Antibody response to the third dose of inactivated COVID-19 vaccine in people living with HIV (PLWH): A longitudinal cohort.

The immunogenicity induced by the third dose of inactivated coronavirus disease 2019 (COVID-19) vaccines in people living with HIV (PLWH) is unclear, and relevant literature is extremely scarce. It is important to add evidence on the humoral immune response induced by the third dose of inactivated COVID-19 vaccine in PLWH. We collected peripheral venous blood for spike receptor binding domain-protein specific immunoglobulin G (S-RBD-IgG) antibody tests at 28 days after the second dose (T1 ), 180 days after the second dose (T2 ) and 35 days after the third dose (T3 ) of inactivated COVID-19 vaccines in PLWH. The differences in S-RBD-IgG antibody levels and specific seroprevalence among T1 , T2 , and T3 time periods were analyzed, and the effects of age, vaccine brand, and CD4+ T cell count on the levels and specific seroprevalence of S-RBD-IgG antibody induced by the third dose in PLWH were examined. The third dose of inactivated COVID-19 vaccines induced strong S-RBD-IgG antibody responses in PLWH. The levels and specific seroprevalence of S-RBD-IgG antibody were significantly higher than those at 28 and 180 days after the second dose and were not affected by vaccine brand or CD4+ T cell count. Younger PLWH produced higher levels of S-RBD-IgG antibody. The third dose of inactivated COVID-19 vaccine showed good immunogenicity in PLWH. It is necessary to popularize the third dose in the PLWH population, especially PLWH who do not respond to two doses of inactivated COVID-19 vaccines. Meanwhile, the durability of the protection provided by the third dose in PLWH must be continuously monitored.

Willingness to receive the COVID-19 vaccine among HIV positive men who have sex with men in China: a cross-sectional study.

BACKGROUND: People living with HIV(PLWH) are deemed more vulnerable to the SARS-CoV-2 infection than the uninfected population. Vaccination is an effective measure for COVID-19 control, yet, little knowledge exists about the willingness of men who have sex with men (MSM) living with HIV in China to be vaccinated. METHODS: This cross-sectional study evaluated the willingness of MSM living with HIV to receive COVID-19 vaccination in six cities of Guangdong, China, from July to September 2020. Factors associated with willingness to receive COVID-19 vaccination using multivariable logistic regression. RESULTS: In total, we recruited 944 HIV-positive MSM with a mean age of 29.2 ± 7.7 years. Of all participants, 92.4% of them were willing to receive the COVID-19 vaccine. Participants who were separated, divorced, or widowed (adjusted OR: 5.29, 95%CI: 1.02-27.48), had an annual income higher than 9,000 USD (adjusted OR: 1.70, 95%CI: 1.01-2.86), had ever taken an HIV self-test (adjusted OR: 1.78, 95%CI: 1.07-2.95), had ever disclosed sexual orientation to a doctor/nurse (adjusted OR: 3.16, 95%CI: 1.33-7.50), had ever disclosed sexual orientation to others besides their male partners (adjusted OR: 2.18, 95%CI: 1.29-3.69) were more willing to receive the vaccine. Sex with a female partner in the past six months decreased the likelihood of willingness to receive the vaccine (adjusted OR: 0.40, 95%CI: 0.17-0.95). Economic burden, worry that my health condition could not bear the risk of receiving COVID-19 vaccines, and concern that the vaccination would affect the immune status and antiretroviral therapy were the main reasons for unwillingness to receive vaccination. CONCLUSION: Our study showed that HIV-positive MSM had a high willingness to receive the COVID-19 vaccination. Targeted interventions such as health education should be conducted among MSM with HIV infection to enhance COVID-19 vaccine uptake.

Failure to seroconvert after three doses of inactivated COVID-19 vaccines in a patient co-infected with HBV and HIV: A case report.

In the global context of the COVID-19 pandemic, the overall benefits of getting any COVID-19 vaccine approved by the World Health Organization for emergency use outweigh the potential risks, even in people with weakened immune systems, including people living with HIV (PLWH). At present, there are no reports of HIV/hepatitis B virus (HBV) co-infected patients receiving a booster dose of the inactivated COVID-19 vaccine. Here, we describe a patient with HIV/HBV co-infection who did not seroconvert to three doses of the inactivated COVID-19 vaccine.

IgG Antibody Responses and Immune Persistence of Two Doses of BBIBP-CorV Vaccine or CoronaVac Vaccine in People Living with HIV (PLWH) in Shenzhen, China.

