Longitudinal evaluation of SARS-CoV-2 T cell immunity over 2 years following vaccination and infection.

BACKGROUND: Within a year of the 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 naïve 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 Markers (AIM) 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 mRNA vaccine as well as enhanced CD8+ T cell responses after the fourth dose. Further, 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. CONCLUSION: 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.

Humoral immune response to COVID-19 vaccine in patients with myasthenia gravis.

We investigated the humoral response to the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine in patients with myasthenia gravis on or off immunosuppressants and compared this to the response in healthy individuals. The SARS-CoV-2 IgG response and neutralizing capacity were measured in 83 patients (57 on immunosuppressants) and 332 healthy controls at baseline, three weeks, and two and six months after the vaccine. We found that the proportion of positive humoral response was lower in patients on immunosuppressants vs. controls at three weeks and two months (p ≤ 0.001), but not at six months post-vaccination (p = 0.379).

Surveillance of SARS-CoV-2 infection based on self-administered swabs, Denmark, May to July 2022: evaluation of a pilot study.

BackgroundDuring the COVID-19 pandemic, the Danish National Institute for Infectious Disease, Statens Serum Institute (SSI) developed a home-based SARS-CoV-2 surveillance system.AimsWe wanted to determine whether a cohort of individuals performing self-administered swabs for PCR at home could support surveillance of SARS-CoV-2, including detection and assessment of new variants. We also aimed to evaluate the logistical setup.MethodsFrom May to July 2022, 10,000 blood donors were invited to participate, along with their household members. Participation required performing a self-swab for 4 consecutive weeks and answering symptom questionnaires via a web app. Swabs were sent by post to SSI for PCR analysis and whole genome sequencing. After study completion, participants were asked to complete a questionnaire concerning their experience.ResultsIn total, 2,186 individuals enrolled (47.4% blood donors), and 1,333 performed self-swabbing (53.0 blood donors), of whom 48 had at least one SARS-CoV-2-positive sample. Fourteen different Omicron subvariants, primarily BA.5 subvariants, were identified by whole genome sequencing (WGS). In total, 29 of the 63 SARS-CoV-2-positive samples were taken from individuals who were asymptomatic at the time of swabbing. Participants collected 2.9 swabs on average, with varying intervals between swabs. Transmission within households was observed in only three of 25 households.ConclusionParticipants successfully performed self-swabs and answered symptom questionnaires. Also, WGS analysis of samples was possible. The system can support surveillance of respiratory pathogens and also holds potential as a diagnostic tool, easing access to test for at-risk groups, while also reducing the burden on healthcare system resources.

Humoral and cellular immune responses eleven months after the third dose of BNT162b2 an mRNA-based COVID-19 vaccine in people with HIV - a prospective observational cohort study.

BACKGROUND: We investigated long-term durability of humoral and cellular immune responses to third dose of BNT162b2 in people with HIV (PWH) and controls. METHODS: In 378 PWH with undetectable viral replication and 224 matched controls vaccinated with three doses of BNT162b2, we measured IgG-antibodies against the receptor binding domain of SARS-CoV-2 spike protein three months before third dose of BNT162b2, and four and eleven months after. In 178 PWH and 135 controls, the cellular response was assessed by interferon-γ (IFN-γ) release in whole blood four months after third dose. Differences in antibody or IFN-γ concentrations were assessed by uni- and multivariable linear regressions. FINDINGS: Before the third dose the concentration of SARS-CoV-2 antibodies was lower in PWH than in controls (unadjusted geometric mean ratio (GMR): 0.68 (95% CI: 0.54-0.86, p = 0.002). We observed no differences in antibody concentrations between PWH and controls after four (0.90 (95% CI: 0.75-1.09), p = 0.285) or eleven months (0.89 (95% CI: 0.69-1.14), p = 0.346) after the third dose. We found no difference in IFN-γ concentrations four months after the third dose between PWH and controls (1.06 (95% CI: 0.71-1.60), p = 0.767). INTERPRETATION: We found no differences in antibody concentrations or cellular response between PWH and controls up to eleven months after third dose of BNT162b2. Our findings indicate that PWH with undetectable viral replication and controls have comparable immune responses to three doses of the BNT162b2 vaccine. FUNDING: This work was funded by the Novo Nordisk Foundation (NFF205A0063505, NNF20SA0064201), the Carlsberg Foundation (CF20-476 0045), the Svend Andersen Research Foundation (SARF2021), and Bio- and Genome Bank Denmark.

