BACKGROUND:Patients admitted with viral respiratory tract infections are at risk of bacterial co-infections, often requiring antibiotics. Standard bacterial cultures may take days to yield results, making early indicators of bacterial co-infection a potential asset. METHODS:In a retrospective regionwide cohort study, we included all patients admitted to a hospital in the Central Denmark Region with COVID-19, influenza, or respiratory syncytial virus (RSV) in the period February 2019 to February 2024. Further inclusion criteria were having a blood sample taken for procalcitonin measurement and blood cultures within 72 h of admission. We evaluated the diagnostic value of procalcitonin compared to other inflammatory markers. RESULTS:There were 1,670 patients fulfilling the inclusion criteria. The majority 1,556 (92.2%) were infected with SARS-CoV-2, 51 (3.7%) with influenza A, 1 (0.1%) with influenza B, 45 (2.7%) with RSV, and 17 (1.0%) with multiple viruses. Blood cultures were positive in 43 (2.6%) of the patients after a median of 67.4 h from time of admission. Median procalcitonin levels were higher in patients with bacteraemia (1.7 µg/L) than in patients without bacteraemia (0.2 µg/L. Overall, procalcitonin cut-off at >0.25 µg/L and >0.50 µg/L tended to have higher sensitivity, specificity, positive and negative predictive values than C-reactive protein (CRP) > 100 mg/L and total leukocyte count >10 × 109 cells/L, although the numerical differences were small. Overall diagnostic performance for bacterial pneumonia was lower. CONCLUSIONS:All biomarkers had relatively low sensitivity for bacteraemia and bacterial pneumonia in patients with viral respiratory tract infection.

BACKGROUND:Coadministering vaccines can effectively enhance vaccination uptake in adults. Despite the potential benefits, there is limited data supporting this practice. We investigated the immunogenicity and safety of coadministering coronavirus disease 2019 (COVID-19) messenger RNA, influenza, and pneumococcal (PPSV23) vaccines in adults. METHODS:As part of the national vaccination program, 3104 adults received a fourth dose (second booster) of an messenger RNA COVID-19 vaccine alone or coadministered with an influenza vaccine, with or without PPSV23 from January to December 2022. We measured severe acute respiratory syndrome coronavirus 2 anti-spike and anti-receptor binding domain (RBD) immunoglobulin G (IgG) concentrations and neutralization activity before and 1 month after vaccination. We estimated the odds of a ≥2-fold geometric mean fold rise (GMFR) and adverse events (AEs) using logistic regression models. RESULTS:The median age of the 3104 participants was 70 years (interquartile range: 60-77); 1670 (54%) were female. Anti-spike IgG GMFRs were 1.95, 1.56, and 1.42, whereas for neutralization activity, values were 8.99, 12.42, and 8.23, in the COVID-19, COVID-19 + influenza, and COVID-19 + influenza + PPSV23 groups, respectively. The adjusted odds of a ≥2-fold anti-spike IgG GMFR were 0.64 (P < .001) and 0.43 (P < .001), and for neutralization activity, 0.96 (P = .833) and 0.97 (P = .954), for COVID-19 + influenza and COVID-19 + influenza + PPSV23, respectively. The odds for anti-RBD GMFRs followed similar patterns. Systemic AEs were more common in the COVID-19 + influenza + PPSV23 group (adjusted odds ratio: 2.04, P < .001), though no serious AEs were reported. CONCLUSIONS:Coadministering COVID-19, influenza, and PPSV23 vaccines seems feasible, without significantly impairing neutralizing antibody responses. These findings support the recommendation for vaccine coadministration in adults.

