Christoph Daniel Spinner

BACKGROUND: Vaccinations against COVID-19 were integrated into routine care in Germany in April 2023. However, evidence of the impact of seasonal vaccination remains limited. AIM: To assess the clinical and economic impact of COVID-19 vaccination in routine care during the early SARS-CoV-2-endemic phase in Germany. METHODS: A retrospective cohort study using statutory health insurance data from two German federal states (Saxony and Thuringia), covering over 3 million individuals, was conducted. Adults aged ≥ 18 years vaccinated against COVID-19 between 1 September and 30 November 2023 were matched 1:1 with unvaccinated individuals using propensity scores. Outcomes during the 4-month follow-up included occurrence of SARS-CoV-2 infection, long COVID, other respiratory infections, hospitalisations, mortality, healthcare costs and indirect costs caused by sick leave. Rate and hazard ratios (RR, HR) with 95% confidence intervals (CI) were calculated. Sensitivity analyses tested robustness. RESULTS: A total of 146,132 individuals (73,066 per group) were matched. COVID-19 vaccination was associated with reduced rates of long COVID (RR: 0.43; 95% CI: 0.26–0.70), respiratory infections (RR: 0.91; 95% CI: 0.87–0.95) and COVID-19-related hospitalisations (RR: 0.41; 95% CI: 0.31–0.54). All-cause mortality was 25% lower among COVID-19-vaccinated individuals (HR: 0.76; 95% CI: 0.70–0.82). Healthcare costs were lower in the vaccinated cohort, particularly for inpatient care, e.g. EUR 1 million savings in COVID-19-related hospitalisations. Indirect costs caused by sick leave were also reduced by EUR 1.3 million. CONCLUSION: Seasonal COVID-19 vaccinations in routine care settings were associated with substantial clinical and economic benefits. These real-world findings support continued implementation of national immunisation recommendations during the endemic phase of SARS-CoV-2 circulation.

Background: While pre-exposure prophylaxis (PrEP) can prevent HIV acquisition, associated behavioral changes may increase risk of acquiring other sexually transmitted infections (STIs). Methods: The prospective multicenter BRAHMS study enrolled men who were HIV negative, had sex with men, and were aged 18 to 55 years and reported an increased risk to acquire STI. At 3-month intervals for up to 12 months, participants answered questionnaires and underwent site-specific screening for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG), and syphilis. We computed 3-month incidence rates and rate ratios, and we employed multilevel mixed effects logistic regression to determine odds ratios (ORs) and 95% CIs for factors associated with any incident STI. Results: The mean age of 1017 participants was 33 years, 54.7% used PrEP at enrollment, and 83.7% reported PrEP use overall. Any STI was diagnosed in 71.8% (CT, 40.4%; MG, 38.5%; NG, 36.0%; syphilis, 10.1%; HIV, 0.5%). PrEP users exhibited a higher prevalence for anorectal infections with CT (35.3% vs 20.5%, P < .05), MG (31.4% vs 23.5%, P < .05), and NG (26.1% vs 16.9%, P < .05). CT incidence decreased from 46.8 cases per 100 person-years to 35.7 (−23.7%, P < .05), and NG incidence decreased from 41.6 cases per 100 person-years to 30.7 (−26.2%, P < .05). MG and syphilis incidence remained stable. Factors independently associated with STI incidence were as follows: symptoms (OR, 1.85; 95% CI, 1.46–2.34), condomless anal sex with >5 casual partners (OR, 1.79; 95% CI, 1.49–2.14), recreational drug use (OR, 1.76; 95% CI, 1.46–2.12), being born abroad (OR, 1.49; 95% CI, 1.19–1.87), PrEP use (OR, 1.29; 95% CI, 1.05–1.58), and having a moderately or largely increased self-perceived risk of HIV (OR, 1.26 [95% CI, 1.03–1.53]; OR, 1.33 [95% CI, 1.02–1.74], respectively). Conclusions: PrEP use was associated with increased STI risk in our cohort. CT and NG incidence decreased in a structured test-and-treat setting.