Humoral and cellular immune responses after three or four doses of BNT162b2 in patients with hematological malignancies.

OBJECTIVES: Initial responses to coronavirus disease 2019 vaccination are impaired in patients with hematological malignancies. We investigated immune responses after three or four doses of BNT162b2 in patients with myeloid and lymphoid malignancies compared to controls, and identified risk factors for humoral and cellular nonresponse 1 year after first vaccination. METHODS: In 407 hematological patients (45 myeloid, 362 lymphoid) and 98 matched controls, we measured immunoglobulin G (IgG) and neutralizing antibodies specific for the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at baseline, 3 weeks, 2, 6, and 12 months, and interferon-γ release at 12 months. RESULTS: In patients with lymphoid malignancies, SARS-CoV-2 receptor-binding domain IgG concentration and mean neutralizing capacity was lower than in controls at all time points. A diagnosis of chronic lymphocytic B-cell leukemia (CLL) or lymphoma was associated with humoral nonresponse at 12 months compared to having multiple myeloma/amyloidosis (p < .001 and p = .013). Compared to controls, patients with lymphoid malignancies had increased risk of cellular nonresponse. A lymphoma diagnosis was associated with lower risk of cellular nonresponse compared to patients with multiple myeloma/amyloidosis, while patients with CLL had comparable response rates to patients with multiple myeloma/amyloidosis (p = .037 and p = .280). CONCLUSIONS: In conclusion, long-term humoral and cellular immune responses to BNT162b2 were impaired in patients with lymphoid malignancies.

SARS-CoV-2 antibody dynamics over time and risk factors associated with infection and long COVID-19 symptoms in large working environments.

BACKGROUND: Factors influencing SARS-CoV-2 antibody dynamics, transmission, waning and long COVID-19 symptomatology are still not fully understood. METHODS: In the Danish section of the Novo Nordisk Group, we performed a prospective seroepidemiological study during the first and second waves of the COVID-19 pandemic. All employees and their household members (>18 years) were invited to participate in a baseline (June-August 2020), 6-month follow-up (December 2020-January 2021), and 12-month follow-up (August 2021) sampling. In total, 18,614 accepted and provided at least one blood sample and completed a questionnaire regarding socioeconomic background, health status, previous SARS-CoV-2 infection, and persistent symptoms. Total antibody and specific IgM, IgG and IgA levels against recombinant receptor binding domain were tested. RESULTS: At baseline, the SARS-CoV-2-antibody seroprevalence was 3.9%. At 6-month follow-up, the seroprevalence was 9.1%, while at 12-month follow-up, the seroprevalence was 94.4% (after the vaccine roll-out). Male sex and younger age (18-40 years) were significant risk factors for seropositivity. From baseline to the 6-month sampling, we observed a substantial waning of IgM, IgG and IgA levels (p < 0.001), regardless of age, sex and initial antibody level. An increased antibody level was found in individuals infected prior to vaccination compared to vaccinated infection naïves (p < 0.0001). Approximately a third of the seropositive individuals reported one or more persistent COVID-19 symptoms, with anosmia and/or ageusia (17.5%) and fatigue (15.3%) being the most prevalent. CONCLUSION: The study provides a comprehensive insight into SARS-CoV-2 antibody seroprevalence following infection and vaccination, waning, persistent COVID-19 symptomatology and risk factors for seropositivity in large working environments.

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.

Short-Lived Antibody-Mediated Saliva Immunity against SARS-CoV-2 after Vaccination.

