Associations Between Built Environment Factors and SARS-CoV-2 Infections at the Neighbourhood Level in a Metropolitan Area in Germany.

COVID-19-related health outcomes displayed distinct geographical patterns within countries. The transmission of SARS-CoV-2 requires close spatial proximity of people, which can be influenced by the built environment. Only few studies have analysed SARS-CoV-2 infections related to the built environment within urban areas at a high spatial resolution. This study examined the association between built environment factors and SARS-CoV-2 infections in a metropolitan area in Germany. Polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infections of 7866 citizens of Essen between March 2020 and May 2021 were analysed, aggregated at the neighbourhood level. We performed spatial regression analyses to investigate associations between the cumulative number of SARS-CoV-2 infections per 1000 inhabitants (cum. SARS-CoV-2 infections) up to 31.05.2021 and built environment factors. The cum. SARS-CoV-2 infections in neighbourhoods (median: 11.5, IQR: 8.1-16.9) followed a marked socially determined north-south gradient. The effect estimates of the adjusted spatial regression models showed negative associations with urban greenness, i.e. normalized difference vegetation index (NDVI) (adjusted ß = - 35.36, 95% CI: - 57.68; - 13.04), rooms per person (- 10.40, - 13.79; - 7.01), living space per person (- 0.51, - 0.66; - 0.36), and residential (- 0.07, 0.16; 0.01) and commercial areas (- 0.15, - 0.25; - 0.05). Residential areas with multi-storey buildings (- 0.03, - 0.12; 0.06) and green space (0.03, - 0.05; 0.11) did not show a substantial association. Our results suggest that the built environment matters for the spread of SARS-CoV-2 infections, such as more spacious apartments or higher levels of urban greenness are associated with lower infection rates at the neighbourhood level. The unequal intra-urban distribution of these factors emphasizes prevailing environmental health inequalities regarding the COVID-19 pandemic.

Long-term cellular immune response in immunocompromised unvaccinated COVID-19 patients undergoing monoclonal antibody treatment.

Immunocompromised patients are at increased risk for a severe course of COVID-19. Treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with anti-SARS-CoV-2 monoclonal antibodies (mAbs) has become widely accepted. However, the effects of mAb treatment on the long-term primary cellular response to SARS-CoV-2 are unknown. In the following study, we investigated the long-term cellular immune responses to SARS-CoV-2 Spike S1, Membrane (M) and Nucleocapsid (N) antigens using the ELISpot assay in unvaccinated, mAb-treated immunocompromised high-risk patients. Anti-SARS-CoV-2 mAb untreated though vaccinated COVID-19 immunocompromised patients, vaccinated SARS-CoV-2 immunocompromised patients without COVID-19 and vaccinated healthy control subjects served as control groups. The cellular immune response was determined at a median of 5 months after SARS-CoV-2 infection. Our data suggest that immunocompromised patients develop an endogenous long-term cellular immune response after COVID-19, although at low levels. A better understanding of the cellular immune response will help guide clinical decision making for these vulnerable patient cohorts.

Decline of Humoral Responses 6 Months after Vaccination with BNT162b2 (Pfizer-BioNTech) in Patients on Hemodialysis.

This study analyzed binding and neutralizing antibody titers up to 6 months after standard vaccination with BNT162b2 (two doses of 30 µg each) in SARS-CoV-2 naïve patients (n = 59) on hemodialysis. Humoral vaccine responses were measured before and 6, 12, and 24 weeks after the first vaccination. A chemiluminescent immunoassay (CLIA) was used to quantify SARS-CoV-2 IgG against the spike glycoprotein. SARS-CoV-2 neutralizing activity was tested against the wild-type virus. A multivariable binary regression model was used to identify risk factors for the absence of humoral immune responses at 6 months. At week 6, vaccine-specific seroconversion was detected in 96.6% of all patients with median anti-SARS-CoV-2 IgGs of 918 BAU/mL. At weeks 12 and 24, seroconversion rates decreased to 91.5% and 79.7%, and corresponding median binding antibody titers declined to 298 BAU/mL and 89 BAU/mL, respectively. Neutralizing antibodies showed a decay from 79.6% at week 6 to 32.8% at week 24. The risk factor with the strongest association for vanishing immune responses was low serum albumin (p = 0.018). Regarding vaccine-specific humoral responses 6 months after the standard BNT162b2 vaccination schedule, SARS-CoV-2 naïve patients receiving hemodialysis must be considered at risk of becoming infected with SARS-CoV-2 and being infectious.

