Long-lasting adaptive immune memory specific to SARS-CoV-2 in convalescent coronavirus disease 2019 stable people with HIV.

OBJECTIVE: While the course of natural immunization specific to SARS-CoV-2 has been described among convalescent coronavirus disease 2019 (COVID-19) people without HIV (PWOH), a thorough evaluation of long-term serological and functional T- and B-cell immune memory among people with HIV (PWH) has not been reported. METHODS: Eleven stable PWH developing mild ( n  = 5) and severe ( n  = 6) COVID-19 and 39 matched PWOH individuals with mild (MILD) ( n  = 20) and severe (SEV) ( n  = 19) COVID-19 infection were assessed and compared at 3 and 6 months after infection for SARS-CoV-2-specific serology, polyfunctional cytokine (interferon-γ [IFN-γ], interleukin 2 [IL-2], IFN-γ/IL-2, IL-21) producing T-cell frequencies against four main immunogenic antigens and for circulating SARS-CoV-2-specific immunoglobulin G (IgG)-producing memory B-cell (mBc). RESULTS: In all time points, all SARS-COV-2-specific adaptive immune responses were highly driven by the clinical severity of COVID-19 infection, irrespective of HIV disease. Notably, while a higher proportion of mild PWH showed a higher decay on serological detection between the two time points as compared to PWOH, persistently detectable IgG-producing mBc were still detectable in most patients (4/4 (100%) for SEV PWH, 4/5 (80%) for MILD PWH, 10/13 (76.92%) for SEV PWOH and 15/18 (83.33%) for MILD PWOH). Likewise, SARS-CoV-2-specific IFN-γ-producing T-cell frequencies were detected in both PWH and PWOH, although significantly more pronounced among severe COVID-19 (6/6 (100%) for SEV PWH, 3/5 (60%) for MILD PWH, 18/19 (94.74%) for SEV PWOH and 14/19 (73.68%) for MILD PWOH). CONCLUSIONS: PWH develop a comparable short and long-term natural functional cellular and humoral immune response than PWOH convalescent patients, which are highly influenced by the clinical severity of the COVID-19 infection.

Collapsing Glomerulonephritis in a Kidney Transplant Recipient after mRNA SARS-CoV-2 Vaccination.

With the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), studies are describing cases of glomerulonephritis arising after vaccination. We present the first case of a kidney transplant patient who, after mRNA vaccination against SARS-CoV-2, developed nephrotic proteinuria and renal dysfunction, with a biopsy diagnostic of collapsing glomerulonephritis. No other triggers for this glomerulonephritis were identified. Antibodies against the spike protein were negative, but the patient developed a specific T-cell response. The close time between vaccination and the proteinuria suggests a possible determinant role of vaccination. We should be aware of nephropathies appearing after COVID-19 vaccination in kidney transplant recipients also.

A comprehensive assessment of long-term SARS-CoV-2-specific adaptive immune memory in convalescent COVID-19 Solid Organ Transplant recipients.

Long-term adaptive immune memory has been reported among immunocompetent individuals up to eight months following SARS-CoV-2 infection. However, limited data is available in convalescent patients with a solid organ transplant. To investigate this, we performed a thorough evaluation of adaptive immune memory at different compartments (serological, memory B cells and cytokine [IFN-γ, IL-2, IFN-γ/IL12 and IL-21] producing T cells) specific to SARS-CoV-2 by ELISA and FluoroSpot-based assays in 102 convalescent patients (53 with a solid organ transplants (38 kidney, 5 liver, 5 lung and 5 heart transplant) and 49 immunocompetent controls) with different clinical COVID-19 severity (severe, mild and asymptomatic) beyond six months after infection. While similar detectable memory responses at different immune compartments were detected between those with a solid organ transplant and immunocompetent individuals, these responses were predominantly driven by distinct COVID-19 clinical severities (97.6%, 80.5% and 42.1%, all significantly different, were seropositive; 84% vs 75% vs 35.7%, all significantly different, showed IgG-producing memory B cells and 82.5%, 86.9% and 31.6%, displayed IFN-γ producing T cells; in severe, mild and asymptomatic convalescent patients, respectively). Notably, patients with a solid organ transplant with longer time after transplantation did more likely show detectable long-lasting immune memory, regardless of COVID-19 severity. Thus, our study shows that patients with a solid organ transplant are capable of maintaining long-lasting peripheral immune memory after COVID-19 infection; mainly determined by the degree of infection severity.

