Increased risk of false-positive HIV ELISA results after COVID-19.

OBJECTIVE: From the first-generation options available in 1985, tests to detect HIV-1 specific antibodies have increased its sensitivity and specificity. HIV-1 and SARS-CoV-2 surface glycoproteins present a certain degree of homology and shared epitope motifs, which results of relevance as both pandemics coexist. Here, we aimed to evaluate the rate of false-positive HIV serology results among individuals with COVID-19 diagnosis and in vaccinated individuals. DESIGN: A retrospective analysis of the samples stored at the Infectious Disease Biobank in Argentina from donors with previous COVID-19 diagnosis or anti-SARS-CoV-2 vaccination. METHODS: Plasma samples were analyzed using Genscreen Ultra HIV Ag-Ab. In those with a positive result, the following assays were also performed: ELISA lateral flow Determine Early Detect; RecomLine HIV-1 & HIV-2 IgG and Abbott m2000 RealTime PCR for HIV-1 viral load quantification. In all samples, the presence of anti-SARS-CoV-2 IgG antibodies was evaluated by ELISA using the COVIDAR kit. Statistical analysis was done using Pearson's and Fisher's exact chi-squared test; Mann-Whitney and Kruskal-Wallis tests. RESULTS: Globally, the false-positive HIV ELISA rate was 1.3% [95% confidence interval (95% CI) 0.66-2.22; χ2  = 4.68, P  = 0.03, when compared with the expected 0.4% false-positive rate]. It increased to 1.4% (95% CI 0.70-2.24, χ2  = 5.16, P  = 0.02) when only samples from individuals with previous COVID-19 diagnosis, and to 1.8% (95% CI 0.91-3.06, χ2  = 7.99, P  = 0.005) when only individuals with detectable IgG SARS-CoV-2 antibodies were considered. CONCLUSION: This higher occurrence of HIV false-positive results among individuals with detectable antibodies against Spike SARS-CoV-2 protein should be dispersed among virology testing settings, health providers, and authorities.

SARS-CoV-2-Specific IgG and IgA response in maternal blood and breastmilk of vaccinated naïve and convalescent lactating participants.

Background: Recent studies have shown the presence of SARS-CoV-2-specific antibodies in the milk of breastfeeding mothers vaccinated with mRNA and convalescent. However, limited information is available in lactating women receiving other vaccine platforms used in developing countries, such as the inactivated SARS-CoV-2 vaccine BBIBP-CorV (Sinopharm) and the non-replicating adenovirus vaccines Sputnik V (Gamaleya Institute) and ChAdOx1-S (Oxford AstraZeneca). Methods: Here, we evaluated anti-SARS-CoV-2 IgG and IgA levels in both serum and milk samples using a longitudinal and a cross-sectional cohort of 208 breastfeeding vaccinated women from Argentina with or without previous SARS-CoV-2 infection. Results: The analysis showed that IgA levels remain constant in serum and milk of breastfeeding mothers between the first and second doses of vector-based vaccines (Sputnik V and ChAdOx1-S). After the second dose, anti-spike IgA was found positive in 100% of the serum samples and in 66% of breastmilk samples. In addition, no significant differences in milk IgA levels were observed in participants receiving BBIBP-CorV, Sputnik V or ChAdOx1-S. IgG levels in milk increased after the second dose of vector-based vaccines. Paired longitudinal samples taken at 45 and 120 days after the second dose showed a decrease in milk IgG levels over time. Study of IgA levels in serum and milk of vaccinated naïve of infection and vaccinated-convalescent breastfeeding participants showed significantly higher levels in vaccinated-convalescent than in participants without previous infection. Conclusion: This study is relevant to understand the protection against SARS-CoV-2 by passive immunity in newborns and children who are not yet eligible to receive vaccination.

Immune Response to SARS-CoV-2 Third Vaccine in Patients With Rheumatoid Arthritis Who Had No Seroconversion After Primary 2-Dose Regimen With Inactivated or Vector-Based Vaccines.