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.

SARS-CoV-2 rapid antigen test: Fast-safe or dangerous? An analysis in the emergency department of an university hospital.

The use of Antigen point of care tests (AgPOCT) might be an essential tool to fight the coronavirus disease 2019 (COVID-19) pandemic. Manufacturer information indicates a specificity of about 95% and there is a growing interest to use these tests area-wide. Therefore, it is necessary to clarify whether AgPOCT can be used safely for "rule-in" (detection of positive patients) and for "rule-out" (valid negative testing). Two thousand three hundred and seventy-five patients received polymerase chain reaction (PCR) testing and AgPOCT for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) regardless of symptoms. The positive predictive value of symptomatic and asymptomatic patients was compared with a cut-off threshold cycle (C t ) value of ≤30 and in total. Five hundrded and fifty-one patients tested positive for the SARS-CoV-2 virus by PCR, of whom 35.2% presented without symptoms. In all patients, regardless of their symptoms or C t values, a sensitivity of 68.9% and a specificity of 99.6% were calculated for AgPOCT. In patients with C t values ≤30, a sensitivity of 80.5% (95% confidence interval: ±1.62) and a specificity of 99.6% were shown for all tests (symptomatic/asymptomatic). Highly infectious patients (C t ≤ 20), regardless of symptoms, were reliably detected by the AgPOCT. In infectious patients with C t values ≤30, the test has a sensitivity of about 80% regardless of COVID-19 typical symptoms, which is apparently less than the 96.52% specificity indicated by the manufacturer. Relevant improvement in test sensitivity by querying the patients who are symptomatic and asymptomatic is also not feasible. We strongly suggest that we critically question the use of AgPOCT for "rule-out," as they only provide a supposed safety.

SARS-CoV-2 Seroprevalence in Healthcare Workers in Germany: A Follow-Up Study.

SARS-CoV-2 is a worldwide challenge for the medical sector. Healthcare workers (HCW) are a cohort vulnerable to SARS-CoV-2 infection due to frequent and close contact with COVID-19 patients. However, they are also well trained and equipped with protective gear. The SARS-CoV-2 IgG antibody status was assessed at three different time points in 450 HCW of the University Hospital Essen in Germany. HCW were stratified according to contact frequencies with COVID-19 patients in (I) a high-risk group with daily contacts with known COVID-19 patients (n = 338), (II) an intermediate-risk group with daily contacts with non-COVID-19 patients (n = 78), and (III) a low-risk group without patient contacts (n = 34). The overall seroprevalence increased from 2.2% in March-May to 4.0% in June-July to 5.1% in October-December. The SARS-CoV-2 IgG detection rate was not significantly different between the high-risk group (1.8%; 3.8%; 5.5%), the intermediate-risk group (5.1%; 6.3%; 6.1%), and the low-risk group (0%, 0%, 0%). The overall SARS-CoV-2 seroprevalence remained low in HCW in western Germany one year after the outbreak of COVID-19 in Germany, and hygiene standards seemed to be effective in preventing patient-to-staff virus transmission.

Impaired Humoral Response in Renal Transplant Recipients to SARS-CoV-2 Vaccination with BNT162b2 (Pfizer-BioNTech).

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has a major impact on transplant recipients, with mortality rates up to 20%. Therefore, the effect of established messenger RNA (mRNA)-based SARS-CoV-2 vaccines have to be evaluated for solid organ transplant patients (SOT) since they are known to have poor responses after vaccination. We investigated the SARS-CoV-2 immune response via SARS-CoV-2 IgG detection in 23 renal transplant recipients after two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 following the standard protocol. The antibody response was evaluated once with an anti-SARS-CoV-2 IgG CLIA 15.8 +/- 3.0 days after the second dose. As a control, SARS-CoV-2 IgG was determined in 23 healthcare workers (HCW) and compared to the patient cohort. Only 5 of 23 (22%) renal transplant recipients were tested positive for SARS-CoV-2 IgG antibodies after the second dose of vaccine. In contrast, all 23 (100%) HCWs were tested positive for antibodies after the second dose. Thus, the humoral response of renal transplant recipients after two doses of the mRNA-based vaccine BNT162b2 (Pfizer-BioNTech, Kronach, Germany) is impaired and significantly lower compared to healthy controls (22% vs. 100%; p = 0.0001). Individual vaccination strategies might be beneficial in these vulnerable patients.

