmaceutical measures.

Previous studies have shown that COVID-19 vaccination plays an important role in reducing daily infections and hospitalizations due to severe infections. According to the US Centers of Disease Control and Prevention (CDC), COVID-19 vaccination, particularly when using messenger ribonucleic acid (mRNA) vaccines, has significantly reduced the death rate from COVID-19.

Most of the population in Thailand has been vaccinated with inactivated vaccines, and a small percentage have received an mRNA vaccine as a booster vaccine dose.

The emergence of the SARS-CoV-2 Omicron variant in Thailand caused an increase in daily infections reaching nearly 50,000 per day. However, the number of deaths from SARS-CoV-2 infection remained low, at about 120 per day.

Scientists have previously hypothesized that herd immunity would develop after a majority 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 and hesitation about vaccines.

A study in the United Kingdom coined the concept of ‘hybrid immunity’, which refers to the protection offered by COVID-19 vaccination and natural infection. Previous studies have shown that hybrid immunity can protect individuals from symptomatic infection.

About the study

In a new study reviewed in the journal Scientific Reports and currently available on the Research square* preprint server, scientists hypothesize that lower death rates in COVID-19 patients may be due to hybrid immunity, as well as the reduced severity of Omicron infections.

The current study included 79 participants from 15 families who were registered in a database of the home health service in Bangkok between August 1, 2021 and August 31, 2021. In this study cohort, 34 individuals had recovered from COVID-19 at least four weeks prior to enrollment, while the remaining 45 participants were in close contact with COVID-19 patients.

Study findings

T cell responses to Neuromyelitis optica (NMO) antigens were detected by the interferon release assay in 11 of 45 close contacts six months after SARS-CoV-2 exposure. The percentage of asymptomatic COVID-19 was estimated at 24.4%.

The SARS-CoV-2 receptor binding domain (RBD) immunoglobulin G (IgG) antibody levels, as well as T cell responses to the SARS-CoV-2 spike protein, after the second COVID-19 vaccine dose, was associated with similar immunity between COVID -19 patients and close contacts. For example, participants who received COVID-19 booster vaccination with no history of previous COVID-19 also benefited from hybrid immunity.

The antibody response to RBD IgG (Figure 2A) demonstrated the correlation between the levels of antibody and neutralization capacity for the alpha variant of SAR-CoV-2 virus (R = 0.5571, P <0,0001).  De niveaus van RBD IgG bij COVID-19-patiënten en gesloten contacten volgens het aantal vaccinaties worden weergegeven in figuur 2B.  NT = neutraliserend antilichaam, RBD IgG = SARS-CoV-2-receptorbindend domein immunoglobuline G, AU/ml = willekeurige eenheden per milliliter.

The antibody response to RBD IgG (Figure 2A) demonstrated the correlation between the levels of antibody and neutralization capacity for the alpha variant of SAR-CoV-2 virus (R = 0.5571, P < 0.0001). The levels of RBD IgG in COVID-19 patients and closed contacts according to the number of vaccinations are shown in Figure 2B. NT = neutralizing antibody, RBD IgG = SARS-CoV-2 receptor binding domain immunoglobulin G, AU/ml = arbitrary units per milliliter.

A similar level of immunity was observed in individuals who were in close contact with asymptomatic and symptomatic infected individuals.

Previously, no long-term observational data were available regarding the reinfection rate in subjects exposed to SARS-CoV-2. In the current study, none of the participants were reinfected with SARS-CoV-2 during enrollment. Figure 3.

Immune response to SARS-CoV-2 viral antigens compared between close contacts with and without asymptomatic infection, antibody response (RBD IgG) P = 0.1922

Immune response to 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), T cell response to spike protein P = 0.5325 , t=0.6293, df=43 (Figure 3B). RBD IgG = SARS-CoV-2 receptor binding domain immunoglobulin G, AU/ml = arbitrary units per milliliter.

Most of the study participants had received heterogeneous COVID-19 booster vaccination, including viral vector vaccines, inactivated vaccines, and mRNA vaccines. To this end, reduced T cell responses against the spike protein and higher RBD IgG levels were observed after booster vaccination.

After a short period of depletion, T cells can recover three months after receiving a COVID-19 booster dose. This observation is consistent with a previous study that reported a sustained effective immune response after heterogeneous immunization against the Omicron variant.

Previous studies have shown that individuals may have different levels of cellular and humoral immune responses during similar viral infections. Since the majority of study participants received an mRNA vaccine as a booster dose, this could alter T-cell function after vaccination.

Therefore, the authors strongly recommend multiple booster doses of the COVID-19 vaccine only for immunocompromised individuals who exhibit a poor T-cell response. T-cell-based vaccines would also provide an enhanced therapeutic benefit, particularly for these patients.

conclusions

The current study revealed that both antibody and cellular responses determine COVID-19 immunity in society. Taken together, these responses may confer long-term hybrid immunity after booster vaccination against symptomatic and asymptomatic COVID-19.

A major limitation of the current study is its small size, which limits the generalizability of the results. In addition, the immune response was disrupted by vaccination.

*Important announcement

Research Square publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, should guide clinical practice/health-related behavior or be treated as established information.

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