Dynamics of Antibody Responses after Asymptomatic and Mild to Moderate SARS-CoV-2 Infections: Real-World Data in a Resource-Limited Country.

The dynamics of humoral immune responses of patients after SARS-CoV-2 infection is unclear. This study prospectively observed changes in anti-receptor binding domain immunoglobulin G (anti-RBD IgG) and neutralizing antibodies against the Wuhan and Delta strains at 1, 3, and 6 months postinfection between October 2021 and May 2022. Demographic data, clinical characteristics, baseline parameters, and blood samples of participants were collected. Of 5059 SARS-CoV-2 infected adult patients, only 600 underwent assessment at least once between 3 and 6 months after symptom onset. Patients were categorized as immunocompetent (n = 566), immunocompromised (n = 14), or reinfected (n = 20). A booster dose of a COVID-19 vaccine was strongly associated with maintained or increased COVID-19 antibody levels. The booster dose was also more strongly associated with antibody responses than the primary vaccination series. Among patients receiving a booster dose of a mRNA vaccine or a heterologous regimen, antibody levels remained steady or even increased for 3 to 6 months after symptom onset compared with inactivated or viral vector vaccines. There was a strong correlation between anti-RBD IgG and neutralizing antibodies against the Delta variant. This study is relevant to resource-limited countries for administering COVID-19 vaccines 3 to 6 months after infection.

Early antiviral and supervisory dexamethasone treatment improve clinical outcomes of nonsevere COVID-19 patients.

This study aimed to evaluate the efficacy of early antiviral treatment in preventing clinical deterioration in asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus 2 infected (COVID-19) patients in home isolation and to share our experiences with the ambulatory management of nonsevere COVID-19 patients. This retrospective study included mild COVID-19 adult patients confirmed by real-time reverse transcription-polymerase chain reaction. They received care via an ambulatory management strategy between July 2021 and November 2021. Demographic data, clinical progression, and outcomes were collected. Both descriptive and inferential statistics were performed to illustrate the cohort's characteristic and outcomes of the study. Univariable and multivariable logistic regression models were employed to investigate the associations between clinical factors and disease progression. A total of 1940 patients in the Siriraj home isolation system met the inclusion criteria. Their mean age was 42.1 ±â€…14.9 years, with 14.2% older than 60 years, 54.3% female, and 7.1% with a body weight ≥ 90 kg. Only 115 patients (5.9%) had deterioration of clinical symptoms. Two-thirds of these could be managed at home by dexamethasone treatment under physician supervision; however, 38 of the 115 patients (2.0% of the study cohort) needed hospitalization. Early favipiravir outpatient treatment (≤ 5 days from onset of symptoms) in nonsevere COVID-19 patients was significantly associated with a lower rate of symptom deterioration than late favipiravir treatment (50 [4.6%] vs 65 [7.5%] patients, respectively; P = .008; odds ratio 1.669; 95% confidence interval, 1.141-2.441). The unfavorable prognostic factors for symptom deterioration were advanced age, body weight ≥ 90 kg, unvaccinated status, higher reverse transcription-polymerase chain reaction cycle threshold, and late favipiravir treatment. The early delivery of essential treatment, including antiviral and supervisory dexamethasone, to ambulatory nonsevere COVID-19 patients yielded favorable outcomes during the COVID-19 pandemic in Thailand.

Evaluation of the Safety and Immunogenicity of Fractional Intradermal COVID-19 Vaccines as a Booster: A Pilot Study.

Intradermal vaccination using fractional dosages of the standard vaccine dose is one strategy to improve access to COVID-19 immunization. We conducted a pilot study in healthy adults in Thailand to evaluate the safety and immunogenicity of intradermal administration of fractional doses of ChAdOx1 (1/5th of standard dosage) or BNT162b2 (1/6th of standard dosage) to individuals previously vaccinated (prime) with two-dose intramuscular CoronaVac, ChAdOx1 or BNT162b2. Following an initial immunogenicity exploratory phase for each vaccine combination group (n = 10), a total of 135 participants (n = 45 per group) were recruited to 3 groups (CoronaVac prime-intradermal BNT162b2 boost, CoronaVac prime-intradermal ChAdOx1 boost and ChAdOx1 prime-intradermal BNT162b2 boost) and their immunogenicity data were compared to a previous cohort who received the same vaccine intramuscularly. Two weeks following booster vaccination, neutralizing antibodies against the delta variant were similar between the participants who received intradermal and intramuscular vaccination. However, neutralizing antibodies against the omicron variant in the intradermal BNT162b2 boost groups were ~6-fold lower, while the levels in the ChAdOx1 boost group were similar compared to their respective vaccine regimen given intramuscularly. The intradermal booster significantly increased spike-specific T cell responses in all three groups from pre-booster levels. Local and systemic adverse reactions were milder in intradermal compared to intramuscular injections. Further studies are needed to evaluate the clinical relevance of these findings and the feasibility of administration of intradermal COVID-19 vaccines.

Early diagnosis by antigen test kit and early treatment by antiviral therapy: An ambulatory management strategy during COVID-19 crisis in Thailand.

