Durable spike-specific T-cell responses after different COVID-19 vaccination regimens are not further enhanced by booster vaccination.

Several COVID-19 vaccines are approved to prevent severe disease outcome following SARS-CoV-2 infection. Whereas the induction and functionality of anti-viral antibody response is largely studied, the induction of T cells upon vaccination with the different approved COVID-19 vaccines is less studied. Here, we reported on T-cell immunity four weeks and six months after different vaccination regimens and four weeks after an additional booster vaccination, in comparison to SARS-CoV-2 T-cell responses in convalescents and prepandemic donors using interferon-gamma ELISpot assays and flow cytometry. Increased T-cell responses and cross-recognition of B.1.1.529 Omicron variant-specific mutations were observed ex vivo in mRNA- and heterologous-vaccinated donors compared to vector-vaccinated donors. Nevertheless, potent expandability of T cells targeting the spike protein was observed for all vaccination regimens with frequency, diversity and the ability to produce several cytokines of vaccine-induced T-cell responses comparable to those in convalescent donors. T-cell responses for all vaccinated donors significantly exceeded preexisting cross-reactive T-cell responses in prepandemic donors. Booster vaccination led to a significant increase of anti-spike IgG responses, which showed a marked decline 6 month after complete vaccination. In contrast, T-cell responses remained stable over time following complete vaccination with no significant effect of booster vaccination on T-cell responses and cross-recognition of Omicron BA.1 and BA.2 mutations.This suggested that booster vaccination is of particular relevance for the amelioration of antibody response. Together, our work shows that different vaccination regimens induce broad and long-lasting spike-specific CD4+ and CD8+ T-cell immunity to SARS-CoV-2.

A Quantitative ELISA to Detect Anti-SARS-CoV-2 Spike IgG Antibodies in Infected Patients and Vaccinated Individuals.

There is an ongoing need for high-precision serological assays for the quantitation of anti-SARS-CoV-2 antibodies. Here, a trimeric SARS-CoV-2 spike (S) protein was used to develop an ELISA to quantify specific IgG antibodies present in serum, plasma, and dried blood spots (DBS) collected from infected patients or vaccine recipients. The quantitative S-ELISA was calibrated with international anti-SARS-CoV-2 immunoglobulin standards to provide test results in binding antibody units per mL (BAU/mL). The assay showed excellent linearity, precision, and accuracy. A sensitivity of 100% was shown for samples collected from 54 patients with confirmed SARS-CoV-2 infection more than 14 days after symptom onset or disease confirmation by RT-PCR and 58 vaccine recipients more than 14 days after vaccination. The assay specificity was 98.3%. Furthermore, antibody responses were measured in follow-up samples from vaccine recipients and infected patients. Most mRNA vaccine recipients had a similar response, with antibody generation starting 2-3 weeks after the first vaccination and maintaining positive for at least six months after a second vaccination. For most infected patients, the antibody titers increased during the second week after PCR confirmation. This S-ELISA can be used to quantify the seroprevalence of SARS-CoV-2 in the population exposed to the virus or vaccinated.

Feeling lonely during the pandemic: Towards personality-tailored risk profiles.

This is the first study to disentangle associations of within- and between-person fluctuations in loneliness and their effect on evening mood during a nationwide lockdown due to COVID-19. To contribute to the development of personality-tailored risk profiles, we additionally explored the moderating role of trait neuroticism and extraversion on the association of within- and between-person loneliness and mood. We employed an ambulatory assessment design during 21 days of nationwide lockdown in Germany (13/04/2020-03/05/2020) with two interval-based assessments. The final sample comprised 322 participants (74.5% women) aged between 15 and 82 years (M = 30.7, SD = 14.9) providing 6,084 evening assessments. Linear mixed models were used to evaluate the effects of within- and between-person fluctuations in loneliness on evening mood while controlling for unspecific effects of time, sex, and age. Moderation analysis was used to investigate the influence of neuroticism and extraversion on the relation between loneliness and mood, respectively. Results indicate that especially higher between-person loneliness (i.e. participants felt lonelier compared to the average participant) but also higher within-person loneliness (i.e. participants felt lonelier compared to their individual mean) were associated with a more unpleasant mood. Neuroticism augmented the effect of within-person loneliness, while extraversion seemed to buffer the effect of between-person loneliness on mood. Our findings underline the importance of carefully monitoring loneliness during COVID-19. The findings contribute towards the development of personality-tailored risk profiles (e.g. among newly arising risk groups for loneliness due to COVID-19). We discuss how the differential consideration of within- and between-psychological processes might help to elucidate currently mixed findings on psychological coping during the COVID-19 pandemic.

A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity.