Objective Persistent symptoms after SARS CoV-2 infection, often designated as "long COVID”, continue to be an ongoing health issue. Previously, we reported electromyography (EMG) and single fiber EMG (SFEMG) abnormalities in long COVID. This study aimed to assess the long-term neuromuscular manifestations of long COVID. Methods In this follow-up study, fifty patients (39 females and 11 males, mean age at baseline: 48.1 ± 9.3 years) with long COVID showing myopathic (EMG and/or abnormal SFEMG at diagnosis were re-evaluated. The disease duration was 1.2 ± 0.6 years at baseline. The mean follow-up interval was 1.38 years. Quantitative EMG (qEMG) was performed on the biceps brachii (BB), vastus medialis (VM), and tibialis anterior (TA), while SFEMG was performed on the extensor digitorum communis (EDC) and TA, at baseline and follow-up on the same muscles and side. EMG, SFEMG, and clinical scores were compared using paired parametric or nonparametric tests. Results Fatigue Assessment Scale (FAS) scores were unchanged (35.8 ± 7.7 vs 34.0 ± 9.4; p > 0.05). Motor unit potential (MUP) amplitudes and durations increased in BB, TA, and VM (p = 0.0001), while the frequency of polyphasic potentials remained unchanged (p > 0.05). SFEMG findings in TA and EDC were also unchanged (p > 0.05). At baseline, 78% of individuals showed myopathic qEMG and 54% abnormal SFEMG; at follow-up, 18% had myopathic qEMG, 56% abnormal SFEMG, and 40% showed normal EMG and SFEMG. Discussion Myopathic changes decreased over time; however, SFEMG abnormalities and clinical scores remained persistent. These findings suggest ongoing neuromuscular dysfunction, although other mechanisms may also contribute to persistent long COVID symptoms.

Patients admitted with viral respiratory tract infections are at risk ofbacterial co-infections that may exacerbate disease severity. Detection of atypical bacteria requires specific laboratory diagnostic modality and specific antibiotics. In this retrospective regionwide cohort study we included all patients admitted to a hospital in the Central Denmark Region with COVID-19, influenza A, influenza B, or Respiratory Syncytial Virus (RSV) from February 2019 to February 2024. Firstly, we investigated the number of patients testing positive for atypical bacterial co-infection. Secondly, we evaluated associations with diagnostic testing for these atypical bacteria, and the use and associations with administration of empirical treatment with clarithromycin. During the study period a total of 19,651 patients were admitted with one of the viral respiratory tract infections. Only 21 patients tested positive for atypical bacterial co-infection, corresponding to 0.1

ABSTRACT Background Knowledge of the human genetic contribution to the risk of complications from influenza is limited. This study assessed the association between human single‐nucleotide polymorphisms (SNPs) and disease progression in individuals with influenza. Methods A targeted analysis of 10 SNPs with prior evidence in COVID‐19 and a genome‐wide association study (GWAS) were used to assess associations between SNPs and disease progression in two multinational cohorts with suspected or laboratory‐confirmed influenza: a hospitalized cohort (n = 1634) and a pooled cohort of hospitalized and outpatients (n = 3469). Disease progression was defined as prolonged hospitalization (> 28 days), progression to mechanical ventilation, admittance to intensive care unit, or death (for hospitalized individuals) or progression to hospitalization or death (for outpatients). Results Disease progression was observed in 9.1% of hospitalized patients and 2.2% of outpatients. Age was a significant risk factor for disease progression, with 20% increased odds of disease progression per 10‐year increase in age (OR: 1.20, 95%CI: 1.08–1.33, p < 0.001). Disease progression rates also differed by continent (p < 0.0001). Targeted SNP analyses did not identify significant associations with disease progression; however, the strength of associations was most pronounced in sensitivity analyses for the pooled cohort in individuals < 65 years old. GWAS analyses did not identify significant common SNP associations in either the hospitalized or pooled cohorts, nor in sensitivity analysis of (1) individuals with laboratory‐confirmed influenza and (2) those aged < 65 years. Conclusion In a geographically diverse cohort of individuals with influenza, the genetic links to disease progression only started to become evident in the sensitivity analyses, mainly when looking at younger individuals. The power to detect associations was limited by the rate of disease progression and heterogeneity in phenotypes of the individuals studied, and therefore, additional studies focused on the role of genetics in influenza disease progression are needed.

INTRODUCTION:Pyogenic vertebral osteomyelitis (PVO) is a serious bacterial infection of the spinal column, causing significant morbidity and mortality. In this study, we aimed to identify factors associated with functional impairment following a PVO episode and to describe the PVO population in the Central Denmark Region from 2017 to 2023. METHODS:Demographic and clinical data from PVO patients' medical records were collected retrospectively. Functional impairment was defined as a decline in functional status from a higher to a lower level during the PVO episode. Risk analyses for functional impairment were conducted using logistic regression. RESULTS:We identified 472 PVO patients from the Central Denmark Region for the outcome analysis. Median age was 71.5 years, and 66.9% were male. Intraspinal and extraspinal abscesses occurred in 28.4% and 35%, respectively. Staphylococcus aureus was identified in 142/484 patients (29.3%), while a definite microbiological etiology was not established for 137/484 patients (28.3%). Functional impairment occurred in 164/472 patients (34.7%). Age ≥70 years (aOR 5.23; CI: 3.29-8.32), chronic kidney disease (aOR 2.10; CI: 1.07-4.11), cardiovascular disease (aOR 1.95; CI 1.24-3.05) and multifocal spinal involvement (aOR 2.56; CI: 1.15-5.7) were identified as factors associated with an increased risk of functional impairment following PVO, while abscesses (intraspinal or extraspinal) and microbiological factors were not significantly associated with functional impairment. CONCLUSION:In this large cohort of PVO patients, chronic kidney disease, cardiovascular disease, increasing age, and multifocal spinal involvement were associated with functional impairment.

