Robust and Persistent B- and T-Cell Responses after COVID-19 in Immunocompetent and Solid Organ Transplant Recipient Patients.

The development and persistence of SARS-CoV-2-specific immune response in immunocompetent (IC) and immunocompromised patients is crucial for long-term protection. Immune response to SARS-CoV-2 infection was analysed in 57 IC and 15 solid organ transplanted (TX) patients. Antibody responses were determined by ELISA and neutralization assay. T-cell response was determined by stimulation with peptide pools of the Spike, Envelope, Membrane, and Nucleocapsid proteins with a 20-h Activation Induced Marker (AIM) and 7-day lymphoproliferative assays. Antibody response was detected at similar levels in IC and TX patients. Anti-Spike IgG, IgA and neutralizing antibodies persisted for at least one year, while anti-Nucleocapsid IgG declined earlier. Patients with pneumonia developed higher antibody levels than patients with mild symptoms. Similarly, both rapid and proliferative T-cell responses were detected within the first two months after infection at comparable levels in IC and TX patients, and were higher in patients with pneumonia. T-cell response persisted for at least one year in both IC and TX patients. Spike, Membrane, and Nucleocapsid proteins elicited the major CD4+ and CD8+ T-cell responses, whereas the T-cell response to Envelope protein was negligible. After SARS-CoV-2 infection, antibody and T-cell responses develop rapidly and persist over time in both immunocompetent and transplanted patients.

Humoral and cell-mediated response against SARS-CoV-2 variants elicited by mRNA vaccine BNT162b2 in healthcare workers: a longitudinal observational study.

OBJECTIVES: To assess the humoral and cell-mediated response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicited by the mRNA BNT162b2 vaccine in SARS-CoV-2-experienced and -naive subjects against a reference strain and SARS-CoV-2 variants. METHODS: The humoral response (including neutralizing antibodies) and T-cell-mediated response elicited by BNT162b2 vaccine in 145 healthcare workers (both naive and positive for previous SARS-CoV-2 infection) were evaluated. In a subset of subjects, the effect of SARS-CoV-2 variants on antibody level and cell-mediated response was also investigated. RESULTS: Overall, 125/127 naive subjects (98.4%) developed both neutralizing antibodies and specific T cells after the second dose of vaccine. Moreover, the antibody and T-cell responses were effective against viral variants since SARS-CoV-2 NT Abs were still detectable in 55/68 (80.9%) and 25/29 (86.2%) naive subjects when sera were challenged against ß and δ variants, respectively. T-cell response was less affected, with no significant difference in the frequency of responders (p 0.369). Of note, two doses of vaccine were able to elicit sustained neutralizing antibody activity against all the SARS-CoV-2 variants tested in SARS-CoV-2-experienced subjects. CONCLUSIONS: BNT162b2 vaccine elicited a sustained humoral and cell-mediated response in immunocompetent subjects after two-dose administration of the vaccine, and the response seemed to be less affected by SARS-CoV-2 variants, the only exceptions being the ß and δ variants. Increased immunogenicity, also against SARS-CoV-2 variant strains, was observed in SARS-CoV-2-experienced subjects. These results suggest that triple exposure to SARS-CoV-2 antigens might be proposed as valuable strategy for vaccination campaigns.

Analysis of the SARS-CoV-2 epidemic in Italy: The role of local and interventional factors in the control of the epidemic.

Containment measures have been applied in several countries in order to limit the diffusion of the SARS-CoV-2 epidemic. The scope of this study is to analyze the evolution of the first wave of the SARS-CoV-2 epidemic throughout Italy and factors associated to the different way it spread in the Italian Regions, starting from the day that the first indigenous cases were detected through day 81 (6 days after the end of the strict lockdown). Data were obtained from daily reports and are represented as number (and percentage) of cases/100,000 persons. A lockdown with movement restrictions, especially across Regions, was declared at day 20. At day 81, 219,070 cases (363/100,000 persons) were diagnosed. A regression analysis based on the Gompertz model predicts a total number 233,606 cases (386/100,000 persons) at the end of the epidemic. The 21 areas, divided into Italian Regions and autonomous Provinces, showed a wide range in the frequency of cases at day 81 (58-921, median 258/100,000 persons) and total predicted cases (58-946, median 267/100,000 persons). Similarly, the predicted time for the end of the wave of the epidemic (considering as surrogate marker the time at which 99% of the total cases are predicted to occur) was highly variable, ranging from 64 to 136 (median 99) days. We analyzed the impact of local and interventional variables on the epidemic curve in each Region. The number of cases correlated inversely with the distance from the area in which first cases were detected and directly also with the gross domestic product pro capite (as a marker of industrial activity) of the Region. Moreover, an earlier start of the lockdown (i.e. in the presence of a lower number of cases) and wider testing were associated with a lower final number of total cases. In conclusion, this analysis shows that population-wide testing and early lockdown enforcement appear effective in limiting the spreading of the SARS-CoV-2 epidemic.

Neutrophil Extracellular Traps Induce the Epithelial-Mesenchymal Transition: Implications in Post-COVID-19 Fibrosis.

The release of neutrophil extracellular traps (NETs), a process termed NETosis, avoids pathogen spread but may cause tissue injury. NETs have been found in severe COVID-19 patients, but their role in disease development is still unknown. The aim of this study is to assess the capacity of NETs to drive epithelial-mesenchymal transition (EMT) of lung epithelial cells and to analyze the involvement of NETs in COVID-19. Bronchoalveolar lavage fluid of severe COVID-19 patients showed high concentration of NETs that correlates with neutrophils count; moreover, the analysis of lung tissues of COVID-19 deceased patients showed a subset of alveolar reactive pneumocytes with a co-expression of epithelial marker and a mesenchymal marker, confirming the induction of EMT mechanism after severe SARS-CoV2 infection. By airway in vitro models, cultivating A549 or 16HBE at air-liquid interface, adding alveolar macrophages (AM), neutrophils and SARS-CoV2, we demonstrated that to trigger a complete EMT expression pattern are necessary the induction of NETosis by SARS-CoV2 and the secretion of AM factors (TGF-ß, IL8 and IL1ß). All our results highlight the possible mechanism that can induce lung fibrosis after SARS-CoV2 infection.