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Coronavirus disease 2019 (COVID-19) is a contagious illness worldwide. While guidelines for the treatment of COVID-19 have been established, the understanding of the relationship among neutralizing antibodies, cytokines, and the combined use of antiviral medications, steroid drugs, and convalescent plasma therapy remains limited. Here, we investigated the connection between the immunological response and the efficacy of convalescent plasma therapy in COVID-19 patients with moderate-to-severe pneumonia. The study included a retrospective analysis of 49 patients aged 35 to 57. We conducted clinical assessments to determine antibody levels, biochemical markers, and cytokine levels. Among the patients, 48 (98%) were discharged, while one died. We observed significantly higher levels of anti-nucleocapsid, anti-spike, and neutralizing antibodies on days 3, 7, and 14 after the transfusion compared to before treatment. Serum CRP and D-dimer levels varied significantly across these four time points. Moreover, convalescent plasma therapy demonstrated an immunoregulatory effect on cytokine parameters, with significant differences in IFN-β, IL-6, IL-10, and IFN-α levels observed at different sampling times. Evaluating the cytokine signature, along with standard clinical and laboratory parameters, may help to identify the onset of a cytokine storm in COVID-19 patients and determine the appropriate indication for anti-cytokine treatment.

To compare the reactogenicity and immunogenicity between the two-dose mRNA COVID-19 vaccine regimen and one or two doses of inactivated vaccine followed by an mRNA vaccine regimen in healthy children between 5 and 11 years of age, a prospective cohort study was performed at King Chulalongkorn Memorial Hospital in Thailand between March to June 2022. Healthy children between 5 and 11 years of age were enrolled and received the two-dose mRNA COVID-19 vaccine (BNT162b2) regimen or the inactivated (CoronaVac) vaccine followed by the BNT162b2 vaccine regimen. In addition, healthy children who received two doses of BBIBP-CorV between 1 and 3 months prior were enrolled to receive a heterologous BNT162b2 as a third dose (booster). Reactogenicity was assessed by a self-reported online questionnaire. Immunogenicity analysis was performed to determine binding antibodies to wild-type SARS-CoV-2. Neutralizing antibodies to Omicron variants (BA.2 and BA.5) were tested using the focus reduction neutralization test. Overall, 166 eligible children were enrolled. Local and systemic adverse events which occurred within 7 days after vaccination were mild to moderate and well-tolerated. The two-dose BNT162b2, CoronaVac followed by BNT162b2, and two-dose BBIBP-CorV followed by BNT162b2 groups elicited similar levels of anti-receptor-binding domain (RBD) IgG. However, the two-dose BNT162b2 and two-dose BBIBP-CorV followed by BNT162b2 groups elicited higher neutralizing activities against the Omicron BA.2 and BA.5 variant than the CoronaVac followed by BNT162b2 group. The CoronaVac followed by BNT162b2 group elicited low neutralizing activities against the Omicron BA.2 and BA.5 variant. A third dose (booster) mRNA vaccine should be prioritized for this group., (© 2023 Wiley Periodicals LLC.)