BACKGROUND:The accuracy of recorded diagnosis codes for hospital admissions due to influenza in the Danish national registries is uncertain. We evaluated positive predictive value (PPV) and sensitivity of ICD-10 codes for influenza by comparing to the reference standard of influenza test results. METHODS:Hospital admissions were assessed in the Danish National Patient Registry (DNPR), and influenza test results in the Danish Microbiology Database (MiBa). First, we report the proportion of positive influenza virus tests within seven days of admission among hospital admissions with a discharge influenza ICD-10 code (PPV). Second, we report the proportion with ICD-10 codes for influenza among patients with an admission registered with seven days of a positive influenza virus test (sensitivity). RESULTS:From January 2012 - November 2022 a total of 18,761 admissions were registered with one of the 22 influenza ICD-10 codes in DNPR. Overall, there was a positive influenza test in 16,754 of the admissions (87.9 % = overall PPV, 95 % CI: 87.4-88.3). The PPV was highest for older patient groups (93.7 % in patients >80 years vs. 78.0 % in patients < 11 years), and for admissions that occurred in recent years (95.8 % in 2022 vs. 52.4 % in 2012). Among 33,834 hospitals admissions with a positive influenza test, less than half (n = 16,421, 48.5 % = sensitivity (95 % CI: 48.0 - 49.1 %)) were registered with an influenza ICD-10 code. CONCLUSIONS:ICD-10 diagnoses codes have relatively high positive predictive value, but the sensitivity is low. Furthermore, the PPV depend on age and calendar year. WHAT IS NEW:

Background All-cause and AIDS-mortality in Europe has been decreasing between 1996 and 2020. However, regional differences as well as their drivers remain unclear. This study investigates mortality differences and their drivers, including usage of and response to antiretroviral therapy (ART) and active tuberculosis (TB), among people with HIV across Europe. Methods People with HIV enrolled in EuroSIDA were followed from 2001 through 2020. Immunologic-virologic status (IVS) was categorized as poor (CD4-cell count <= 350 cells/mm(3) and viral load (VL) > 200 copies/ml), good (CD4 >= 500 and VL < 200), or intermediate (remaining combinations). Participants missing either CD4-cell count or VL were categorized as unknown. Regional differences in mortality were analyzed using multivariable Poisson regression with interaction analyses between regions of Europe and IVS, ART, or TB status. Findings 20,364 people with HIV were included: 13,715/20,346 (67.3%) from Western, 3020/20,364 (14.8%) from Central Eastern, and 3629/20,364 (17.8%) from Eastern Europe. At enrolment, median age was 40 years (inter-quartile range (IQR): 33-48), median CD4-cell count 449 cells/mm(3) (IQR: 291-638), and most were male 14,993/20,346 (73.3%). A total of 2639 died during 192,591 person-years of follow-up (crude mortality rate 13.7/1000 person-years, 95% CI: 13.2-14.2), 519/2639 (19.7%) from AIDS (2.7/1000 person-years, 2.5-2.9). All-cause and AIDS-mortality rates decreased over time but remained higher in Eastern Europe after adjusting for confounders. Being off ART (aIRR 2.42; 95% CI 2.14-2.74), poor IVS (aIRR 4.2; 95% CI 3.39-5.20) and prior TB (aIRR 3.33; 95% CI 2.75-4.03) were associated with higher all-cause mortality. For all-cause mortality the effect of ART (test for interaction: p < 0.001) and IVS (p = 0.02), but not TB (p = 0.5) varied across regions. Interpretation Overall mortality and AIDS-mortality rates decreased over time, but remained higher in Eastern Europe. A poor IVS, being off ART and prior active TB were related to higher mortality. Eastern Europe had the highest proportion of people with poor or unknown IVS, emphasizing the continued need to improve HIV care with a focus on early diagnosis, ART initiation, and adherence.