This study aimed to assess the clinical characteristics of patients who registered at the Siriraj Favipiravir Clinic and to share our experiences in this comparatively unique clinical setting. This retrospective study included patients who registered at the Siriraj Favipiravir Clinic during August 11, 2021 to September 14, 2021. Included adult patients were those with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) infection confirmed by antigen test kit (ATK) or real-time reverse transcription-polymerase chain reaction, no favipiravir contraindication, no prior COVID-19 treatment, and not receiving care from another medical facility. Demographic data and outcomes were collected and analyzed. Of the 1168 patients (mean age: 44.8 ± 16.4 years, 55.7% female) who registered at the clinic, 117 (10%) did not meet the treatment criteria, and 141 (12%) patients did not pick up their medication. One-third of patients had at least 1 symptom that indicated severe disease. Higher proportion of unvaccinated status (56.7% vs 47.5%, P = .005), higher proportion of persons with risk factors for disease progression (37.7% vs 31.3%, P = .028), and longer duration between the date of clinic registration and the date of positive diagnostic test (3 vs 2 days, P = .004) were significantly more commonly observed in the severe disease group compared to the nonsevere disease group. The duration between symptom onset and the date of clinic registration was significantly longer in the real-time reverse transcription-polymerase chain reaction group than in the ATK group (6 vs 4 days, P < .001). Most patients (90.0%) had completed favipiravir treatment regimen. The improvement and mortality rates were 86.7% and 1.2%, respectively. COVID-19 severity is associated with vaccination status, baseline risk factors, and timing between disease detection and treatment. The use of ATK influences patients to seek treatment significantly earlier in ambulatory setting. Our early diagnosis and antiviral treatment strategy yielded favorable results in an outpatient setting during a COVID-19 outbreak in Thailand.

SARS-CoV-2 Antibody Response against Mild-to-Moderate Breakthrough COVID-19 in Home Isolation Setting in Thailand.

BACKGROUND: In December 2021, Omicron replaced Delta as the dominant coronavirus disease 2019 (COVID-19) variant in Thailand. Both variants embody diverse epidemiological trends and immunogenicity. We investigated whether Delta and Omicron patients' biological and clinical characteristics and immunogenicity differed post-COVID-19 infection. METHODS: This retrospective cohort study investigated the clinical outcomes and laboratory data of 5181 patients with mild-to-moderate COVID-19 (Delta, 2704; Omicron, 2477) under home isolation. We evaluated anti-receptor-binding domain immunoglobulin G (anti-RBD IgG) and surrogate viral neutralizing (sVNT) activity in 495 individuals post-COVID-19 infection during the Delta pandemic. RESULTS: Approximately 84% of all patients received favipiravir. The median cycle threshold (Ct) values were lower for Omicron patients than Delta patients (19 vs. 21; p < 0.001), regardless of vaccination status. Upper respiratory tract symptoms were more frequent with Omicron patients than Delta patients. There were no significant associations between Ct and Omicron symptoms (95% confidence interval 0.98-1.02). A two-dose vaccine regimen reduced hospital readmission by 10% to 30% and death by under 1%. Anti-RBD IgG and sVNT against Delta were higher among older individuals post-COVID-19 infection. Older individuals expressed anti-RBD IgG and sVNT for a more extended period after two-dose vaccination than other age groups. CONCLUSIONS: After a full vaccination course, breakthrough mild-to-moderate Delta and Omicron infections have limited immunogenicity. Prior infections exert reduced protection against later reinfection or infection from novel variants. However, this protection may be sufficient to prevent hospitalization and death, particularly in countries where vaccine supplies are limited.

Comparison of safety and immunogenicity of CoronaVac and ChAdOx1 against the SARS-CoV-2 circulating variants of concern (Alpha, Delta, Beta) in Thai healthcare workers.

Background: Inactivated vaccine (CoronaVac) and chimpanzee adenovirus-vector vaccine (ChAdOx1) have been widely used in resource-limited settings. However, the information on the reactogenicity and immunogenicity of these two vaccines in the same setting are limited. Methods: Healthy health care workers (HCWs) aged 18 years or older were randomly assigned to receive either two doses of CoronaVac at 4 weeks interval or two doses of ChAdOx1 at 10 weeks interval. Self-reported adverse events (AEs) were collected for 7 days following each vaccination. Immunogenicity was determined by IgG antibodies levels against receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S1 subunit) and the 50% plaque reduction neutralization titers against various strains. Results: Of the 360 HCWs, 180 in each vaccine group, the median (interquartile range: IQR) age was 35 (29-44) years old and 84.2% were female. Participants who received ChAdOx1 reported higher frequency of AEs than those received CoronaVac after both the first dose (84.4% vs. 66.1%, P < 0.001) and second dose (75.6% vs. 60.6%, P = 0.002), with more AEs in those younger than 30 years of age for both vaccines. The seroconversion rates were 75.6% and 100% following the first dose of CoronaVac and ChAdOx1, respectively. All participants were seropositive at 2 weeks after the second dose. The anti-SARS-CoV-2 RBD IgG levels induced by CoronaVac was lower than ChAdOX1 with geometric means of 164.4 and 278.5 BAU/mL, respectively (P = 0.0066). Both vaccines induced similar levels of neutralizing antibodies against the Wuhan strain, with the titers of 337.4 and 331.2; however, CoronaVac induced significantly lower GMT against Alpha (23.1 vs. 92.5), Delta (21.2 vs. 69.7), and Beta (10.2 vs. 43.6) variants, respectively. Conclusion: CoronaVac induces lower measurable antibodies against circulating variants but with lower frequency of AEs than ChAdOx1. An earlier boosting to prevent breakthrough infections may be needed.