Impact of age and comorbidities on SARS-CoV-2 vaccine-induced T cell immunity.

BACKGROUND: Older age and chronic disease are important risk factors for developing severe COVID-19. At population level, vaccine-induced immunity substantially reduces the risk of severe COVID-19 disease and hospitalization. However, the relative impact of humoral and cellular immunity on protection from breakthrough infection and severe disease is not fully understood. METHODS: In a study cohort of 655 primarily older study participants (median of 63 years (IQR: 51-72)), we determined serum levels of Spike IgG antibodies using a Multiantigen Serological Assay and quantified the frequency of SARS-CoV-2 Spike-specific CD4 + and CD8 + T cells using activation induced marker assay. This enabled characterization of suboptimal vaccine-induced cellular immunity. The risk factors of being a cellular hypo responder were assessed using logistic regression. Further follow-up of study participants allowed for an evaluation of the impact of T cell immunity on breakthrough infections. RESULTS: We show reduced serological immunity and frequency of CD4 + Spike-specific T cells in the oldest age group (≥75 years) and higher Charlson Comorbidity Index (CCI) categories. Male sex, age group ≥75 years, and CCI > 0 is associated with an increased likelihood of being a cellular hypo-responder while vaccine type is a significant risk factor. Assessing breakthrough infections, no protective effect of T cell immunity is identified. CONCLUSIONS: SARS-CoV-2 Spike-specific immune responses in both the cellular and serological compartment of the adaptive immune system increase with each vaccine dose and are progressively lower with older age and higher prevalence of comorbidities. The findings contribute to the understanding of the vaccine response in individuals with increased risk of severe COVID-19 disease and hospitalization.

Vaccination has proven very effective in protecting against severe disease and hospitalization of people with COVID-19, the disease caused by SARS-CoV-2. It is still unclear, however, how the different components of the immune system respond to SARS-CoV-2 vaccination and protect from infection and severe disease. Two of the most predominant components of the immune system are specialized proteins and cells. The proteins circulate in the blood and help clear the virus by binding to it, while the cells either kill the virus or help other cells to produce more antibodies. Here, we examined the response of these two components to the SARS-CoV-2 vaccine in 655 Danish citizens. The response of both components was lower in people over 75 years old and with other diseases. These findings help in understanding the immune responses following SARS-CoV-2 vaccination in people at increased risk of severe symptoms of COVID-19.

Cohort Profile:The Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 vaccines (ENFORCE).

PURPOSE: The ENFORCE cohort is a national Danish prospective cohort of adults who received a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as part of the Danish National SARS-CoV-2 vaccination programme. It was designed to investigate the long-term effectiveness, safety and durability of SARS-CoV-2 vaccines used in Denmark. PARTICIPANTS: A total of 6943 adults scheduled to receive a SARS-CoV-2 vaccine in the Danish COVID-19 vaccination programme were enrolled in the study prior to their first vaccination. Participants will be followed for a total of 2 years with five predetermined follow-up visits and additional visits in relation to any booster vaccination. Serology measurements are performed after each study visit. T-cell immunity is evaluated at each study visit for a subgroup of 699 participants. Safety information is collected from participants at visits following each vaccination. Data on hospital admissions, diagnoses, deaths and SARS-CoV-2 PCR results are collected from national registries throughout the study period. The median age of participants was 64 years (IQR 53-75), 56.6% were women and 23% were individuals with an increased risk of a serious course of COVID-19. A total of 340 (4.9%) participants tested positive for SARS-CoV-2 spike IgG at baseline. FINDINGS TO DATE: Results have been published on risk factors for humoral hyporesponsiveness and non-durable response to SARS-CoV-2 vaccination, the risk of breakthrough infections at different levels of SARS-CoV-2 spike IgG by viral variant and on the antibody neutralising capacity against different SARS-CoV-2 variants following primary and booster vaccinations. FUTURE PLANS: The ENFORCE cohort will continuously generate studies investigating immunological response, effectiveness, safety and durability of the SARS-CoV-2 vaccines. TRIAL REGISTRATION NUMBER: NCT04760132.

Determinants of Antibody Response to a Third SARS-CoV-2 mRNA Vaccine Dose in Solid Organ Transplant Recipients: Results from the Prospective Cohort Study COVAC-Tx.

BACKGROUND: We studied factors related to humoral response in solid organ transplant (SOT) recipients following a three-dose regimen of an mRNA-based SARS-CoV-2 vaccine. METHOD: This was a prospective study of SOT recipients who received a third homologous dose of the BNT162b2 (Pfizer-BioNTech) vaccine. The anti-spike S1 IgG response was measured using the SARS-CoV-2 IgG II Quant assay (Abbott Laboratories) with a cut-off of 7.1 BAU/mL. Multiple logistic regression was used to determine the factors associated with humoral response. RESULTS: In total, 395 SOT recipients were included. Anti-spike IgG was detected in 195/395 (49.4%) patients after the second dose and 261/335 (77.9%) patients after the third dose. The overall mean increase in antibody concentration after the third dose was 831.0 BAU/mL (95% confidence interval (CI) 687.4-974.5) and 159 (47.5%) participants had at least a 10-fold increase in antibody concentration after the third dose. The increase in antibody concentration was significantly higher among patients with detectable antibodies after the second dose than those without. Cumulative time from transplantation and liver recipients was positively associated with an antibody response, whereas older age, administration of prednisolone, and proliferation inhibitors were associated with diminished antibody response. CONCLUSION: Although the third dose of the BNT162b2 vaccine improved humoral responses among SOT non-responders following the second dose, the overall response remained low, and 22.1% did not develop any response. Patients at risk of a diminished vaccine response require repeated booster doses and alternative treatment approaches.