Knowledge about the effect of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on immunity reflected in the saliva is sparse. We examined the antibody response in saliva compared to that in serum 2 and 6 months after the first vaccination with the BNT162b2 vaccine. Four hundred fifty-nine health care professionals were included in a prospective observational study measuring antibody levels in saliva and corresponding serum samples at 2 and 6 months after BNT162b2 vaccination. Vaccinated, previously SARS-CoV-2-infected individuals (hybrid immunity) had higher IgG levels in saliva at 2 months than vaccinated, infection-naive individuals (P < 0.001). After 6 months, saliva IgG levels declined in both groups (P < 0.001), with no difference between groups (P = 0.37). Furthermore, serum IgG levels declined from 2 to 6 months in both groups (P < 0.001). IgG antibodies in saliva and serum correlated in individuals with hybrid immunity at 2 and 6 months (ρ = 0.58, P = 0.001, and ρ = 0.53, P = 0.052, respectively). In vaccinated, infection-naive individuals, a correlation was observed at 2 months (ρ = 0.42, P < 0.001) but not after 6 months (ρ = 0.14, P = 0.055). IgA and IgM antibodies were hardly detectable in saliva at any time point, regardless of previous infection. In serum, IgA was detected at 2 months in previously infected individuals. BNT162b2 vaccination induced a detectable IgG anti-SARS-CoV-2 RBD response in saliva at both 2 and 6 months after vaccination, being more prominent in previously infected than infection-naive individuals. However, a significant decrease in salivary IgG was observed after 6 months, suggesting a rapid decline in antibody-mediated saliva immunity against SARS-CoV-2, after both infection and systemic vaccination. IMPORTANCE Knowledge about the persistence of salivary immunity after SARS-CoV-2 vaccination is limited, and information on this topic could prove important for vaccine strategy and development. We hypothesized that salivary immunity would wane rapidly after vaccination. We measured anti-SARS-CoV-2 IgG, IgA, and IgM concentrations in saliva and serum in both previously infected and infection-naive individuals, 2 and 6 months after first vaccination with BNT162b2, in 459 hospital employees from Copenhagen University Hospital. We observed that IgG was the primary salivary antibody 2 months after vaccination in both previously infected and infection-naive individuals, but dropped significantly after 6 months. Neither IgA nor IgM was detectable in saliva at either time point. Findings indicate that salivary immunity against SARS-CoV-2 rapidly declines following vaccination in both previously infected and infection-naive individuals. We believe this study shines a light on the workings of salivary immunity after SARS-CoV-2 infection, which could prove relevant for vaccine development.

Persistent Symptoms and Sequelae After Severe Acute Respiratory Syndrome Coronavirus 2 Infection Not Requiring Hospitalization: Results From Testing Denmark, a Danish Cross-sectional Survey.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with persistent symptoms ("long COVID"). We assessed the burden of long COVID among nonhospitalized adults with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection. Methods: In the fall of 2020, a cross-sectional survey was performed in the adult Danish general population. This included a self-administered point-of-care test for SARS-CoV-2 antibodies, the Short Form Health Survey (SF-12), and coronavirus disease 2019 (COVID-19)-associated symptom questions. Nonhospitalized respondents with a positive SARS-CoV-2 PCR test ≥12 weeks before the survey (cases) were matched (1:10) to seronegative controls on age, sex, and body mass index. Propensity score-weighted odds ratios (ORs) and ORs for risk factors were estimated for each health outcome. Results: In total, 742 cases and 7420 controls were included. The attributable risk of at least 1 long-COVID symptom was 25.0 per 100 cases (95% confidence interval [CI], 22.2-27.4). Compared to controls, cases reported worse general health (OR, 5.9 [95% CI, 5.0-7.0]) and had higher odds for a broad range of symptoms, particularly loss of taste (OR, 11.8 [95% CI, 9.5-14.6]) and smell (OR, 11.2 [95% CI, 9.1-13.9]). Physical and Mental Component Summary scores were also significantly reduced with differences of -2.5 (95% CI, -3.1 to -1.8) and -2.0 (95% CI, -2.7 to -1.2), respectively. Female sex and severity of initial infection were major risk factors for long COVID. Conclusions: Nonhospitalized SARS-CoV-2 PCR-positive individuals had significantly reduced physical and mental health, and 1 in 4 reported persistence of at least 1 long-COVID symptom.

Waning humoral and cellular immunity after COVID-19 vaccination in patients with psoriasis treated with methotrexate and biologics: a cohort study.