Background: Data on the impact of completing 2 doses of the modified vaccinia Ankara vaccine and/or smallpox vaccination in childhood on Mpox disease severity remain limited. During the last months of 2024, Germany faced a second Mpox wave, providing the opportunity to study the impact of different vaccine regimens including smallpox vaccination. Methods: Retrospective analysis of all cases diagnosed at 17 participating German centers 2022–2024. Cases were grouped according to smallpox vaccine history: “unvaccinated,” “incomplete” (vaccinations only during childhood and/or only one MVA BN), “complete” (2 MVA BN > 1 month prior to Mpox diagnosis). Disease severity was assessed by a 7-item Mpox Severity Scoring System (MPOX-SSS). Results: Of 273 Mpox infections, 42% occurred in men who have sex with men (MSM) living with HIV (median CD4 724 cells/µl, 91% <50 HIV-RNA copies/ml), 58% occurred in MSM without HIV, most of them using HIV PrEP. Median age was 38 years (IQR 30–44). Vaccinated individuals demonstrated lower MPOX-SSS scores compared to unvaccinated individuals (mean score 5.46 vs 7.15, P < .001). Vaccinated individuals also had less fever (23% vs 59%, P < .001), headaches/chills (29% vs 54%, P < .001), and swollen lymph nodes (38% vs 56%, P = .02). Conclusions: Both incomplete and complete vaccine courses including smallpox vaccination during childhood appear to reduce Mpox disease severity and symptoms. In settings of limited vaccine resources, unvaccinated risk groups should be prioritized.

The COVID-19 pandemic has starkly exposed queryPlease check author names and affiliation if presented correctly.vulnerabilities in the management of surveillance and testing. Significant challenges associated with physical tests, i.e., PCR and antigen tests, include their high cost, resource-intensive nature, turnaround time, and sensitivity. Although the literature has underscored the potential of Machine Learning-based methods for the digital diagnosis of COVID-19, developing high-performing models crucially depends on extensive datasets exceeding the amount available in one healthcare institution. Federated Machine Learning offers a solution to that dilemma. The aim of this research is to evaluate the potential impact of Federated Learning-based digital COVID-19 diagnosis on the trajectory of a pandemic. Therefore, we design a multidimensional evaluation framework, consisting of a simulation study utilizing real-world lab parameters from multiple hospitals and a newly developed performance indicator, named Testing Evaluation for Pandemics. We find that Federated Learning can significantly support the decision-making process of diagnosing COVID-19 at the beginning of a pandemic while saving scarce resources. However, a warm-up phase is needed until constant performance similar to physical tests is reached. In addition, lab parameters have a high prediction power for the diagnosis and are well suited because of patient welfare reasons.

The ROUTINE-COV19 study explores the burden of COVID-19 in Germany during the early endemic phase, assessing disease patterns and their impact on the healthcare system from 1 July 2022 to 30 June 2023. Using anonymized statutory health insurance data from over 3 million individuals in Thuringia and Saxony, COVID-19 cases were identified through diagnostic codes, with severe and critical cases defined by hospitalization and intensive care criteria. The study focused on high-risk populations as identified by the German Immunization Technical Advisory Group. During the study period, 414,648 new COVID-19 cases were documented, with peaks in October 2022 and March 2023. Severe cases occurred at a rate of 241.6 per 100,000 persons, with in-hospital mortality exceeding 12%. Critical cases requiring intensive care had an in-hospital mortality rate of 32.2%. COVID-19-related hospitalizations averaged 9.94 days, generating direct costs of EUR 64.9 million, while indirect costs from work absenteeism amounted to EUR 454.3 million, representing 7.5% of all-cause absenteeism costs. Despite entering an endemic phase, COVID-19 continues to pose a substantial burden, particularly among older adults and those with pre-existing cardiovascular conditions.