Immunosuppression minimization in kidney transplant recipients hospitalized for COVID-19.

BACKGROUND: Immunosuppressed patients such as kidney transplant recipients (KTs) have increased mortality risk in the setting of coronavirus disease 2019 (COVID-19). The role and management of chronic immunosuppressive therapies during COVID-19 must be characterized. METHODS: Herein, we report the follow-up of a cohort of 47 KTs admitted at two Spanish Kidney Transplant Units, who survived COVID-19. The impact of the management of immunosuppression during COVID-19 on graft function and immunologic events was evaluated. RESULTS: At least one immunosuppressive agent was withdrawn in 83% of patients, with antimetabolites being the most frequent. Steroids were generally not stopped and the dose was even increased in 15% of patients as part of the treatment of COVID-19. Although immunosuppressive drugs were suspended during a median time of 17 days, no rejection episodes or de novo donor-specific antibodies were observed up to 3 months after discharge, and no significant changes occurred in calculated panel reactive antibodies. Acute graft dysfunction was common (55%) and the severity was related to tacrolimus trough levels, which were higher in patients receiving antivirals. At the end of follow-up, all patients recovered baseline kidney function. CONCLUSIONS: Our observational study suggests that immunosuppression in KTs hospitalized due to COVID-19 could be safely minimized.

SARS-CoV-2-specific serological and functional T cell immune responses during acute and early COVID-19 convalescence in solid organ transplant patients.

The description of protective humoral and T cell immune responses specific against SARS-CoV-2 has been reported among immunocompetent (IC) individuals developing COVID-19 infection. However, its characterization and determinants of poorer outcomes among the at-risk solid organ transplant (SOT) patient population have not been thoroughly investigated. Cytokine-producing T cell responses, such as IFN-γ, IL-2, IFN-γ/IL-2, IL-6, IL-21, and IL-5, against main immunogenic SARS-CoV-2 antigens and IgM/IgG serological immunity were tracked in SOT (n = 28) during acute infection and at two consecutive time points over the following 40 days of convalescence and were compared to matched IC (n = 16) patients admitted with similar moderate/severe COVID-19. We describe the development of a robust serological and functional T cell immune responses against SARS-CoV-2 among SOT patients, similar to IC patients during early convalescence. However, at the infection onset, SOT displayed lower IgG seroconversion rates (77% vs. 100%; p = .044), despite no differences on IgG titers, and a trend toward decreased SARS-CoV-2-reactive T cell frequencies, especially against the membrane protein (7 [0-34] vs. 113 [15-245], p = .011, 2 [0-9] vs. 45 [5-74], p = .009, and 0 [0-2] vs. 13 [1-24], p = .020, IFN-γ, IL-2, and IFN-γ/IL-2 spots, respectively). In summary, our data suggest that despite a certain initial delay, SOT population achieve comparable functional immune responses than the general population after moderate/severe COVID-19.

Clinical characteristics and risk factors for severe COVID-19 in hospitalized kidney transplant recipients: A multicentric cohort study.

Kidney transplant recipients might be at higher risk for severe coronavirus disease 2019 (COVID-19). However, risk factors for relevant outcomes remain uncertain in this population. This is a multicentric kidney transplant cohort including 104 hospitalized patients between March 4 and April 17, 2020. Risk factors for death and acute respiratory distress syndrome (ARDS) were investigated, and clinical and laboratory data were analyzed. The mean age was 60 years. Forty-seven patients (54.8%) developed ARDS. Obesity was associated to ARDS development (OR 2.63; P = .04). Significant age differences were not found among patients developing and not developing ARDS (61.3 vs 57.8 years, P = .16). Seventy-six (73%) patients were discharged, and 28 (27%) died. Death was more common among the elderly (55 and 70.8 years, P < .001) and those with preexisting pulmonary disease (OR 2.89, P = .009). At admission, higher baseline lactate dehydrogenase (257 vs 358 IU/mL, P = .001) or ARDS conferred higher risk of death (HR 2.09, P = .044). In our cohort, ARDS was equally present among young and old kidney recipients. However, the elderly might be at higher risk of death, along with those showing higher baseline LDH at admission.