The prevalence of diabetes among tuberculosis patients in Denmark.

SETTING: It is estimated that 25% of the world's population are infected with Mycobacterium tuberculosis and that 463 million people are living with diabetes mellitus (DM), a number that is increasing. Patients with DM have three times the risk of developing tuberculosis (TB) and there is significant interaction between DM and TB, suggesting that DM affects not only risk of TB but also TB presentation, treatment response and outcome. OBJECTIVE: The aim was determining the prevalence of DM among TB patients in Denmark and to assess risk factors. DESIGN: Patient files from all notified TB cases in Denmark from 2009 to 2014 were retrospectively assessed. RESULTS: In total, 1912 patients were included and 5.0% had DM. Patients with DM were older, had more comorbidities, came from outside Denmark, and had a higher mortality compared to non-DM-patients. None of the patients from Greenland had DM. Patients with low socio-economic status had a low prevalence of DM. We found a higher prevalence of DM among Danish-born < 54 year and migrant ≥ 75 year compared to a Danish background population. CONCLUSION: We found a higher prevalence of DM among TB patients with known risk factors, and a surprisingly low prevalence among patients with low socioeconomic status and patients from Greenland.

Oral and anal carriage of Neisseria meningitidis among sexually active HIV-infected men who have sex with men in Denmark 2014-15.

INTRODUCTION: Outbreaks of invasive meningococcal disease (IMD) among men who have sex with men (MSM) caused by a hypervirulent, non-encapsulated Neisseria meningitidis (Nm) clone belonging to genogroup C have been described. We aimed to determine the oral and anal carriage rates and genogroups of Nm among MSM living with HIV. METHODS: Sexually active MSM living with HIV were included. A questionnaire, an oral wash sample and an anal swab were collected at baseline and 12 months follow-up. Identification of Nm and genogrouping was performed using real-time polymerase chain reaction analysis. RESULTS: Among 82 MSM, the Nm carriage rate was 31.7% (95% CI 21.9-42.9) at baseline. The oral carriage rate was 24.4% (95% CI 15.6-35.1) and the anal rate was 11.0% (95% CI 5.1-19.8). Non-groupable Nm were most prevalent followed by genogroup B and genogroup Y. Rates were similar at follow-up. CONCLUSION: Strains of Nm were detected in both oral washes and anal samples in our study. Our results suggest that Nm may be transmitted sexually among MSM. Non-groupable Nm were predominant in our population and no genogroup C Nm were detected.

The Epidemiology and Clinical Characteristics of Pediatric Tuberculosis in Denmark 2009-2014 Highlights Targets for Prevention.

BACKGROUND: In Western Europe, most pediatric tuberculosis (TB) cases occur among immigrants; however, data are rarely stratified by first/second-generation immigrants and many cases may be preventable. METHODS: This was a nationwide study of children <18 years with TB from 2009 to 2014 in Denmark. Demographic, clinical, microbiologic and treatment outcome data were obtained from registers and medical records. RESULTS: We identified 145 cases; 99 were immigrants (68%) of which 54 (55%) were second-generation immigrants. Most first-generation immigrants (73%) were diagnosed by passive case finding as was half the second-generation immigrants (52%), in contrast to Danish children who were mostly diagnosed by active case finding (70%). Symptoms were often nonspecific, and one-third of the children had normal blood tests at time of diagnosis. First-generation immigrants were most often infected abroad (84%) as opposed to Danish children (9%) and second-generation immigrants (30%). Approximately one-third of the children represented cases of TB disease that could possibly have been prevented by screening or rigorous contact tracing. The overall treatment success rate was 97%, and cases of unsuccessful treatment were restricted to immigrant adolescents. CONCLUSIONS: The majority of pediatric TB in Denmark occurred among immigrant children with symptomatic TB, whereas more Danish children were diagnosed at earlier disease stages. Almost one-third of TB cases may represent missed opportunities to prevent TB disease. Improvements include enhanced adult case detection with comprehensive contact investigation among children, tailored screening and vaccination of immigrant children, and raised awareness of diagnosing and treating latent TB infection in children.

Possible adverse effects of the quadrivalent human papillomavirus vaccine in the Region of Southern Denmark: a retrospective, descriptive cohort study.

INTRODUCTION: Since the introduction of the quadrivalent human papillomavirus vaccine, young girls and women have reported a broad range of symptoms. These have been described as possible adverse effects of the vaccine. In this study, we describe demographic characteristics, symptomatology, clinical and laboratory test results in patients referred with suspected adverse effects in the Region of Southern Denmark. METHODS: We conducted a retrospective, descriptive study. The patients filled out a questionnaire, were interviewed by a doctor and received a standard physical examination and laboratory tests. RESULTS: The study comprised 200 patients. The median age at referral was 22 (interquartile range (IQR): 19.5-26) years, and age at first vaccination was 14 (IQR: 12-21) years. The most common symptoms were headache (93%), fatigue/tiredness (93%) and dizziness when standing up (90%). The median number of symptoms in each patient was 15. Five patients (2.5%) were diagnosed with postural orthostatic tachycardia syndrome (POTS). Of all patients, 183 (91.5%) were terminated without a somatic diagnosis, one patient (0.5%) was terminated with a functional disorder and 11 patients (5.5%) were still in diagnostic workup when the present study concluded. CONCLUSIONS: The patients reported a wide range of symptoms. We found an overall low prevalence of POTS. It should be further investigated whether these patients might suffer from a functional disorder rather than from adverse effects associated with the vaccine. FUNDING: none. TRIAL REGISTRATION: not relevant.