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can be asymptomatic in young children. Therefore, the true rate of infection is likely underestimated. Few data are available on the rate of infections in young children, and studies on SARS-CoV-2 seroprevalence among children during the omicron wave are limited. We assessed the SARS-CoV-2 infection-induced seroprevalence among children and estimated the associated risk factors for seropositivity., Methods: A longitudinal serological survey was conducted from January 2021 through December 2022. The inclusion criteria were healthy children between 5 and 7 years old and their parents or legal guardians provided written informed consent. Samples were tested for anti-nucleocapsid (N) IgG and anti-receptor binding domain (RBD) IgG using a chemiluminescent microparticle immunoassay (CMIA), and total anti-RBD immunoglobulin (Ig) was detected using an electrochemiluminescence immunoassay (ECLIA). The vaccination and SARS-CoV-2 infection history were collected., Results: In all, 457 serum samples were obtained from 241 annually followed-up children in this longitudinal serological survey. Of these, 201 participants provided samples at two serial time points-during the pre-omicron and omicron-dominant wave. Overall, seroprevalence induced by SARS-CoV-2 infection increased from 9.1% (22/241) during the pre-omicron to 48.8% (98/201) during the omicron wave. Amongst seropositive individuals, the infection-induced seropositivity was lower in vaccinated participants with two doses of BNT162b2 than in the unvaccinated participants (26.4% vs. 56%; OR, 0.28; 95%CI: 0.14-0.58). Nevertheless, the ratio of seropositive cases per recalled infection was 1.63 during the omicron dominant wave. The overall seroprevalence induced by infection, vaccination, and hybrid immunity was 77.1% (155/201) between January and December 2022., Conclusions: We report an increase in infection-induced seroprevalence among children during the omicron wave. These findings highlight that a seroprevalence survey can help determine the true rate of infection, particularly in asymptomatic infection, and optimize public health policies and vaccine strategies in the pediatric population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Suntronwong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To report the safety and immunogenicity profile of a protein subunit vaccine (Covovax TM ) given as a third (booster) dose to individuals primed with different primary vaccine regimens., Methods: A third dose was administered to individuals with an interval range of 3-10 months after the second dose. The four groups were classified according to their primary vaccine regimens, including two-dose BBIBP-CorV, AZD1222, BNT162b2, and CoronaVac/AZD1222. Immunogenicity analysis was performed to determine binding antibodies, neutralizing activity, and the T-cell responses., Results: Overall, 210 individuals were enrolled and boosted with the Covovax TM vaccine. The reactogenicity was mild to moderate. Most participants elicited a high level of binding and neutralizing antibody against Wild-type and Omicron variants after the booster dose. In participants who were antinucleocapsid immunoglobulin G-negative from all groups, a booster dose could elicit neutralizing activity to Wild-type and Omicron variants by more than 95% and 70% inhibition at 28 days, respectively. The Covovax TM vaccine could elicit a cell-mediated immune response., Conclusion: The protein subunit vaccine (Covovax TM ) can be proposed as a booster dose after two different priming dose regimens. It has strong immunogenicity and good safety profiles., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In light of intermittent supply shortages of individual vaccines and evidence of rare but serious adverse events after vaccination, heterologous regimens for COVID-19 vaccines have gained significant interest. This study aims to assess the reactogenicity and immunogenicity of the heterologous adenoviral vector (ChAdOx1-S, AstraZeneca; hereafter referred to as AZ) and the inactivated vaccine regimen (CoronaVac; hereafter referred to as CV) in healthy Thai adults immunized between June and September 2021. Our study showed that adverse events following homologous CV-CV and AZ-AZ, and heterologous CV-AZ and AZ-CV combinations, were mild and well tolerated overall. Receptor-binding domain (RBD)-specific antibody responses and neutralizing activities against wild-type and variants of concern after two-dose vaccination were higher in the heterologous CV-AZ and homologous AZ-AZ groups compared to the CV-CV and AZ-CV groups. Conversely, the spike-specific IgA response was detected only in the CV-AZ group after two doses of vaccination. The total interferon gamma response was detected in both the CV-AZ and AZ-CV groups after the two-dose vaccination. Given the shorter completion time of two doses, heterologous CoronaVac followed by ChAdOx1-S can be considered as an alternative regimen to homologous efficacy-proven ChAdOx1-S in countries with circulating variants. Additional studies on the efficacy and durability of immune responses induced by heterologous vaccine regimens are warranted.