Background Within a year of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, vaccines inducing a robust humoral and cellular immune response were implemented worldwide. However, emergence of novel variants and waning vaccine-induced immunity led to implementation of additional vaccine boosters.Methods This prospective study evaluated the temporal profile of cellular and serological responses in a cohort of 639 SARS-CoV-2-vaccinated participants, of whom a large proportion experienced a SARS-CoV-2 infection. All participants were infection na & iuml;ve at the time of their first vaccine dose. Proportions of SARS-CoV-2 spike-specific T cells were determined after each vaccine dose using the activation-induced marker assay, while levels of circulating SARS-CoV-2 antibodies were determined by the Meso Scale serology assay.Results We found a significant increase in SARS-CoV-2 spike-specific CD4+ and CD8+ T-cell responses following the third dose of a SARS-CoV-2 messenger RNA vaccine as well as enhanced CD8+ T-cell responses after the fourth dose. Furthermore, increased age was associated with a poorer response. Finally, we observed that SARS-CoV-2 infection boosts both the cellular and humoral immune response, relative to vaccine-induced immunity alone.Conclusions Our findings highlight the boosting effect on T-cell immunity of repeated vaccine administration. The combination of multiple vaccine doses and SARS-CoV-2 infections maintains population T-cell immunity, although with reduced levels in the elderly. Cellular and serological responses was evaluated in a cohort of 639 SARS-CoV-2-vaccinated participants. There was a significant increase in SARS-CoV-2 spike-specific T-cell responses following each booster dose. Furthermore, SARS-CoV-2 infection boosts both the cellular and humoral immune response. Graphical Abstract This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/longitudinal-evaluation-of-sars-cov-2-t-cell-immunity-over-2-years-following-vaccination-and-infection?utm_campaign=tidbitlinkshare&utm_source=ITP

Objectives: This study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity. Methods: Danish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day 0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day 90, Day 180, 28 days after 3rd vaccination (Day 251), Day 365, and prior to 4th vaccination (Day 535). SARS-CoV-2 PCR results were extracted from the national microbiology database. Mixed-effect multivariable linear regression investigated the impact of hybrid-immunity (stratified into 4 groups: no hybrid immunity, PCR+ prior to 3rd dose, PCR+ after 3rd dose and before Day 365, PCR+ after Day 365) on anti-spike IgG trajectories. Results: A total of 4,936 individuals were included, 47% developed hybrid-immunity. Anti-spike IgG increases were observed in all groups at Day 251, with the highest levels in those PCR+ prior to 3rd dose (Geometric Mean; 535,647AU/mL vs. 374,665AU/mL with no hybrid-immunity, P<0.0001). Further increases were observed in participants who developed hybrid immunity after their 3rd dose. Anti-spike IgG levels declined from Day 251-535 in individuals without hybrid-immunity and in those who developed hybrid-immunity prior to their 3rd dose, with lower rate of decline in those with hybrid-immunity. Conclusion: Hybrid-immunity results in higher and more durable antibody trajectories in vaccinated individuals.

Despite development of effective SARS-CoV-2 vaccines, a sub-group of vaccine non-responders depends on therapeutic antibodies or small-molecule drugs in cases of severe disease. However, perpetual viral evolution has required continuous efficacy monitoring as well as exploration of new therapeutic antibodies, to circumvent resistance mutations arising in the viral population. We performed SARS-CoV-2-specific B cell sorting and subsequent single-cell sequencing on material from 15 SARS-CoV-2 convalescent participants. Through screening of 455 monoclonal antibodies for SARS-CoV-2 variant binding and virus neutralization, we identified a cluster of activated B cells highly enriched for SARS-CoV-2 neutralizing antibodies. Epitope binning and Cryo-EM structure analysis identified the majority of neutralizing antibodies having epitopes overlapping with the ACE2 receptor binding motif (class 1 binders). Extensive functional antibody characterization identified two potent neutralizing antibodies, one retaining SARS-CoV-1 neutralizing capability, while both bind major common variants of concern and display prophylactic efficacy in vivo. The transcriptomic signature of activated B cells harboring broadly binding neutralizing antibodies with therapeutic potential identified here, may be a guide in future efforts of rapid therapeutic antibody discovery.