The purpose of this study was to preliminarily evaluate the immunogenicity and immune persistence of inactivated SARS-CoV-2 vaccines in PLWH in the real world. We collected blood samples from 132 PLWH aged 18-59 years who were vaccinated with two doses of BBIBP-CorV vaccine (Sinopharm) or CoronaVac vaccine (SinoVac) at 28 ± 7 days and 180 ± 20 days the after second dose, to detect the level of Spike receptor binding domain-protein specific IgG (S-RBD-IgG) by using chemiluminescence. We found that the BBIBP-CorV vaccine or the CoronaVac vaccine induced lower S-RBD-IgG antibody seropositivity rates and levels in PLWH than in healthy controls (HCs). The BBIBP-CorV vaccine or the CoronaVac vaccine induced lower humoral immune responses in PLWH, having lower CD4+T cell counts (<350 cells/µL) compared to PLWH, and having higher CD4+T cell counts (≥350 cells/µL) after a second dose of vaccination. The BBIBP-CorV vaccine or the CoronaVac vaccine induced lower S-RBD-IgG antibody levels in PLWH, having CD4+T cell counts ≥350 cells/µL compared to HCs. No negative effects were observed in terms of the CD4+T cell counts and HIV RNA viral load (VL) of PLWH after vaccination. Ninety-nine PLWH and eighty-three HCs completed a second blood collection for testing; we found a statistically significant decrease in the humoral immune response both in PLWH and HCs from 28 days to 180 days after a second dose of BBIBP-CorV vaccine or CoronaVac vaccine. The S-RBD-IgG antibody induced by the BBIBP-CorV vaccine or the CoronaVac vaccine declined faster in the PLWH population than in the healthy population, and two doses of the BBIBP-CorV vaccine or the CoronaVac vaccine may not be enough to provide PLWH with persistent immunity against SARS-CoV-2. It is necessary for PLWH to be prioritized for a third dose over the healthy population, but the immunogenicity of the third dose of the homologous or heterologous vaccine requires further study.

Three Specific Potential Epitopes That Could Be Recognized by T Cells of Convalescent COVID-19 Patients Were Identified From Spike Protein.

The current coronavirus disease 2019 (COVID-19) vaccines are used to prevent viral infection by inducing neutralizing antibody in the body, but according to the existing experience of severe acute respiratory syndrome coronavirus (SARS) infection, T-cell immunity could provide a longer durable protection period than antibody. The research on SARS-CoV-2-specific T-cell epitope can provide target antigen for the development and evaluation of COVID-19 vaccines, which is conducive to obtain COVID-19 vaccine that can provide long-term protection. For screening specific T-cell epitopes, a SARS-CoV-2 S protein peptide library with a peptide length of 15 amino acids was synthesized. Through flow cytometry to detect percentage of IFN-γ+ T cells after mixed COVID-19 convalescent patients' peripheral blood mononuclear cell with peptide library, seven peptides (P77, P14, P24, P38, P48, P74, and P84) that can be recognized by the T cells of COVID-19 convalescent patients were found. After excluding the nonspecific cross-reactions with unexposed population, three SARS-CoV-2-specific T-cell potential epitopes (P38, P48, and P84) were finally screened with the positive reaction rates between 15.4% and 48.0% in COVID-19 convalescent patients. This study also provided the HLA allele information of peptide-positive-response COVID-19 convalescent patients, thus predicting the population coverage of these three potential epitopes. Some HLA alleles showed higher frequency of occurrence in COVID-19 patients than in total Chinese population but no HLA alleles related to the T-cell peptide response and the severity of COVID-19. This research provides three potential T-cell epitopes that are helpful for the design and efficacy evaluation of COVID-19 vaccines. The HLA information provided by this research supplies reference significance for subsequent research such as finding the relation of HLA genotype with disease susceptibility.

Seropositive Reaction Rates of 9 B-Cell Epitopes of the SARS-CoV-2 Spike Protein and the Relationship between the Epitopes and Neutralizing Antibody.

OBJECTIVE: The aim of the study was to analyze the relationship between serum antibody and neutralizing antibody titers in convalescent coronavirus disease 2019 (COVID-19) patients with different disease severities, and the seropositive reaction rates of 9 reported B-cell epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Serum IgG and total antibody titers of 165 convalescent COVID-19 patients were determined by chemiluminescence, the serum neutralization antibody titers were determined by microneutralization assay, and the S/CO values of 9 peptides were detected by indirect enzyme-linked immunosorbent assay. Correlations between the aforementioned indexes were statistically analyzed, and differences in patients with different diseases severities were evaluated. RESULTS: IgG, total antibody, and neutralizing antibody titers increased with disease severity. The positive rate of the receptor-binding region (RBD) was 100%, and the average positive rate for all the 9 peptides was above 50% in 165 patients. IDf showed the highest rate of positivity (86.06%), with a rate of 95% for the (IDf + IDa) pattern. Moreover, S/CO values of RBD and mix (IDh) were significantly correlated with IgG, total antibody titers, and neutralizing antibody titers (p < 0.001), whereas the S/CO values for other 8 peptides showed no obvious correlation. CONCLUSION: In this study, a large sample was used to confirm that the peptide IDf had a high positive reaction rate for all patients (86.06%) and also had the highest detection rate in asymptomatic patients (86.67%). Only long peptide and mixed peptide showed correlation with neutralizing antibody titers, suggesting that the ability of SARS-CoV-2 antibody to neutralize virus infectivity may require the interaction of multiple sites.

