ABSTRACT
Purpose: The purpose of this study was to evaluate long term humoral and cellular immunity generated following SARS-CoV-2 infection in solid organ transplant recipients (SOTR). Method(s): Patients included had an active graft of an organ transplant as an adult, a positive polymerase chain reaction nasopharyngeal swab for SARS-CoV-2 after transplant, and had not received convalescent plasma, vaccination, or monoclonal antibody for SARS-CoV-2. Whole blood was obtained 6 months (+/- 1 month) after infection. Serology measured IgG and IgM titer to the SARS-CoV-2 spike protein receptor binding domain, reported as signal/ cut-off ratio (s/co). CD4+ and CD8+ T-cell reactivity was measured by Activation Induced Marker assays following stimulation of peripheral blood mononuclear cells with SARS-CoV-2 peptide pools encompassing the SARS-CoV-2 spike protein. Result(s): Of 25 subjects, 19 (76.0%) were hospitalized, 4 (16.0%) developed hypoxia, but none required mechanical ventilation. Biopsy-proven graft rejection occurred in 3 (12.0%), but none had graft loss. At 6 months, 8 (16%) had persistent symptoms and 2 (4.0%) were re-infected within one year. In the immunity study, 22 (88.0%) had reactive IgG testing and 11 (44.0%) had reactive IgM testing. Median IgG titer was 3.68 s/co (range 0.19-36.44) and IgM titer was 0.79 s/co (range 0.02-16.41). Virus-specific CD4+ T-cell reactivity was noted in 23 (92%), but only 10 (40.0%) had reactive CD8+ T-cell testing. Moderate correlation was observed between IgG and IgM titer (r=.51, p= 0.009) and between IgG titer and percent virus-specific CD4+ T-cells (r=.46, p=0.02). CD8+ T-cell reactivity was correlated with greater illness severity (p=0.043). Use of Tacrolimus, mycophenolate, or corticosteroids at time of infection was not associated with T-cell or antibody reactivity. Conclusion(s): In summary, this cohort of SOTR evaluated six months after noncritical COVID-19 illness demonstrated robust IgG and CD4+ T-cell responses, and CD8+ T-cell reactivity was correlated with higher disease severity.
ABSTRACT
Purpose: The purpose of this study was to study our cohort of adult solid organ transplant recipients who had been infected with SARS-CoV-2 to describe the incidence density of SARS-CoV-2 re-infection, as well as the clinical features and convalescent immunity profile. Method(s): Incidence density was calculated as the total cases of re-infection divided by total days after initial diagnosis with active graft. We included those with initial infection diagnosed by polymerase chain reaction before or after transplantation, and cycle threshold values were obtained when possible. Two recipients had immunity evaluated in the weeks prior to re-infection, by measuring IgG antibody titer to the SARS-CoV-2 receptor binding domain and virus-specific CD4+ and CD8+ T-cell reactivity following stimulation with SARS-CoV-2 peptide pools and using activation induced marker assays. Result(s): Out of 210 infected recipients, 5 (2.4%) developed re-infection, including two that had received full mRNA vaccination, but none developed hypoxia. The incidence density was 9.4 (95% confidence interval 3.9-22.6) cases/100,000 patient days. Two cases of re-infection had participated in our immunity study and had convalescent immunity data from a blood draw approximately six months after initial infection and prior to re-infection. Both mounted virus specific CD4 T cell responses prior to re-infection (1.19% and 0.28% of total CD4 T cells) and both had reactive IgG testing (1.30 and 4.99 signal/cut off ratio). Conclusion(s): This suggests that SOT recipients infected with SARS-CoV-2 remain at high risk for re-infection even after generating reactive cellular and humoral immune responses.
ABSTRACT
Purpose: Even though a high efficacy and immunogenicity of COVID-19 vaccines have been reported in the general population, vaccine immunogenicity is suboptimal in SOT recipients and breakthrough SARS-CoV-2 infection has already been reported in this immunocompromised population. Thus, several approaches including booster dose administration was investigated and showed better outcome. However, as a booster, mix and match method has not been investigated enough yet. The aim and objectives of this study is to check the immunogenicity after third dose of the SARSCoV- 2 vaccines either with adenovirus vector vs. mRNA vaccine. Method(s): This is a single center, single blinded (patient blinded), randomized controlled trial comparing BNT 162b2 and JNJ-78436735 as a third dose after completion of two doses of BNTT 162b2 vaccine in SOT recipients. We included adult SOT recipients with functional graft on at least one immunosuppressive medication. Also, the participants should have completed two doses of BNT162b2 vaccination at least 28 days prior to the third dose. As a primary end point, we are going to check the anti-spike protein of SARS-CoV-2 IgG positive rate in one month after vaccination. Result(s): We have finished the enrollment and there were 60 SOT recipients including 39 kidney, 11 liver, 4 lung, 2 heart and 4 combined organ transplant recipients. Already, 58 recipients completed the follow up blood test visit. Median age of the enrolled recipients was 56.7 (IQR 51 - 63) and 22 (37.9%) were female. As a maintenance immunosuppression, 52 (89.7%), 45 (77.5%) and 26 (44.8%) recipients received tacrolimus, mycophenolate and prednisone, respectively. Conclusion(s): Immunogenicity data will be analyzed once the follow up blood test result are finished. Adverse events and the rate of COVID-19 also will be reported.
ABSTRACT
Background: Immune dysfunction characterized by lower antibody (Ab) response to infection or vaccination has been well described among People Living with HIV (PLWH), but due to the novelty of the SARS-CoV-2 virus has not been evaluated among PLWH coinfected with SARS-CoV-2. This study compared the magnitude and longevity of Ab response to SARS-CoV-2 in a group of HIV+ and HIV-individuals infected with SARS-CoV-2 Methods: 17 HIV+COVID+ and 19 HIV-COVID+ participants were recruited from the community as part of the ACTION study and followed longitudinally at day 14, 1 month and 3 months. HIV+ were on effective ART (plasma viral load <500 copies/ml). SARS-CoV-2 infection was confirmed by SARS-COV2 DNA PCR and rapid antibody test. All participants had mild/moderate COVID-19 without hospitalization. Antibody responses (IgG and IgM) were measured using an indirect in house developed ELISA using spike RBD antigen (courtesy, Scott Boyd, Stanford University) and the data are expressed as relative Ab units based on the positive control standard. Results: The median age of HIV+ participants was 55 (26-63) with 23.5% (4/17) females. The median age for HIV-was 38 (27-78) with 57.8% (11/19) females. Time from COVID-19 diagnosis was 26 days for HIV+ and 21 for HIV-. Mean CD4 count for the HIV+ participants was 859.5 ± 287.2 cells/μl. Longitudinal analysis did not show a significant reduction in Ab response at 3 months in either HIV+ or HIV-groups. Levels of SARS-CoV-2 RBD specific IgM and IgG responses did not differ significantly between HIV+ and HIV-at any timepoint although there was a trend of lower IgM and IgG responses at 3 months in both groups compared to entry levels. Age was correlated with IgG response at day 14 (r =0.6, p = 0.02), 1 month (r =0.6, p = 0.014) and 3 month(r =0.87, p = 0.0008) in HIV+ and weakly correlated at day 14 (r =0.46, p = 0.04) in HIV-. Absolute CD4 count was not correlated with IgM and IgG responses in HIV+. Conclusion: The magnitude and persistence of Ab response to SARS-CoV-2 infection in the 3-4 months post-infection does not differ by HIV status. Although extended longitudinal follow-ups are required to gain insights about the longevity of Ab responses in HIV+ individuals, results suggest that immune protection and vaccine responses may not differ by HIV status.