Objective: To describe neurophysiological abnormalities cin Long COVID and correlate quantitative elec-tromyography (qEMG) and single fiber EMG (sfEMG) results to clinical scores and histopathology. Methods: 84 patients with non-improving musculoskeletal Long COVID symptoms were examined with qEMG and sfEMG. Muscle biopsies were taken in a subgroup.Results: Mean motor unit potential (MUP) duration was decreased in >= 1 muscles in 52 % of the patients. Mean jitter was increased in 17 % of the patients in tibialis anterior and 25 % in extensor digitorum com-munis. Increased jitter was seen with or without myopathic qEMG. Low quality of life score correlated with higher jitter values but not with qEMG measures. In addition to our previously published mitochon-drial changes, inflammation, and capillary injury, we show now in muscle biopsies damage of terminal nerves and motor endplate with abundant basal lamina material. At the endplate, axons were present but no vesicle containing terminals. The post-synaptic cleft in areas appeared atrophic with short clefts and coarse crests.Conclusions: Myopathic changes are common in Long COVID. sfEMG abnormality is less common but may correlate with clinical scores. sfEMG changes may be due to motor endplate pathology. Significance: These findings may indicate a muscle pathophysiology behind fatigue in Long COVID.(c) 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Abstract Background Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified. Methods In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses. Results Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in individuals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio [GMR] 6.79, 95% confidence interval [CI] 6.05–7.62). Antibody levels were further significantly boosted in all individuals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in individuals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09–1.57) and BA.3 (1.32, 1.09–1.59) antigens in individuals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76–0.98), BA.4 (0.85, 0.75–0.97), and BA.5 (0.87, 0.76–0.99) antigens in individuals with a prior infection. Conclusions Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, suggesting broad cross-protection of Omicron variants.

Abstract Background Side effects to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are a key concern contributing to vaccine hesitancy, but more individuals may be encouraged if SARS-CoV-2 vaccines were known to lead to a stronger immune response. Methods Included were adult participants from the Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 Vaccines (ENFORCE) who completed a questionnaire to assess systemic reactions following SARS-CoV-2 vaccination (BTN162b2, mRNA-1273, ChAdOx1) and had SARS-CoV-2 spike immunoglobulin G (IgG) levels measured at baseline and post–vaccine. A symptom score was developed to measure severity of systemic adverse reactions (+1 for each moderate, +2 for each severe). Post–vaccination SARS-CoV-2 spike IgG levels were compared between participants with different scores using multivariable linear regression. Results A total of 6528 participants were included (56.3% females; median age [interquartile range], 64 [54–75] years). After the first vaccination, no association was found between symptom score and post–vaccine dose spike IgG level (P = .575). Following the second vaccination, significantly higher spike IgG levels were observed according to higher symptom scores (P < .001); adjusted geometric mean ratios were 1.16 (95% CI, 1.04–1.30), 1.24 (95% CI, 1.09–1.41), 1.25 (95% CI, 1.06–1.46), and 1.21 (95% CI, 1.08–1.35), for scores of 2, 3, 4, and ≥5, respectively, compared with a score of 0. After adjustment for pre–vaccine dose spike IgG, this association was attenuated. Conclusions An association was found between more severe adverse reactions and stronger antibody response after the second vaccination but not the first, likely attributed to higher levels of preexisting immunity gained from response to first vaccination. Regardless of side effects, most people experienced an effective immune response following vaccination.

The complement system which is part of the innate immune response against invading pathogens represents a powerful mechanism for killing of infected cells. Utilizing direct complement recruitment for complement-mediated elimination of HIV-1-infected cells is underexplored. We developed a novel therapeutic modality to direct complement activity to the surface of HIV-1-infected cells. This bispecific complement engager (BiCE) is comprised of a nanobody recruiting the complement-initiating protein C1q, and single-chain variable fragments of broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope (Env) protein. Here, we show that two anti-HIV BiCEs targeting the V3 loop and the CD4 binding site, respectively, increase C3 deposition and mediate complement-dependent cytotoxicity (CDC) of HIV-1 Env-expressing Raji cells. Furthermore, anti-HIV BiCEs trigger complement activation on primary CD4 T cells infected with laboratory-adapted HIV-1 strain and facilitates elimination of HIV-1-infected cells over time. In summary, we present a novel approach to direct complement deposition to the surface of HIV-1-infected cells leading to complement-mediated killing of these cells.

Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks ( P = 0.49), 12.5 weeks ( P = 0.003) and 9.5 weeks ( P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756 .