OBJECTIVE: The aim of this study was to assess the immune response after a third dose of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA) with undetectable antibody titers after the primary regimen of 2 doses. METHODS: Patients with RA with no seroconversion after 2 doses of SARS-CoV-2 vaccine and who received a third dose of either an mRNA or vector-based vaccine were included. Anti-SARS-CoV-2 IgG antibodies, neutralizing activity, and T cell responses were assessed after the third dose. RESULTS: A total of 21 nonresponder patients were included. At the time of vaccination, 29% were receiving glucocorticoids and 85% biologic disease-modifying antirheumatic drugs (including 6 taking abatacept [ABA] and 4 taking rituximab [RTX]). The majority (95%) received the BNT162b2 vaccine and only one of them received the ChAdOx1 nCoV-19 vaccine. After the third dose, 91% of the patients presented detectable anti-SARS-CoV-2 IgG and 76% showed neutralizing activity. Compared to other treatments, ABA and RTX were associated with the absence of neutralizing activity in 4 out of 5 (80%) patients and lower titers of neutralizing antibodies (median 3, IQR 0-20 vs 8, IQR 4-128; P = 0.20). Specific T cell response was detected in 41% of all patients after the second dose, increasing to 71% after the third dose. The use of ABA was associated with a lower frequency of T cell response (33% vs 87%, P = 0.03). CONCLUSION: In this RA cohort, 91% of patients who failed to seroconvert after 2 doses of SARS-CoV-2 vaccine presented detectable anti-SARS-CoV-2 IgG after a third dose. The use of ABA was associated with a lower frequency of specific T cell response.

Antibody response against SARS-CoV-2 variants of concern in children infected with pre-Omicron variants: An observational cohort study.

BACKGROUND: Despite that pediatric COVID-19 is usually asymptomatic or mild, SARS-CoV-2 infection typically results in the development of an antibody response. Contradictory observations have been reported when the antibody response of children and adults were compared in terms of strength, specificity and perdurability. METHODS: This observational study includes three cohorts infected with SARS-CoV-2 between March 2020-July 2021: unvaccinated infected children (n=115), unvaccinated infected adults (n=62), and vaccinated infected children (n=76). Plasma anti-spike IgG antibodies and neutralising activity against Wuhan, Delta and Omicron variants after 7-17 months post-infection were analysed. FINDINGS: More than 95% of unvaccinated infected children and adults remained seropositive when evaluated at 382-491 and 386-420 days after infection, respectively. Anti-spike IgG titers and plasma neutralising activity against Wuhan, Delta and Omicron variants were higher in children compared to adults. No differences were found when unvaccinated infected children were stratified by age, gender or presence/absence of symptoms in the acute phase of SARS-CoV-2 infection, but a slight decrease in the antibody response was observed in those with comorbidities. Vaccination of previously infected children with two doses of the inactivated BBIBP-CorV or the mRNA vaccines, BNT162b2 and/or mRNA-1273, further increased anti-spike IgG titers and neutralising activity against Wuhan, Delta and Omicron variants. INTERPRETATION: Unvaccinated infected children mount a more potent and sustained antibody response compared with adults, which is significantly increased after vaccination. Further studies including not only the analysis of the immune response but also the effectiveness to prevent reinfections by the different Omicron lineages are required to optimise vaccination strategy in children. FUNDING: National Agency for Scientific and Technological Promotion from Argentina (PICTO-COVID-SECUELAS-00007 and PMO-BID-PICT2018-2548).

Platelets modulate CD4+ T-cell function in COVID-19 through a PD-L1 dependent mechanism.

Severe COVID-19 is associated with a systemic inflammatory response and progressive CD4+ T-cell lymphopenia and dysfunction. We evaluated whether platelets might contribute to CD4+ T-cell dysfunction in COVID-19. We observed a high frequency of CD4+ T cell-platelet aggregates in COVID-19 inpatients that inversely correlated with lymphocyte counts. Platelets from COVID-19 inpatients but not from healthy donors (HD) inhibited the upregulation of CD25 expression and tumour necrosis factor (TNF)-α production by CD4+ T cells. In addition, interferon (IFN)-γ production was increased by platelets from HD but not from COVID-19 inpatients. A high expression of PD-L1 was found in platelets from COVID-19 patients to be inversely correlated with IFN-γ production by activated CD4+ T cells cocultured with platelets. We also found that a PD-L1-blocking antibody significantly restored platelets' ability to stimulate IFN-γ production by CD4+ T cells. Our study suggests that platelets might contribute to disease progression in COVID-19 not only by promoting thrombotic and inflammatory events, but also by affecting CD4+ T cells functionality.

Longitudinal Study after Sputnik V Vaccination Shows Durable SARS-CoV-2 Neutralizing Antibodies and Reduced Viral Variant Escape to Neutralization over Time.