BACKGROUND: mRNA-based COVID-19 vaccines have short- and long-term efficacy in healthy individuals, but their efficacy in patients with psoriasis receiving immunomodulatory therapy is less studied. OBJECTIVES: To investigate long-term immunity after COVID-19 vaccination in patients with psoriasis receiving immunomodulatory therapy. METHODS: A prospective cohort study including patients (n = 123) with psoriasis receiving methotrexate (MTX) or biologics and controls (n = 226). Only mRNA-based COVID-19 vaccines administered with standard intervals between doses were investigated. Markers of immunity included SARS-CoV-2 spike glycoprotein-specific IgG and IgA, neutralizing capacity, and interferon-γ release from T cells stimulated with peptides of the SARS-CoV-2 spike glycoprotein. RESULTS: The proportion of IgG responders was lower 6 months after vaccination in patients receiving anti-tumour necrosis factor (TNF) treatment compared with controls. Anti-TNF treatment was associated with lower IgG levels (ß = -0.82, 95% confidence interval -1.38 to -0.25; P = 0.001). The median neutralizing index was lower in the anti-TNF group [50% inhibition (interquartile range [IQR] 37-89)] compared with controls [98% inhibition (IQR 96-99)]; P < 0.001. Cellular responses were numerically lowest in the anti-TNF group. CONCLUSIONS: Treatment with anti-TNF has an impact on the immunity elicited by mRNA-based COVID-19 vaccination in patients with psoriasis, resulting in a faster waning of humoral and cellular markers of immunity; however, the clinical implications are unknown.

A Cross-Sectional Study of SARS-CoV-2 Antibodies and Risk Factors for Seropositivity in Staff in Day Care Facilities and Preschools in Denmark.

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.

Humoral Immune Responses after an Omicron-Adapted Booster BNT162b2 Vaccination in Patients with Lymphoid Malignancies.

To accommodate waning COVID-19 vaccine immunity to emerging SARS-CoV-2 variants, variant-adapted mRNA vaccines have been introduced. Here, we examine serological responses to the BA.1 and BA.4-5 Omicron variant-adapted BNT162b2 COVID-19 vaccines in people with lymphoid malignancies. We included 233 patients with lymphoid malignancies (chronic lymphocytic B-cell leukemia: 73 (31.3%), lymphoma: 89 (38.2%), multiple myeloma/amyloidosis: 71 (30.5%)), who received an Omicron-adapted mRNA-based COVID-19 vaccine. IgG and neutralizing antibodies specific for the receptor-binding domain (RBD) of SARS-CoV-2 were measured using ELISA-based methods. Differences in antibody concentrations and neutralizing capacity and associations with risk factors were assessed using mixed-effects models. Over the period of vaccination with an Omicron-adapted COVID-19 vaccine, the predicted mean concentration of anti-RBD IgG increased by 0.09 log10 AU/mL/month (95% CI: 0.07; 0.11) in patients with lymphoid malignancies across diagnoses. The predicted mean neutralizing capacity increased by 0.9 percent points/month (95% CI: 0.2; 1.6). We found no associations between the increase in antibody concentration or neutralizing capacity and the variant included in the adapted vaccine. In conclusion, a discrete increase in antibody concentrations and neutralizing capacity was found over the course of Omicron-adapted vaccination in patients with lymphoid malignancies regardless of the adapted vaccine variant, indicating a beneficial effect of Omicron-adapted booster vaccination in this population.

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.

Self-Reported Long COVID and Its Association with the Presence of SARS-CoV-2 Antibodies in a Danish Cohort up to 12 Months after Infection.

The majority of long coronavirus disease (COVID) symptoms are not specific to COVID-19 and could be explained by other conditions. The present study aimed to explore whether Danish individuals with a perception that they suffer from long COVID have antibodies against the nucleocapsid antigen, as a proxy for detecting previous infection. The study was conducted in February and March 2021, right after the second surge of the COVID-19 pandemic in Denmark. All members of the social media group on Facebook "Covidramte med senfølger" ("long COVID sufferers'') above the age of 17 years and living in Denmark were invited to participate in a short electronic questionnaire about long COVID risk factors and symptoms. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein was detected in blood samples as a proxy for natural SARS-CoV-2 infection. The final study population comprised 341 participants (90.6% females) who completed blood sampling and answered the questionnaire. A total of 232 (68%) were seropositive (median age, 49.5 years; interquartile range [IQR], 41 to 55 years; 90.1% females). There was no significant difference between sexes and serostatus. Seronegative and seropositive individuals had a similar burden of symptoms that could be attributed to long COVID. Time since perceived COVID-19 was significantly longer in the group of seronegative individuals than the seropositive ones (P < 0.001). This study suggests that long-COVID sufferers are mostly women and showed that a third of the participants did not have detectable anti-N-protein antibodies. It emphasizes the importance of early confirmation of COVID-19, as this study indicates an overlap between long-COVID symptoms and symptoms that are possibly of another origin. IMPORTANCE This cohort study included questionnaire data as well as anti-nucleocapsid antibody analysis, allowing us to determine whether participants were seropositive due to vaccination or natural infection. The study emphasizes the importance of early confirmation of COVID-19, as antibodies recede with time, and it indicates an overlap between long COVID symptoms and symptoms possibly of another origin.