The coronavirus 2019 omicron variant has surged rapidly and raises concerns about immune evasion even in individuals with complete vaccination, because it harbors mutations. Here we examine the capability of booster vaccination following CoronaVac/AZD1222 prime to induce neutralizing antibodies (NAbs) against omicron (BA.1 and BA.2) and T-cell responses. A total of 167 participants primed with heterologous CoronaVac/AZD1222 for 4-5 months were enrolled, to receive AZD1222, BNT162b2, or mRNA-1273 as a third dose. Reactogenicity was recorded. Immunogenicity analyses of severe acute respiratory syndrome coronavirus 2-binding antibodies were measured using enzyme-linked immunosorbent assay. The NAb titers against omicron BA.1 and BA.2 were determined using the focus reduction neutralization test (FRNT50) and total interferon-γ responses were measured to observe the T-cell activation. A substantial loss in neutralizing potency to omicron variant was found at 4-5 months after receiving the heterologous CoronaVac/AZD1222. Following booster vaccination, a significant increase in binding antibodies and neutralizing activities toward delta and omicron variants was observed. Neutralization to omicron BA.1 and BA.2 were comparable, showing the highest titers after boosted mRNA-1273 followed by BNT162b2 and AZD1222. In addition, individuals boosted with messenger RNA (mRNA) vaccines develop a T-cell response to spike protein, whereas those boosted with AZD1222 did not. Reactogenicity was mild to moderate without serious adverse events. Our findings demonstrated that mRNA booster vaccination is able to overcome waning immunity to provide antibodies that neutralize omicron BA.1 and BA.2, as well as a T-cell response., (© 2022 Wiley Periodicals LLC.)

Background: The use of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac) against SARS-CoV-2 is implemented worldwide. However, waning immunity and breakthrough infections have been observed. Therefore, we hypothesized that the heterologous booster might improve the protection against the delta and omicron variants., Methods: A total of 224 individuals who completed the 2-dose CoronaVac for 6 months were included. We studied reactogenicity and immunogenicity after a heterologous booster with the inactivated vaccine (BBIBP), the viral vector vaccine (AZD1222), and the messenger ribonucleic acid (mRNA) vaccine (both BNT162B2 and mRNA-1273). We also determined immunogenicity at 3- and 6-month boosting intervals., Results: The solicited adverse events were mild to moderate and well tolerated. Total receptor binding domain (RBD) immunoglobulin (Ig), anti-RBD IgG, focus reduction neutralization test (FRNT50) against delta and omicron variants, and T-cell response were highest in the mRNA-1273 group followed by the BNT162b2, AZD1222, and BBIBP groups, respectively. We also witnessed a higher total Ig anti-RBD in the long-interval than in the short-interval group., Conclusions: All 4 booster vaccines significantly increased binding and neutralizing antibodies in individuals immunized with 2 doses of CoronaVac. The present evidence may benefit vaccine strategies to thwart variants of concern, including the omicron variant., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The coronavirus disease 2019 (COVID-19) pandemic has been a serious healthcare problem worldwide since December 2019. The third dose of heterologous vaccine was recently approved by World Health Organization. The present study compared the reactogenicity and immunogenicity of the reduced and standard third booster dose of the BNT162b2 and mRNA-1273 vaccine in adults who previously received the two-dose CoronaVac vaccine. Results showed that headache, joint pain, and diarrhea were more frequent in the 15 μg- than the 30 μg-BNT162b2 groups, whereas joint pain and chilling were more frequent in the 100 μg- than the 50 μg-mRNA-1273 groups. No significant differences in immunogenicity were detected. These findings demonstrate that the reduced dose of the mRNA vaccines elicited antibody responses against the SARS-CoV-2 delta and omicron variants that were comparable to the standard dose. The reduced dose could be used to increase vaccine coverage in situations of limited global vaccine supply., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Sittisak Honsawek and Yong Poovorawan reports administrative support was provided by Chulalongkorn University Faculty of Medicine. Sitthichai Kanokudom reports financial support was provided by the Second Century Fund (C2F). Yong Poovorawan reports administrative support and equipment, drugs, or supplies were provided by the Center of Excellence in