Recent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we examined longitudinal antibody responses and viral neutralizing capacity to the B.1 lineage virus (Wuhan related), to variants of concern (VOC; Alpha, Beta, Gamma, and Delta), and to a local variant of interest (VOI; Lambda) in volunteers receiving the Sputnik V vaccine in Argentina. Longitudinal serum samples (N = 536) collected from 118 volunteers obtained between January and October 2021 were used. The analysis indicates that while anti-spike IgG levels significantly wane over time, the neutralizing capacity for the Wuhan-related lineages of SARS-CoV-2 and VOC is maintained within 6 months of vaccination. In addition, an improved antibody cross-neutralizing ability for circulating variants of concern (Beta and Gamma) was observed over time postvaccination. The viral variants that displayed higher escape to neutralizing antibodies with respect to the original virus (Beta and Gamma variants) were the ones showing the largest increase in susceptibility to neutralization over time after vaccination. Our observations indicate that serum neutralizing antibodies are maintained for at least 6 months and show a reduction of VOC escape to neutralizing antibodies over time after vaccination. IMPORTANCE Vaccines have been produced in record time for SARS-CoV-2, offering the possibility of halting the global pandemic. However, inequalities in vaccine accessibility in different regions of the world create a need to increase international cooperation. Sputnik V is a recombinant adenovirus-based vaccine that has been widely used in Argentina and other developing countries, but limited information is available about its elicited immune responses. Here, we examined longitudinal antibody levels and viral neutralizing capacity elicited by Sputnik V vaccination. Using a cohort of 118 volunteers, we found that while anti-spike antibodies wane over time, the neutralizing capacity to viral variants of concern and local variants of interest is maintained within 4 months of vaccination. In addition, we observed an increased cross-neutralization activity over time for the Beta and Gamma variants. This study provides valuable information about the immune response generated by a vaccine platform used in many parts of the world.

Dynamics of SARS-CoV-2-specific antibodies among COVID19 biobank donors in Argentina.

Biobanks are instrumental for accelerating research. Early in SARS-CoV-2 pandemic, the Argentinean Biobank of Infectious Diseases (BBEI) initiated the COVID19 collection and started its characterization. Blood samples from subjects with confirmed SARS-CoV-2 infection either admitted to health institutions or outpatients, were enrolled. Highly exposed seronegative individuals, were also enrolled. Longitudinal samples were obtained in a subset of donors, including persons who donated plasma for therapeutic purposes (plasma donors). SARS-CoV-2-specific IgM and IgG levels, IgG titers and IgG viral neutralization capacity were determined. Out of 825 donors, 57.1% were females and median age was 41 years (IQR 32-53 years). Donors were segregated as acute or convalescent donors, and mild versus moderate/severe disease donors. Seventy-eight percent showed seroconversion to SARS-CoV-2 specific antibodies. Specific IgM and IgG showed comparable positivity rates in acute donors. IgM detectability rate declined in convalescent donors while IgG detectability remained elevated in early (74,8%) and late (83%) convalescent donors. Among donors with follow-up samples, IgG levels seemed to decline more rapidly in plasma donors. IgG levels were higher with age, disease severity, number of symptoms, and more durable in moderate/severe disease donors. Levels and titers of anti-spike/RBD IgG strongly correlated with neutralization activity against WT virus. The BBEI-COVID19 collection serves a dual role in this SARS-CoV-2 global crisis. First, it feeds researchers and developers transferring samples and data to fuel research projects. Second, it generates highly needed local data to understand and frame the regional dynamics of the infection.

Sputnik V vaccine elicits seroconversion and neutralizing capacity to SARS-CoV-2 after a single dose.

Massive vaccination offers great promise for halting the global COVID-19 pandemic. However, the limited supply and uneven vaccine distribution create an urgent need to optimize vaccination strategies. We evaluate SARS-CoV-2-specific antibody responses after Sputnik V vaccination of healthcare workers in Argentina, measuring IgG anti-spike titers and neutralizing capacity after one and two doses in a cohort of naive or previously infected volunteers. By 21 days after receiving the first dose of the vaccine, 94% of naive participants develop spike-specific IgG antibodies. A single Sputnik V dose elicits higher antibody levels and virus-neutralizing capacity in previously infected individuals than in naive ones receiving the full two-dose schedule. The high seroconversion rate after a single dose in naive participants suggests a benefit of delaying administration of the second dose to increase the number of people vaccinated. The data presented provide information for guiding public health decisions in light of the current global health emergency.