Humoral Response to SARS-CoV-2-Vaccination with BNT162b2 (Pfizer-BioNTech) in Patients on Hemodialysis.

mRNA-based SARS-CoV-2 vaccines offer a preventive strategy against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections that is of interest in the care of patients on hemodialysis (HDP). We measured humoral immune responses in 72 HDP after standard vaccination with two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 (Pfizer-BioNTech). Antibody responses were evaluated with an anti-SARS-CoV-2 IgG ChemiLuminescent ImmunoAssay (CLIA) two weeks after the second dose. In addition, SARS-CoV-2 IgG was determined in a control of 16 healthy healthcare workers (HCW). The control group of HCW has shown a strong antibody response with a median (MD (Q1; Q3)) antibody titer of 800.0 AU/mL (520.5; 800.0). In comparison to HCW, HDP under 60 years of age responded equally (597.0 AU/mL (410.5; 800.0), p = 0.051). However, the antibody responses of the HDP negatively correlated with age (r2 = 0.2954 p < 0.0001), leading to significantly lower antibody titers in HDP over 60 years (280.0 AU/mL (45.7; 477.0), p < 0.0001). To thoroughly understand the immunogenicity of the new mRNA-based vaccines in HDP, longitudinal data on the effectiveness and durability of antibody responses are needed. Modifications of immunization schedules should be considered in HDP with low or without antibody responsiveness after standard vaccination to boost immune reactivity and prolong protective effects in these vulnerable patients.

Differential expansion of circulating human MDSC subsets in patients with cancer, infection and inflammation.

BACKGROUND: Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers is hindered by technical pitfalls and a lack of standardized methodology. To overcome this issue, we formed a network through the COST Action Mye-EUNITER (www.mye-euniter.eu) with the goal to standardize and facilitate the comparative analysis of human circulating MDSC in cancer, inflammation and infection. In this manuscript, we present the results of the multicenter study Mye-EUNITER MDSC Monitoring Initiative, that involved 13 laboratories and compared circulating MDSC subsets across multiple diseases, using a common protocol for the isolation, identification and characterization of these cells. METHODS: We developed, tested, executed and optimized a standard operating procedure for the isolation and immunophenotyping of MDSC using blood from healthy donors. We applied this procedure to the blood of almost 400 patients and controls with different solid tumors and non-malignant diseases. The latter included viral infections such as HIV and hepatitis B virus, but also psoriasis and cardiovascular disorders. RESULTS: We observed that the frequency of MDSC in healthy donors varied substantially between centers and was influenced by technical aspects such as the anticoagulant and separation method used. Expansion of polymorphonuclear (PMN)-MDSC exceeded the expansion of monocytic MDSC (M-MDSC) in five out of six solid tumors. PMN-MDSC expansion was more pronounced in cancer compared with infection and inflammation. Programmed death-ligand 1 was primarily expressed in M-MDSC and e-MDSC and was not upregulated as a consequence of disease. LOX-1 expression was confined to PMN-MDSC. CONCLUSIONS: This study provides improved technical protocols and workflows for the multi-center analysis of circulating human MDSC subsets. Application of these workflows revealed a predominant expansion of PMN-MDSC in solid tumors that exceeds expansion in chronic infection and inflammation.

The detection of BKPyV genotypes II and IV after renal transplantation as a simple tool for risk assessment for PyVAN and transplant outcome already at early stages of BKPyV reactivation.

