Subjects who developed SARS-CoV-2 specific IgM after vaccination show a longer humoral immunity and a lower frequency of infection.

BACKGROUND: We have previously shown that eliciting SARS-CoV-2-specific IgM after vaccination is associated with higher levels of SARS-CoV-2 neutralizing IgG. This study aims to assess whether IgM development is also associated with longer-lasting immunity. METHODS: We analysed anti-SARS-CoV-2 spike protein IgG and IgM (IgG-S, IgM-S), and anti-nucleocapsid IgG (IgG-N) in 1872 vaccinees at different time points: before the first dose (D1; w0), before the second dose (D2; w3) at three (w6) and 23 weeks (w29) after D2; moreover, 109 subjects were further tested at the booster dose (D3, w44), at 3 weeks (w47) and 6 months (w70) after D3. Two-level linear regression models were used to evaluate the differences in IgG-S levels. FINDINGS: In subjects who had no evidence of a previous infection at D1 (non-infected, NI), IgM-S development after D1 and D2 was associated with higher IgG-S levels at short (w6, p < 0.0001) and long (w29, p < 0.001) follow-up. Similar IgG-S levels were observed after D3. The majority (28/33, 85%) of the NI subjects who had developed IgM-S in response to vaccination did not experience infection. INTERPRETATION: The development of anti-SARS-CoV-2 IgM-S following D1 and D2 is associated with higher IgG-S levels. Most individuals who developed IgM-S never became infected, suggesting that IgM elicitation may be associated with a lower risk of infection. FUNDING: "Fondi Ricerca Corrente" and "Progetto Ricerca Finalizzata" COVID-2020 (Italian Ministry of Health); FUR 2020 Department of Excellence 2018-2022 (MIUR, Italy); the Brain Research Foundation Verona.

Regulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients.

Background: The host immune response has a prominent role in the progression and outcome of SARS-CoV-2 infection. Lymphopenia has been described as an important feature of SARS-CoV-2 infection and has been associated with severe disease manifestation. Lymphocyte dysregulation and hyper-inflammation have been shown to be associated with a more severe clinical course; however, a T cell subpopulation whose dysfunction correlate with disease progression has yet to be identify. Methods: We performed an immuno-phenotypic analysis of T cell sub-populations in peripheral blood from patients affected by different severity of COVID-19 (n=60) and undergoing a different clinical evolution. Clinical severity was established based on a modified WHO score considering both ventilation support and respiratory capacity (PaO2/FiO2 ratio). The ability of circulating cells at baseline to predict the probability of clinical aggravation was explored through multivariate regression analyses. Results: The immuno-phenotypic analysis performed by multi-colour flow cytometry confirmed that patients suffering from severe COVID-19 harboured significantly reduced circulating T cell subsets, especially for CD4+ T, Th1, and regulatory T cells. Peripheral T cells also correlated with parameters associated with disease severity, i.e., PaO2/FiO2 ratio and inflammation markers. CD4+ T cell subsets showed an important significant association with clinical evolution, with patients presenting markedly decreased regulatory T cells at baseline having a significantly higher risk of aggravation. Importantly, the combination of gender and regulatory T cells allowed distinguishing between improved and worsened patients with an area under the ROC curve (AUC) of 82%. Conclusions: The present study demonstrates the association between CD4+ T cell dysregulation and COVID-19 severity and progression. Our results support the importance of analysing baseline regulatory T cell levels, since they were revealed able to predict the clinical worsening during hospitalization. Regulatory T cells assessment soon after hospital admission could thus allow a better clinical stratification and patient management.

The Impact of the SARS-CoV-2 Outbreak on the Psychological Flexibility and Behaviour of Cancelling Medical Appointments of Italian Patients with Pre-Existing Medical Condition: The "ImpACT-COVID-19 for Patients" Multi-Centre Observational Study.

Psychological distress imposed by the SARS-CoV-2 outbreak particularly affects patients with pre-existing medical conditions, and the progression of their diseases. Patients who fail to keep scheduled medical appointments experience a negative impact on care. The aim of this study is to investigate the psychosocial factors contributing to the cancellation of medical appointments during the pandemic by patients with pre-existing health conditions. Data were collected in eleven Italian hospitals during the last week of lockdown, and one month later. In order to assess the emotional impact of the SARS-CoV-2 outbreak and the subject's degree of psychological flexibility, we developed an ad hoc questionnaire (ImpACT), referring to the Acceptance and Commitment Therapy (ACT) model. The Impact of Event Scale-Revised (IES-R), the Depression, Anxiety and Stress Scale (DASS) and the Cognitive Fusion Questionnaire (CFQ) were also used. Pervasive dysfunctional use of experiential avoidance behaviours (used with the function to avoid thought, emotions, sensations), feelings of loneliness and high post-traumatic stress scores were found to correlate with the fear of COVID-19, increasing the likelihood of cancelling medical appointments. Responding promptly to the information and psychological needs of patients who cancel medical appointments can have positive effects in terms of psychological and physical health.