People living with HIV treated during acute infection are the group for whom achieving functional cure appears most viable. Follicular CD8 ⁺ T cells could contribute to HIV reservoir clearance by accessing B cell follicles through CXCR5 expression. This study examines peripheral follicular CD8 ⁺ T cells using flow cytometry, transcriptome analyses, and functional assays in people treated during acute ( n = 37) and chronic ( n = 18) infection, as well as in individuals naturally controlling HIV ( n = 20) and living without HIV ( n = 10). Our results reveal that early, as opposed to late, treatment initiation preserves antiviral effector functions of follicular CD8 ⁺ T cells, which are further enhanced by PD1 inhibition. We also identify a correlation between follicular CD8 ⁺ T cells and intact proviral HIV DNA levels in acute, but not chronic, infection. Longitudinal transcriptomic analysis of peripheral effector cells after 48 weeks of suppressive therapy indicated traits of recent antigen exposure, suggesting potential recirculation into lymphoid tissue. These findings underscore the pivotal role of follicular CD8 ⁺ T cells in anti-HIV responses and support investigating targeted cure strategies, such as anti-PD1 therapy, especially in individuals initiating treatment during acute infection.

Background: Persistent COVID-19 (pCOVID-19) in immunocompromised patients is characterized by unspecific symptoms and pulmonary infiltrates due to ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replication. Treatment options remain unclear, leading to different approaches, including combination therapy and extended durations. The purpose of this study was to assess the efficacy and safety of antiviral therapies for pCOVID-19 in immunocompromised patients since the Omicron surge. Methods: We searched MEDLINE and Scopus from 1 January 2022 to 6 August 2024 for cohort studies and case series on nirmatrelvir/ritonavir, remdesivir, ensitrelvir and molnupiravir. Evidence certainty was rated using Grading of Recommendations Assessment, Development, and Evaluation for outcomes including viral clearance, recurrence/relapse, mortality, adverse events (AEs) and symptom resolution. Results: Thirteen studies involving 127 cases were included. Evidence certainty was very low. In combination therapy with at least two direct antiviral agents, viral clearance was 79%, with a 16% recurrence rate. All-cause mortality was 9%, and mortality was 6% while SARS-CoV-2 positive. In 47 cases, AEs were reported in 11%. Symptom resolution ranged from 3 to 6 days in two studies. In combination therapy with one direct antiviral agent and passive immunization, viral clearance was 89%, with an 11% recurrence rate and no deaths. In four documented cases, no AEs were observed. In monotherapy, viral clearance was 100%, with a 15% recurrence rate. One death, unrelated to SARS-CoV-2, occurred. In 12 documented cases, no AEs were observed. Conclusions: Based on very low certainty evidence, combining one direct antiviral with passive immunization resulted in high rates of viral clearance and few recurrences. AEs occurred in cases treated with at least two direct antivirals. Controlled studies are needed.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact. The emergence of several variants during the pandemic has presented numerous challenges in preventing and managing this disease. The development of vaccines has played a pivotal role in controlling the pandemic, with a significant portion of the global population being vaccinated. This, along with the emergence of less virulent SARS-CoV-2 variants, has led to a reduction in the severity of COVID-19 outcomes for the overall population. Nevertheless, individuals with immunocompromising conditions continue to face challenges given their suboptimal response to vaccination and vulnerability to severe COVID-19. This expert review synthesizes recent published evidence regarding the economic and human impact of COVID-19 on such individuals. The literature suggests that rates of hospitalization, intensive care unit admission, and mechanical ventilation use were high during the pre-Omicron era, and remained high during Omicron and later, despite vaccination for this population. Moreover, studies indicated that these individuals experienced a negative impact on their mental health and health-related quality of life (HRQoL) compared to those without immunocompromising conditions, with elevated levels of anxiety, depression, and distress reported. Further, these individuals with immunocompromising conditions experienced substantial costs associated with COVID-19 and loss of income during the pandemic, though the evidence on the economic burden of COVID-19 in such individuals is limited. Generally, COVID-19 has increased healthcare resource use and costs, impaired mental health, and reduced HRQoL in those with varied immunocompromising conditions compared to both those without COVID-19 and the general population—underscoring the importance of continued real-world studies. Ongoing research is crucial to assess the ongoing burden of COVID-19 in vaccinated individuals with immunocompromising conditions who are still at risk of severe COVID-19 outcomes to ensure their needs are not disproportionately worse than the general population.