T cell immunity is central for the control of viral infections. CoVac-1 is a peptide-based vaccine candidate, composed of SARS-CoV-2 T cell epitopes derived from various viral proteins1,2, combined with the Toll-like receptor 1/2 agonist XS15 emulsified in Montanide ISA51 VG, aiming to induce profound SARS-CoV-2 T cell immunity to combat COVID-19. Here we conducted a phase I open-label trial, recruiting 36 participants aged 18-80 years, who received a single subcutaneous CoVac-1 vaccination. The primary end point was safety analysed until day 56. Immunogenicity in terms of CoVac-1-induced T cell response was analysed as the main secondary end point until day 28 and in the follow-up until month 3. No serious adverse events and no grade 4 adverse events were observed. Expected local granuloma formation was observed in all study participants, whereas systemic reactogenicity was absent or mild. SARS-CoV-2-specific T cell responses targeting multiple vaccine peptides were induced in all study participants, mediated by multifunctional T helper 1 CD4+ and CD8+ T cells. CoVac-1-induced IFNγ T cell responses persisted in the follow-up analyses and surpassed those detected after SARS-CoV-2 infection as well as after vaccination with approved vaccines. Furthermore, vaccine-induced T cell responses were unaffected by current SARS-CoV-2 variants of concern. Together, CoVac-1 showed a favourable safety profile and induced broad, potent and variant of concern-independent T cell responses, supporting the presently ongoing evaluation in a phase II trial for patients with B cell or antibody deficiency.

Negative Emotion Differentiation Attenuates the Within-Person Indirect Effect of Daily Stress on Nightly Sleep Quality Through Calmness.

The ability to differentiate between negative emotional states [negative emotion differentiation (NED)] has been conceptualized as a trait that facilitates effective emotion regulation and buffers stress reactivity. In the present research, we investigated the role of NED in within-person processes of daily affect regulation and coping during times of stress (the first COVID-19-related pandemic lockdown in April 2020). Using intensive longitudinal data, we analyzed whether daily stress had an indirect effect on sleep quality through calmness in the evening, and we tested whether NED moderated this within-person indirect effect by buffering the link between daily stress and calmness in the evening. A non-representative community sample (n = 313, 15-82 years old) participated in a 21-day ambulatory assessment with twice-daily surveys. The results of multilevel mediation models showed that higher daily stress was related to within-day change in calmness from morning to evening, resulting in less calmness in the evening within persons. Less calmness in the evening, in turn, was related to poorer nightly sleep quality within persons. As expected, higher NED predicted a less negative within-person link between daily stress and calmness in the evening, thereby attenuating the indirect effect of daily stress on nightly sleep quality through calmness. This effect held when we controlled for mean negative emotions and depression. The results provide support for a diathesis-stress model of NED, and hence, for NED as a protective factor that helps to explain why some individuals remain more resilient during times of stress than others.

Coping under a COVID-19 lockdown: patterns of daily coping and individual differences in coping repertoires.

BACKGROUND: Polyregulation-the concurrent or sequential use of multiple strategies to regulate affect or cope with stressors-is a frequent but understudied phenomenon. OBJECTIVES: We aimed to identify patterns of daily coping and individuals' coping repertoires (i.e., range of coping patterns employed across situations) during a COVID-19 pandemic lockdown. We investigated day-level covariates (appraisals, worrying, mood) of daily coping patterns and person-level covariates (psychopathology, average mood) of coping repertoires. Design: A non-representative community sample (n = 322, 15-82 years old) participated in a 21-day ambulatory assessment study. METHODS: We applied multilevel latent class analysis.. RESULTS: We identified seven daily coping patterns and ten classes of individuals differing in the size of their coping repertoire and their propensity for polyregulation. Daily coping patterns differed in daily perceived controllability and mood (but not in daily worrying or stress). At the person level, individuals with a higher level of average coronavirus-related worrying more frequently engaged in a high degree of polyregulation. The size of individuals' coping repertoire was unrelated to psychopathology and average mood. CONCLUSION: The findings provide insights into the composition of daily coping patterns and individuals' coping repertoires during crisis periods and contribute to a new polyregulation perspective on coping.

SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition.

T cell immunity is central for the control of viral infections. To characterize T cell immunity, but also for the development of vaccines, identification of exact viral T cell epitopes is fundamental. Here we identify and characterize multiple dominant and subdominant SARS-CoV-2 HLA class I and HLA-DR peptides as potential T cell epitopes in COVID-19 convalescent and unexposed individuals. SARS-CoV-2-specific peptides enabled detection of post-infectious T cell immunity, even in seronegative convalescent individuals. Cross-reactive SARS-CoV-2 peptides revealed pre-existing T cell responses in 81% of unexposed individuals and validated similarity with common cold coronaviruses, providing a functional basis for heterologous immunity in SARS-CoV-2 infection. Diversity of SARS-CoV-2 T cell responses was associated with mild symptoms of COVID-19, providing evidence that immunity requires recognition of multiple epitopes. Together, the proposed SARS-CoV-2 T cell epitopes enable identification of heterologous and post-infectious T cell immunity and facilitate development of diagnostic, preventive and therapeutic measures for COVID-19.