Objectives: Knowledge is limited on how changing SARS-CoV-2 variants may translate into different characteristics and affect the prognosis of patients with long COVID, especially following Omicron variants. We compared long-term prognosis of patients in a Danish Post-COVID Clinic infected with wild-type strain, Alpha, Delta, or Omicron variants as well as the pre-Omicron compared to the Omicron period.Methods: At enrollment, a Post-COVID symptom Questionnaire (PCQ), and standard health scores, were registered and repeated four times until 1.5 years after infection. PCQ was the primary outcome to assess the severity of long COVID, and Delta PCQ to assess failure to improve. Results: A total of 806 patients were enrolled. Patients infected with Omicron and Delta variants presented with more severe long COVID (median PCQ 43 in Delta vs 38 in wild-type, P = 0.003) and health scores (EuroQol five-dimension five-level-index was 0.70 in Omicron vs 0.76 in wild-type, P = 0.009 and 0.78 pre-Omicron, P = 0.006). At 1.5 years after infection, patients had no clinically meaningful decline in severity of long COVID, and 57% (245/429) of patients failed to improve 1.5 years after infection, with no differences between variants.Conclusion: More than half of patients referred to a Post-COVID Clinic failed to improve in long COVID severity 1.5 years after infection regardless of variants of SARS-CoV-2.(c) 2023 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

The aim of this study was to provide information about immunity against COVID-19 along with risk factors and behavior among employees in day care facilities and preschools (DCS) in Denmark. In collaboration with the Danish Union of Pedagogues, during February and March 2021, 47,810 members were offered a point-of-care rapid SARS-CoV-2 antibody test (POCT) at work and were invited to fill in an electronic questionnaire covering COVID-19 exposure. Seroprevalence data from Danish blood donors (total Ig enzyme-linked immunosorbent assay [ELISA]) were used as a proxy for the Danish population. A total of 21,018 (45%) DCS employees completed the questionnaire and reported their POCT result {median age, 44.3 years (interquartile range [IQR], [32.7 to 53.6]); females, 84.1%}, of which 20,267 (96.4%) were unvaccinated and included in analysis. A total of 1,857 (9.2%) participants tested seropositive, significantly higher than a seroprevalence at 7.6% (risk ratio [RR], 1.2; 95% confidence interval [CI], 1.14 to 1.27) among 40,541 healthy blood donors (median age, 42 years [IQR, 28 to 53]; males, 51.3%). Exposure at work (RR, 2.9; 95% CI, 2.3 to 3.6) was less of a risk factor than exposure within the household (RR, 12.7; 95% CI, 10.2 to 15.8). Less than 25% of participants reported wearing face protection at work. Most of the participants expressed some degree of fear of contracting COVID-19 both at work and outside work. SARS-CoV-2 seroprevalence was slightly higher in DCS staff than in blood donors, but possible exposure at home was associated with a higher risk than at work. DCS staff expressed fear of contracting COVID-19, though there was limited use of face protection at work. IMPORTANCE Identifying at-risk groups and evaluating preventive interventions in at-risk groups is imperative for the ongoing pandemic as well as for the control of future epidemics. Although DCS staff have a much higher risk of being infected within their own household than at their workplace, most are fearful of being infected with COVID-19 or bringing COVID-19 to work. This represents an interesting dilemma and an important issue which should be addressed by public health authorities for risk communication and pandemic planning. This study design can be used in a strategy for ongoing surveillance of COVID-19 immunity or other infections in the population. The findings of this study can be used to assess the need for future preventive interventions in DCS, such as the use of personal protective equipment.

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.

SARS-CoV-2 Omicron quickly spread globally, also in regions with high vaccination coverage, emphasizing the importance of exploring the immunological requirements for protection against Omicron breakthrough infection. The test-negative matched case-control study (N = 964) characterized Omicron breakthrough infections in triple-vaccinated individuals from the ENFORCE cohort. Within 60 days before a PCR test spike-specific IgG levels were significantly lower in cases compared to controls (GMR [95% CI] for BA.2: 0.83 [0.73-0.95], p = 0.006). Multivariable logistic regression showed significant associations between high antibody levels and lower odds of infection (aOR [95% CI] for BA.2 spike-specific IgG: 0.65 [0.48-0.88], p = 0.006 and BA.2 ACE2-blocking antibodies: 0.46 [0.30-0.69], p = 0.0002). A sex-stratified analysis showed more pronounced associations for females than males. High levels of vaccine-induced antibodies provide partial protection against Omicron breakthrough infections. This is important knowledge to further characterize a threshold for protection against new variants and to estimate the necessity and timing of booster vaccination.