SARS-CoV-2 Surface Swabs in Locations With Public Access-Potential for Improved Source Control.

The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on surfaces at public locations has been minimally described. By swab testing, we investigated the presence of SARS-CoV-2 on surfaces in public locations during the pandemic in February 2022. The viability of SARS-CoV-2 was not tested. Almost 25% of surfaces were positive for SARS-CoV-2; this was most pronounced in supermarkets.

Levels of SARS-CoV-2 antibodies among fully vaccinated individuals with Delta or Omicron variant breakthrough infections.

SARS-CoV-2 variants of concern have continuously evolved and may erode vaccine induced immunity. In this observational cohort study, we determine the risk of breakthrough infection in a fully vaccinated cohort. SARS-CoV-2 anti-spike IgG levels were measured before first SARS-CoV-2 vaccination and at day 21-28, 90 and 180, as well as after booster vaccination. Breakthrough infections were captured through the Danish National Microbiology database. incidence rate ratio (IRR) for breakthrough infection at time-updated anti-spike IgG levels was determined using Poisson regression. Among 6076 participants, 127 and 364 breakthrough infections due to Delta and Omicron variants were observed. IRR was 0.29 (95% CI 0.15-0.56) for breakthrough infection with the Delta variant, comparing the highest and lowest quintiles of anti-spike IgG. For Omicron, no significant differences in IRR were observed. These results suggest that quantitative level of anti-spike IgG have limited impact on the risk of breakthrough infection with Omicron.

Antibody responses and risk factors associated with impaired immunological outcomes following two doses of BNT162b2 COVID-19 vaccination in patients with chronic pulmonary diseases.

INTRODUCTION: Responses to COVID-19 vaccination in patients with chronic pulmonary diseases are poorly characterised. We aimed to describe humoral responses following two doses of BNT162b2 mRNA COVID-19 vaccine and identify risk factors for impaired responses. METHODS: Prospective cohort study including adults with chronic pulmonary diseases and healthcare personnel as controls (1:1). Blood was sampled at inclusion, 3 weeks, 2 and 6 months after first vaccination. We reported antibody concentrations as geometric means with 95% CI of receptor binding domain (RBD)-IgG and neutralising antibody index of inhibition of ACE-2/RBD interaction (%). A low responder was defined as neutralising index in the lowest quartile (primary outcome) or RBD-IgG <225 AU/mL plus neutralising index <25% (secondary outcome), measured at 2 months. We tested associations using Poisson regression. RESULTS: We included 593 patients and 593 controls, 75% of all had neutralising index ≥97% at 2 months. For the primary outcome, 34.7% of patients (n=157/453) and 12.9% of controls (n=46/359) were low responders (p<0.0001). For the secondary outcome, 8.6% of patients (n=39/453) and 1.4% of controls (n=5/359) were low responders (p<0.001). Risk factors associated with low responder included increasing age (per decade, adjusted risk ratio (aRR) 1.17, 95% CI 1.03 to 1.32), Charlson Comorbidity Index (per point) (aRR 1.15, 95% CI 1.05 to 1.26), use of prednisolone (aRR 2.08, 95% CI 1.55 to 2.77) and other immunosuppressives (aRR 2.21, 95% CI 1.65 to 2.97). DISCUSSION: Patients with chronic pulmonary diseases established functional humoral responses to vaccination, however lower than controls. Age, comorbidities and immunosuppression were associated with poor immunological responses.