BACKGROUND: After reactivation the BK-polyomavirus (BKPyV) associated nephropathy (PyVAN) is observed in 1-10% of renal transplant recipients, of which up to 80% undergo graft failure. BKPyV reactivation after renal transplantation was associated with donor-derived serotypes against which the recipient has no immunological protection. However, PyVAN risk assessment seroactivity testing is a time-consuming and cost intensive process. OBJECTIVES: Since BKPyV serotypes can be attributed to distinct genotypes I to IV, in the present study we retrospectively analyzed whether a simple PCR-based BKPyV genotyping assay might be a fast and inexpensive method to assess the risk for PyVAN and transplant outcome already at early stages of BKPyV reactivation. STUDY DESIGN: 56 patients who were renal transplanted and tested positive for BKPyV viremia were included into the study. The BKPyV-VP1-coding sequences were PCR-amplified, sequenced, and subjected to genotyping. For group specific analysis patients were grouped in genotype I (n = 46) and a second group including genotype II and IV (n = 10) and associated with their clinical outcomes. RESULTS: The most abundant genotype I was detected in 46 of 56 (82%) patients, however, in the genotype II and IV group PyVAN was twice as frequent as compared to the genotype I group 24 months after transplantation (8 of 10 (80%) vs. 17 of 46 (37%); p = 0.001). Accordingly, graft failure was significantly more frequent in the genotype II and IV group (3 of 10 (30%) vs. 2 of 46 (4%); p = 0.007). CONCLUSION: PCR-based BKPyV genotyping might represent a fast and inexpensive method to assess the risk for PyVAN and transplant outcome already at early stages of BKPyV reactivation even if matched samples of the donor are not available.

Impact of low-level BK polyomavirus viremia on intermediate-term renal allograft function.

BACKGROUND: BK polyomavirus (BKPyV)-associated nephropathy (PyVAN) is a significant cause of premature renal transplant failure. High-level BKPyV viremia is predictive for PyVAN; however, low-level BKPyV viremia does not necessarily exclude the presence of PyVAN. As data are limited regarding whether or not low-level BKPyV viremia has an effect on intermediate-term graft outcome, this study analyzes the impact of low-level BKPyV viremia on intermediate-term graft function and outcome compared with high-level viremia and non-viremic patients. METHODS: All renal transplant patients received follow-up examinations at the Department of Nephrology, University Hospital Essen. Patients were screened for BKPyV viremia and stratified into three groups according to their maximum BKPyV load in serum (low-level viremia, high-level viremia, and no viremia). RESULTS: In 142 of 213 (67%) patients, BKPyV was never detected in serum; 42 of 213 (20%) patients were found positive for low-level viremia (≤104 copies/mL); and 29 of 213 (13%) patients showed high-level viremia (>104 copies/mL). No significant differences regarding transplant function and graft failure were observed between patients without BKPyV viremia (delta estimated glomerular filtration rate [eGFR] +0.1 mL/min [month 1 vs last visit at month 44]) and patients with low-level BKPyV viremia (delta eGFR -1.7 mL/min). In patients with high-level viremia, transplant function was significantly restricted (delta eGFR -6.5 mL/min) compared with low-level viremia until the last visit at 44 ± 9.7 months after transplantation. Although the graft function and graft loss were worse in the high-level viremia group compared with no viremia (eGFR 37 vs 45 mL/min), the difference was not significant. CONCLUSIONS: High-level viremia was associated with impaired graft function. In contrast, low-level BKPyV viremia had no significant impact on intermediate-term graft function.

Increased resistance of gram-negative urinary pathogens after kidney transplantation.

BACKGROUND: Urinary tract infection is the most common complication after kidney transplantation. It can cause severe sepsis and transplant loss. Emergence of drug resistance among gram-negative urinary pathogens is the current challenge for urinary tract infection treatment after kidney transplantation. METHODS: This study analyzes the antimicrobial susceptibility of gram-negative urinary pathogens after kidney transplantation from 2009 to 2012 at the Transplant Outpatient Clinic of the University Hospital Essen, Germany. Kidney transplant patients at the University Hospital Essen receive regular follow up examinations after transplantation. Midstream urines were examined for bacteriuria at each follow up visit. RESULTS: From 2009 to 2012 15.741 urine samples were obtained from 859 patients. In 2985 (19%) samples bacterial growth was detected. The most frequently detected gram-negative bacteria were E.coli 1109 (37%), Klebsiella spp. 242 (8%) and Pseudomonas aeruginosa 136 (4.5%). Klebsiella spp. showed a significant increase of resistance to trimethoprim-sulfamethoxazole by 19% (p = 0.02), ciprofloxacin by 15% (p = 0.01) and ceftazidime by 17% (p = 0.004). E.coli and P. aeruginosa isolates presented no significant differences of antimicrobial susceptibility to the analyzed antibiotics. CONCLUSIONS: Antimicrobial resistance of Klebsiella spp. increased significant to trimethoprim-sulfamethoxazole, ciprofloxacin and ceftazidime from 2009 to 2012.