Clinical Virology, Chulalongkorn University, and King Chulalongkorn Memorial Hospital. Yong Poovorawan reports equipment, drugs, or supplies was provided by National Research Council of Thailand (NRCT). Yong Poovorawan reports equipment, drugs, or supplies was provided by Health Systems Research Institute (HSRI).]., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: The SARS-CoV-2 Omicron variant presents numerous mutations potentially able to evade neutralizing antibodies (NAbs) elicited by COVID-19 vaccines. Therefore, this study aimed to provide evidence on a heterologous booster strategy to overcome the waning immunity against Omicron variants., Methods: Participants who completed the Oxford/AstraZeneca (hereafter AZD1222) vaccine dose for 5-7 months were enrolled. The reactogenicity and persistence of immunogenicity in both humoral and cellular response after a homologous or heterologous booster with the AZD1222 and messenger RNA (mRNA) vaccines (BNT162b2, full, or half-dose mRNA-1273) administered 6 months after primary vaccination were determined., Results: A total of 229 individuals enrolled, and waning of immunity was observed 5-7 months after the AZD1222-primed vaccinations. Total receptor-binding domain (RBD) immunoglobulin (Ig) levels, anti-RBD IgG, and focus reduction neutralization test against Omicron BA.1 and BA.2 variants and T cell response peaked at 14-28 days after booster vaccination. Both the full and half dose of mRNA-1273 induced the highest response, followed by BNT162b2 and AZD1222. At 90 days, the persistence of immunogenicity was observed among all mRNA-boosted individuals. Adverse events were acceptable for all vaccines., Conclusion: A heterologous mRNA booster provided a significantly superior boost of binding and NAbs levels against the Omicron variant compared with a homologous booster in individuals with AZD1222-primed vaccinations., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study examined the neutralizing activity and receptor-binding domain (RBD) antibody levels against wild-type and omicron BA.1 and BA.2 variants in individuals who received three doses of COVID-19 vaccination. The relationship between the anti-RBD IgG against wild-type and live virus neutralizing antibody titers against omicron BA.1 and BA.2 variants was examined. In total, 310 sera samples from individuals after booster vaccination (third-dose) were tested for specific IgG wild-type SARS-CoV-2 RBD and the omicron BA.1 surrogate virus neutralization test (sVNT). The live virus neutralization assay against omicron BA.1 and BA.2 was performed using the foci-reduction neutralization test (FRNT50). The anti-RBD IgG strongly correlated with FRNT50 titers against BA.1 and BA.2. Non-linear regression showed that anti-RBD IgG at the cut-off value ≥148 BAU/mL and ≥138 BAU/mL were related to the threshold for FRNT50 titers ≥20 against BA.1 and BA.2, respectively. A moderate correlation was observed between the sVNT and FRNT50 titers. At FRNT50 titers ≥20, the predicted sVNT for BA.1 and BA.2 was ≥10.57% and ≥11.52%, respectively. The study identified anti-RBD IgG and sVNT levels that predict detectable neutralizing antibodies against omicron variants. Assessment and monitoring of protective immunity support vaccine policies and will help identify optimal timing for booster vaccination.

Coronavirus disease 2019 (COVID-19) booster vaccination is being comprehensively evaluated globally due to waning immunity and the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Therefore, this study aimed to evaluate antibody responses in individuals vaccinated with two doses of the BBIBP-CorV vaccine and to explore the boosting effect of the different vaccine platforms in BBIBP-CorV-primed healthy adults, including a viral vector vaccine (AZD122) and mRNA vaccines (BNT162b2 and mRNA-1273). The results showed that in the BBIBP-CorV prime group, the total receptor-binding domain (RBD) immunoglobulin (Ig) and anti-RBD IgG levels waned significantly at three months after receiving the second dose. However, after the booster, RBD-specific binding antibody levels increased. Neutralizing antibody measured by a surrogate neutralization test showed inhibition over 90% against the SARS-CoV-2 delta variant but less than 70% against the omicron variant after the third dose on day 28. All booster vaccines could induce the total IFN-ɣ T-cell response. The reactogenicity was acceptable and well-tolerated without serious adverse events. This study supports the administration of the third dose with either a viral vector or mRNA vaccine for BBIBP-CorV-primed individuals to stimulate antibody and T-cell responses.