SARS-CoV-2 antibody prevalence among homeless people and shelter workers in Denmark: a nationwide cross-sectional study.

BACKGROUND: People experiencing homelessness (PEH) and associated shelter workers may be at higher risk of infection with "Severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). The aim of this study was to determine the prevalence of SARS-CoV-2 among PEH and shelter workers in Denmark. DESIGN AND METHODS: In November 2020, we conducted a nationwide cross-sectional seroprevalence study among PEH and shelter workers at 21 recruitment sites in Denmark. The assessment included a point-of-care test for antibodies against SARS-CoV-2, followed by a questionnaire. The seroprevalence was compared to that of geographically matched blood donors considered as a proxy for the background population, tested using a total Ig ELISA assay. RESULTS: We included 827 participants in the study, of whom 819 provided their SARS-CoV-2 antibody results. Of those, 628 were PEH (median age 50.8 (IQR 40.9-59.1) years, 35.5% female) and 191 were shelter workers (median age 46.6 (IQR 36.1-55.0) years and 74.5% female). The overall seroprevalence was 6.7% and was similar among PEH and shelter workers (6.8% vs 6.3%, p = 0.87); and 12.2% among all participants who engaged in sex work. The overall participant seroprevalence was significantly higher than that of the background population (2.9%, p < 0.001). When combining all participants who reported sex work or were recruited at designated safe havens, we found a significantly increased risk of seropositivity compared to other participants (OR 2.23, 95%CI 1.06-4.43, p = 0.02). Seropositive and seronegative participants reported a similar presence of at least one SARS-CoV-2 associated symptom (49% and 54%, respectively). INTERPRETATIONS: The prevalence of SARS-CoV-2 antibodies was more than twice as high among PEH and associated shelter workers, compared to the background population. These results could be taken into consideration when deciding in which phase PEH are eligible for a vaccine, as part of the Danish national SARS-CoV-2 vaccination program rollout. FUNDING: TrygFonden and HelseFonden.

Decline in Antibody Concentration 6 Months After Two Doses of SARS-CoV-2 BNT162b2 Vaccine in Solid Organ Transplant Recipients and Healthy Controls.

Background: Previous studies have indicated inferior responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients. We examined the development of anti-receptor-binding domain (RBD) immunoglobulin G (IgG) after two doses of BNT162b2b in SOT recipients 6 months after vaccination and compared to that of immunocompetent controls. Methods: We measured anti-RBD IgG after two doses of BNT162b2 in 200 SOT recipients and 200 matched healthy controls up to 6 months after first vaccination. Anti-RBD IgG concentration and neutralizing capacity of antibodies were measured at first and second doses of BNT162b2 and 2 and 6 months after the first dose. T-cell responses were measured 6 months after the first dose. Results: In SOT recipients, geometric mean concentration (GMC) of anti-RBD IgG increased from first to second dose (1.14 AU/ml, 95% CI 1.08-1.24 to 11.97 AU/ml, 95% CI 7.73-18.77) and from second dose to 2 months (249.29 AU/ml, 95% CI 153.70-385.19). Six months after the first vaccine, anti-RBD IgG declined (55.85 AU/ml, 95% CI 36.95-83.33). At all time points, anti-RBD IgG was lower in SOT recipients than that in controls. Fewer SOT recipients than controls had a cellular response (13.1% vs. 59.4%, p < 0.001). Risk factors associated with humoral non-response included age [relative risk (RR) 1.23 per 10-year increase, 95% CI 1.11-1.35, p < 0.001], being within 1 year from transplantation (RR 1.55, 95% CI 1.30-1.85, p < 0.001), treatment with mycophenolate (RR 1.54, 95% CI 1.09-2.18, p = 0.015), treatment with corticosteroids (RR 1.45, 95% CI 1.10-1.90, p = 0.009), kidney transplantation (RR 1.70, 95% CI 1.25-2.30, p = 0.001), lung transplantation (RR 1.63, 95% CI 1.16-2.29, p = 0.005), and de novo non-skin cancer comorbidity (RR 1.52, 95% CI, 1.26-1.82, p < 0.001). Conclusion: Immune responses to BNT162b2 are inferior in SOT recipients compared to healthy controls, and studies aiming to determine the clinical impact of inferior vaccine responses are warranted.