Background: The universal availability of smartphones has created new opportunities for innovative telemedicine applications in health care. The COVID-19 pandemic has heightened the demand for contactless health care services, making SARS-CoV-2 polymerase chain reaction (PCR) testing a crucial component of pandemic containment. Objective: This feasibility study aimed to examine a comprehensive telemedicine approach for SARS-CoV-2 testing, focusing on the practicality, user satisfaction, and economic implications of self-sampling guided by a telemedicine platform. Methods: The study process involved shipping self-sampling kits, providing instructions for at-home sample collection, processing biomaterials (swabs and capillary blood), communicating test results, and providing interoperable data for clinical routine and research through a medical mobile app. A total of 100 individuals were randomly assigned to either the conventional health care professional (HCP)–performed SARS-CoV-2 testing group (conventional testing group, CG) or the telemedicine-guided SARS-CoV-2 self-sampling approach (telemedicine group, TG). Feasibility of the TG approach, user satisfaction, user-centered outcomes, and economic aspects were assessed and compared between the groups. Results: In the TG group, 47 out of 49 (95%) individuals received a self-sampling kit via mail (76%) individuals successfully returned at least one sample for diagnostics. SARS-CoV-2 PCR tests were conducted in 95% () of TG cases compared with 88% () in the CG. Users in the TG reported high satisfaction levels with ease of use (5.2/7), interface satisfaction (5.2/7), and usefulness (4.3/7). A microcosting model indicated a slightly higher cost for the TG approach than the CG approach. The TG demonstrated the potential to facilitate interoperable data transmission by providing anonymized, standardized datasets for extraction using Health Level 7-Fast Healthcare Interoperability Resources. This supports the national COVID-19 Data Exchange Platform and facilitates epidemiological evaluation based on the German COVID Consensus dataset. Conclusion: These preliminary findings suggest that a telemedicine-based approach to SARS-CoV-2 testing is feasible and could be integrated into existing hospital data infrastructures. This model has the potential for broader application in medical care, offering a scalable solution that could improve user satisfaction and treatment quality in the future.

Patients with hematologic malignancies still face a significant risk of severe coronavirus disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-neutralizing monoclonal antibody combination tixagevimab/cilgavimab (TIX/CGB) could be administered to immunocompromised patients for pre-exposure prophylaxis (PrEP) before the emergence of TIX/CGB-resistant COVID-19 Omicron variants. TIX/CGB application could be carried out regardless of the host’s immune response to previous active SARS-CoV-2 vaccinations or infections. Because the efficacy of COVID-19 PrEP remains unclear, especially in SARS-CoV-2-seropositive patients, German national guidelines recommended TIX/CGB PrEP only for SARS-CoV-2-seronegative patients in addition to an intensified active vaccination schedule. Having followed these guidelines, we now report the characteristics and outcomes of 54 recipients of TIX/CGB PrEP in SARS-CoV-2-seronegative patients with hematological disease from a German tertiary medical center and compare them to 125 seropositive patients who did not receive any PrEP. While the number of patients with B-cell lymphomas was significantly higher in the seronegative cohort (33 (61%) vs. 18 (14%) cases, p < 0.01), patients with myeloid diseases were significantly more frequent in the seropositive cohort (51 (41%) vs. 5 (9%) cases, p < 0.01). Strikingly, patients who had undergone allogeneic hematopoietic stem cell transplantation were significantly more likely (forty-nine (39%) vs. six (11%) cases, p < 0.01) to be SARS-CoV-2 seropositive. We observed that prophylactic application of TIX/CGB PrEP to a highly vulnerable group of SARS-CoV-2-seronegative patients resulted in a similar number of COVID-19 breakthrough infections compared to the untreated seropositive control group (16 (32%) vs. 39 (36%), p = 0.62) and comparable COVID-19-related outcomes like hospitalization and oxygen requirement throughout an extended follow-up period of 12 months. In conclusion, our results support the tailored approach of administering TIX/CGB PrEP only to SARS-CoV-2-seronegative patients during the COVID-19 pandemic and might provide a rationale for similar strategies during future outbreaks/diseases, especially in times of initial limited availability and/or financial constraints.