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of immunity in vaccinated individuals is resulting in increased numbers of SARS-CoV-2 breakthrough infections. This study investigated binding antibody responses and neutralizing activities against SARS-CoV-2 variants, in patients with COVID-19 who had been fully vaccinated with CoronaVac ( n = 77), individuals who had been fully vaccinated with CoronaVac but had not contracted COVID-19 ( n = 170), and individuals who had received AZD1222 as a third vaccination ( n = 210). Breakthrough infection was generally detected approximately 88 days after the second CoronaVac vaccination (interquartile range 68-100 days). Blood samples were collected at a median of 34 days after infection. Binding antibody levels in sera from patients with breakthrough infection were significantly higher than those in individuals who had received AZD1222 as a third vaccination. However, neutralizing activities against wild-type and variants, including alpha (B.1.1.7), beta (B.1.351), and delta (B.1.617.2), were comparable in patients with breakthrough infections and individuals who received a third vaccination with AZD1222, which exceeds 90%. Omicron (B.1.1.529) was neutralized less effectively by serum from breakthrough infection patients, with a 6.3-fold reduction compared to delta variants. The study suggests that breakthrough infection after two doses of an inactivated vaccine can induce neutralizing antibodies against omicron. Further investigation is needed to assess the long-term persistence of antibodies against the omicron variant.

In June 2021, Thailand was hit by the delta variant of SARS-CoV-2 resulting in the biggest wave of COVID-19. Due to the widespread delta variant, more than 600 healthcare workers had COVID-19 despite completion of two-dose CoronaVac. The Ministry of Public Health recommended that healthcare workers received a third dose of AZD1222 to increase level of protection against SARS-CoV-2. However, immune response after the AZD1222 booster in individuals who completed the two-dose CoronaVac vaccine are limited. In this study, sera from those who received a booster of AZD1222 in June-July 2021 were tested for SARS-CoV-2 spike receptor-binding-domain (RBD) IgG, anti-RBD total immunoglobulins and anti-spike protein 1 (S1) IgA. The neutralizing activities in a subset of serum samples were tested against the wild type and variants of concern (B.1.1.7, B.1.617.2, and B.1.351) using an enzyme-linked immunosorbent assay-based surrogate virus neutralization test. Participants who received the booster of AZD1222 possessed higher levels of spike RBD-specific IgG, total immunoglobulins, and anti-S1 IgA than the two-dose vaccinees (p < 0.001). They also elicited higher neutralizing activity against the wild type and all variants of concern than the recipients of the two-dose vaccines. This study demonstrated a high immunogenicity of the AZD1222 booster in individuals who completed the two-dose inactivated vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic has become a severe healthcare problem worldwide since the first outbreak in late December 2019. Currently, the COVID-19 vaccine has been used in many countries, but it is still unable to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, despite patients receiving full vaccination doses. Therefore, we aimed to appraise the booster effect of the different platforms of vaccines, including inactivated vaccine (BBIBP), viral vector vaccine (AZD122), and mRNA vaccine (BNT162b2), in healthy adults who received the full dose of inactivated vaccine (CoronaVac). The booster dose was safe with no serious adverse events. Moreover, the immunogenicity indicated that the booster dose with viral vector and mRNA vaccine achieved a significant proportion of Ig anti-receptor binding domain (RBD), IgG anti-RBD, and IgA anti-S1 booster response. In contrast, inactivated vaccine achieved a lower booster response than others. Consequently, the neutralization activity of vaccinated serum had a high inhibition of over 90% against SARS-CoV-2 wild-type and their variants (B.1.1.7-alpha, B.1.351-beta, and B.1.617.2-delta). In addition, IgG anti-nucleocapsid was observed only among the group that received the BBIBP booster. Our study found a significant increase in levels of IFN-ɣ secreting T-cell response after the additional viral vector or mRNA booster vaccination. This study showed that administration with either viral vector (AZD1222) or mRNA (BNT162b2) boosters in individuals with a history of two doses of inactivated vaccine (CoronaVac) obtained great immunogenicity with acceptable adverse events.