A newly identified linear epitope on non-RBD region of SARS-CoV-2 spike protein improves the serological detection rate of COVID-19 patients.

BACKGROUND: Serological test is helpful in confirming and tracking infectious diseases in large population with the advantage of fast and convenience. Using the specific epitope peptides identified from the whole antigen as the detection antigen is sensitive and relatively economical. The development of epitope peptide-based detection kits for COVID-19 patients requires comprehensive information about epitope peptides. But the data on B cell epitope of SARS-CoV-2 spike protein is still limited. More importantly, there is a lack of serological data on the peptides in the population. In this study, we aimed to identify the B cell epitope peptides of spike protein and detect the reactivity in serum samples, for further providing data support for their subsequent serological applications. RESULTS: Two B cell linear epitopes, P104 and P82, located in non-RBD region of SARS-CoV-2 S protein were identified by indirect ELISA screening of an overlapping peptide library of the S protein with COVID-19 patients' convalescent serum. And the peptides were verified by testing with 165 serum samples. P104 has not been reported previously; P82 is contained in peptide S21P2 reported before. The positive reaction rates of epitope peptides S14P5 and S21P2, the two non-RBD region epitopes identified by Poh et al., and P82 and P104 were 77.0%, 73.9%, 61.2% and 30.3%, respectively, for 165 convalescent sera, including 30 asymptomatic patients. Although P104 had the lowest positive rate for total patients (30.3%), it exhibited slight advantage for detection of asymptomatic infections (36.7%). Combination of epitopes significantly improved the positive reaction rate. Among all combination patterns, (S14P5 + S21P2 + P104) pattern exhibited the highest positive reaction rate for all patients (92.7%), as well as for asymptomatic infections (86.7%), confirming the feasibility of P104 as supplementary antigen for serological detection. In addition, we analyzed the correlation between epitopes with neutralizing antibody, but only S14P5 had a medium positive correlation with neutralizing antibody titre (rs = 0.510, P < 0.01). CONCLUSION: Our research proved that epitopes on non-RBD region are of value in serological detection especially when combination more than one epitope, thus providing serological reaction information about the four epitopes, which has valuable references for their usage.

Viral RNA level, serum antibody responses, and transmission risk in recovered COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study.

Managing recovered COVID-19 patients with recurrent-positive SARS-CoV-2 RNA test results is challenging. We performed a population-based observational study to characterize the viral RNA level and serum antibody responses in recurrent-positive patients and evaluate their viral transmission risk. Of 479 recovered COVID-19 patients, 93 (19%) recurrent-positive patients were identified, characterized by younger age, with a median discharge-to-recurrent-positive length of 8 days. After readmission, recurrent-positive patients exhibited mild (28%) or absent (72%) symptoms, with no disease progression. The viral RNA level in recurrent-positive patients ranged from 1.8 to 5.7 log10 copies/mL (median: 3.2), which was significantly lower than the corresponding values at disease onset. There are generally no significant differences in antibody levels between recurrent-positive and non-recurrent-positive patients, or in recurrent-positive patients over time (before, during, or after recurrent-positive detection). Virus isolation of nine representative specimens returned negative results. Whole genome sequencing of six specimens yielded only genomic fragments. 96 close contacts and 1,200 candidate contacts of 23 recurrent-positive patients showed no clinical symptoms; their viral RNA (1,296/1,296) and antibody (20/20) tests were negative. After full recovery (no longer/never recurrent-positive), 60% (98/162) patients had neutralizing antibody titers of ≥1:32. Our findings suggested that an intermittent, non-stable excretion of low-level viral RNA may result in recurrent-positive occurrence, rather than re-infection. Recurrent-positive patients pose a low transmission risk, a relatively relaxed management of recovered COVID-19 patients is recommended.

Recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients during medical isolation observation.

Recently, the recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients is receiving more attention. Herein we report a cohort study on the follow-up of 182 recovered patients under medical isolation observation. Twenty (10.99%) patients out of the 182 were detected to be SARS-CoV-2 RNA positive (re-positives), although none showed any clinical symptomatic recurrence, indicating that COVID-19 responds well to treatment. Patients aged under 18 years had higher re-positive rates than average, and none of the severely ill patients re-tested positive. There were no significant differences in sex between re-positives and non-re-positives. Notably, most of the re-positives turned negative in the following tests, and all of them carried antibodies against SARS-CoV-2. This indicates that they might not be infectious, although it is still important to perform regular SARS-CoV-2 RNA testing and follow-up for assessment of infectivity. The findings of this study provide information for improving the management of recovered patients, and for differentiating the follow-up of recovered patients with different risk levels.