The cellular response to SARS-CoV-2 vaccination and infection in allogeneic hematopoietic stem cell transplant (HSCT) recipients is not yet clear. In the current study, HSCT recipients prior to and post vaccination were tested for SARS-CoV-2-specific humoral and cellular immunity. Antibodies against spike (S) 1 were assessed by Anti-SARS-CoV-2 IgG ELISA (Euroimmun). Cellular immunity was analyzed by an in house interferon-gamma ELISpot and T-SPOT.COVID (Oxford Immunotec), using altogether seven SARS-CoV-2-specific antigens. In 117 HSCT patients vaccinated twice, SARS-CoV-2 IgG antibodies were significantly higher than in HSCT controls pre vaccination (p < 0.0001). After the second vaccination, we observed a median antibody ratio of 4.7 and 68% positive results, whereas 35 healthy controls reached a median ratio of 9.0 and 100% positivity. ELISpot responses in patients were significantly (p < 0.001) reduced to ≤33% of the controls. After the second vaccination, female HSCT patients and female healthy controls showed significantly higher antibody responses than males (6.0 vs. 2.1 and 9.2 vs. 8.2, respectively; p < 0.05). Cellular immunity was diminished in patients irrespective of sex. In conclusion, especially male HSCT recipients showed impaired antibody responses after SARS-CoV-2 vaccination. Changing the vaccine schedule or composition could help increase vaccine responses.

The novel, highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a pandemic of acute respiratory illness worldwide and remains a huge threat to the healthcare system’s capacity to respond to COVID-19. Elderly and immunocompromised patients are at increased risk for a severe course of COVID-19. These high-risk groups have been identified as developing diminished humoral and cellular immune responses. Notably, SARS-CoV-2 RNA remains detectable in nasopharyngeal swabs of these patients for a prolonged period of time. These factors complicate the clinical management of these vulnerable patient groups. To date, there are no well-defined guidelines for an appropriate duration of isolation for elderly and immunocompromised patients, especially in hospitals or nursing homes. The aim of the present study was to characterize at-risk patient cohorts capable of producing a replication-competent virus over an extended period after symptomatic COVID-19, and to investigate the humoral and cellular immune responses and infectivity to provide a better basis for future clinical management. In our cohort, the rate of positive viral cultures and the sensitivity of SARS-CoV-2 antigen tests correlated with higher viral loads. Elderly patients and patients with diabetes mellitus had adequate cellular and humoral immune responses to SARS-CoV-2 infection, while immunocompromised patients had reduced humoral and cellular immune responses. Our patient cohort was hospitalized for longer compared with previously published cohorts. Longer hospitalization was associated with a high number of nosocomial infections, representing a potential hazard for additional complications to patients. Most importantly, regardless of positive SARS-CoV-2 RNA detection, no virus was culturable beyond a cycle threshold (ct) value of 33 in the majority of samples. Our data clearly indicate that elderly and diabetic patients develop a robust immune response to SARS-CoV-2 and may be safely de-isolated at a ct value of more than 35.

Vulnerable patients such as immunosuppressed or elderly patients are at high risk for a severe course of COVID-19 upon SARS-CoV-2 infection. Immunotherapy with SARS-CoV-2 specific monoclonal antibodies (mAb) or convalescent plasma represents a considerable treatment option to protect these patients from a severe or lethal course of infection. However, monoclonal antibodies are not always available or less effective against emerging SARS-CoV-2 variants. Convalescent plasma is more commonly available and may represent a good treatment alternative in low-income countries. We retrospectively evaluated outcomes in individuals treated with mAbs or convalescent plasma and compared the 30-day overall survival with a patient cohort that received supportive care due to a lack of SARS-CoV-2 specific therapies between March 2020 and April 2021. Our data demonstrate that mAb treatment is highly effective in preventing severe courses of SARS-CoV-2 infection. All patients treated with mAb survived. Treatment with convalescent plasma improved overall survival to 82% compared with 61% in patients without SARS-CoV-2 targeted therapy. Our data indicate that early convalescent plasma treatment may be an option to improve the overall survival of high-risk COVID-19 patients. This is especially true when other antiviral drugs are not available or their efficacy is significantly reduced, which may be the case with emerging SARS-CoV-2 variants.

In kidney transplant (KTX) patients, immune responses after booster vaccination against SARS-CoV-2 are inadequately examined. We analyzed these patients a median of four months after a third/fourth vaccination and compared them to healthy controls. Cellular responses were analyzed by interferon-gamma (IFN-γ) and interleukin-2 (IL-2) ELISpot assays. Neutralizing antibody titers were assessed against SARS-CoV-2 D614G (wild type) and the variants alpha, delta, and omicron by a cell culture-based neutralization assay. Humoral immunity was also determined by a competitive fluorescence assay, using 11 different variants of SARS-CoV-2. Antibody ratios were measured by ELISA. KTX patients showed significantly lower SARS-CoV-2-specific IFN-γ responses after booster vaccination than healthy controls. However, SARS-CoV-2-specific IL-2 responses were comparable to the T cell responses of healthy controls. Cell culture-based neutralizing antibody titers were 1.3-fold higher in healthy controls for D614G, alpha, and delta, and 7.8-fold higher for omicron (p < 0.01). Healthy controls had approximately 2-fold higher concentrations of potential neutralizing antibodies against all 11 variants than KTX patients. However, more than 60% of the KTX patients displayed antibodies to variants of SARS-CoV-2. Thus, KTX patients should be partly protected, due to neutralizing antibodies to variants of SARS-CoV-2 or by cross-reactive T cells, especially those producing IL-2.

While SARS-CoV-2 has transitioned to an endemic phase, infections caused by newly emerged variants continue to result in severe, and sometimes fatal, outcomes or lead to long-term COVID-19 symptoms. Vulnerable populations, such as PLWH, face an elevated risk of severe illness. Emerging variants of SARS-CoV-2, including numerous Omicron subvariants, are increasingly associated with breakthrough infections. Adapting mRNA vaccines to these new variants may offer improved protection against Omicron for vulnerable individuals. In this study, we examined humoral and cellular immune responses before and after administering adapted booster vaccinations to PLWH, alongside a control group of healthy individuals. Four weeks following booster vaccination, both groups exhibited a significant increase in neutralizing antibodies and cellular immune responses. Notably, there was no significant difference in humoral immune response between PLWH and the healthy controls. Immune responses declined rapidly in both groups three months post vaccination. However, PLWH still showed significantly increased neutralizing antibody titers even after three months. These findings demonstrate the efficacy of the adapted vaccination regimen. The results suggest that regular booster immunizations may be necessary to sustain protective immunity.

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.