Convalescent plasma treatment of critically ill intensive care COVID-19 patients.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be life-threatening, and specific antiviral drugs are currently not available. However, first studies indicated that convalescent plasma treatment might improve the clinical outcome of coronavirus disease 2019 (COVID-19) patients. STUDY DESIGN AND METHODS: In the current study, we investigated the efficacy of convalescent plasma treatment in eight COVID-19 patients. All the patients were critically ill, and seven of them were SARS-CoV-2 RNA-positive when starting treatment. SARS-CoV-2-specific antibodies were determined by an enzyme-linked immunosorbent assay detecting immunoglobulin G (IgG) antibodies against the S1 protein (Euroimmun), and the neutralizing titers were determined with a cell-culture-based neutralization assay. Plasma treatment started between 4 and 23 days after the onset of symptoms. The patients were usually treated by three plasma units, each containing 200-280 ml, which was applied at day 1, 3, and 5. RESULTS: Donor sera had on average lower IgG antibody ratios and neutralizing titers than the COVID-19 patients before the onset of treatment (median ratio of 5.8 and neutralizing titer of 1:320 vs. 7.5 and 1:640, respectively). Nevertheless, we observed an increase of antibody ratios in seven and of neutralizing titers in five patients after treatment; which did, however, not correlate with patient survival. Plasma treatment was effective in three patients, but five deceased despite treatment. Patients who deceased had a later treatment onset than survivors and finally died from multiple organ failure. CONCLUSION: Our data indicate that the efficacy of convalescent plasma treatment of critically ill COVID-19 patients who already had developed strong antiviral immune responses and organ complications is limited.

Prospective, Longitudinal Study on Specific Cellular Immune Responses after Vaccination with an Adjuvanted, Recombinant Zoster Vaccine in Kidney Transplant Recipients.

Solid organ transplant recipients have an up to ninefold higher risk of varicella-zoster virus (VZV) reactivation than the general population. Due to lifelong immunosuppressive therapy, vaccination against VZV may be less effective in kidney transplant (KTX) recipients. In the current study, twelve female and 17 male KTX recipients were vaccinated twice with the adjuvanted, recombinant zoster vaccine Shingrix™, which contains the VZV glycoprotein E (gE). Cellular immunity against various VZV antigens was analyzed with interferon-gamma ELISpot. We observed the strongest vaccination-induced changes after stimulation with a gE peptide pool. One month after the second vaccination, median responses were 8.0-fold higher than the responses prior to vaccination (p = 0.0006) and 4.8-fold higher than responses after the first vaccination (p = 0.0007). After the second vaccination, we observed an at least twofold increase in ELISpot responses towards gE peptides in 22 out of 29 patients (76%). Male sex, good kidney function, early time point after transplantation, and treatment with tacrolimus or mycophenolate were correlated significantly with higher VZV-specific cellular immunity, whereas diabetes mellitus was correlated with impaired responses. Thus, our data indicate that vaccination with Shingrix™ significantly augmented cellular, VZV gE-specific immunity in KTX recipients, which was dependent on several covariates.

Long-Term SARS-CoV-2 Specific Immunity Is Affected by the Severity of Initial COVID-19 and Patient Age.

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the greatest medical challenge. Although crucial to the future management of the pandemic, the factors affecting the persistence of long-term SARS-CoV-2 immunity are not well understood. Therefore, we determined the extent of important correlates of SARS-CoV-2 specific protection in 200 unvaccinated convalescents after COVID-19. To investigate the effective memory response against the virus, SARS-CoV-2 specific T cell and humoral immunity (including virus-neutralizing antibodies) was determined over a period of one to eleven months. SARS-CoV-2 specific immune responses were present in 90% of individual patients. Notably, immunosuppressed patients did not have long-term SARS-CoV-2 specific T cell immunity. In our cohort, the severity of the initial illness influenced SARS-CoV-2 specific T cell immune responses and patients' humoral immune responses to Spike (S) protein over the long-term, whereas the patients' age influenced Membrane (M) protein-specific T cell responses. Thus, our study not only demonstrated the long-term persistence of SARS-CoV-2 specific immunity, it also determined COVID-19 severity and patient age as significant factors affecting long-term immunity.