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.

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.

Zusammenfassung: Patienten nach einer Nierentransplantation (NTx) sind besonders anfällig für Infektionen, da ihre Immunantwort durch immunsuppressive Therapien stark beeinträchtigt wird. Infektionen erhöhen nicht nur das Risiko für Morbidität und Mortalität, sondern können auch die Funktion des Nierentransplantats beeinträchtigen und Abstoßungsreaktionen auslösen. Daher ist die Infektionsprävention für die wachsende Anzahl an Transplantationsempfängern von höchster Bedeutung. Das Risiko einer Infektion und die Möglichkeit, Infektionen durch Impfungen zu verhindern, hängen direkt vom „net state of immunosuppression“ des einzelnen Patienten ab. Impfantworten und Sicherheitsprofile können bei Transplantationspatienten erheblich von denen der Allgemeinbevölkerung abweichen, was unterschiedliche Impfstrategien und Booster-Impfung in dieser vulnerablen Patientengruppe erforderlich macht. Zum Schutz der immunsupprimierten Patienten können neben Impfstoffen auch passive Immunisierungen, wie intravenöse Immunglobuline und zusätzliche Maßnahmen wie antivirale Prophylaxe nach Influenza-Exposition notwendig sein.