Clinical and Immunological Features of SARS-CoV-2 Breakthrough Infections in Vaccinated Individuals Requiring Hospitalization
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Abstract
Background and Purpose
Waning immunity and the surge of SARS-CoV-2 variants are responsible for breakthrough infections, i.e., infections in fully vaccinated individuals. Although the majority of vaccinated infected subjects report mild or no symptoms, some others require hospitalization. The clinical and immunological features of vaccinated hospitalized COVID-19 patients are currently unknown.
Methods
Twenty-nine unvaccinated and 36 vaccinated hospitalized COVID-19 patients were prospectively enrolled and clinical and laboratory data were gathered. Immunophenotyping of leukocytes’ subsets, T and B cell SARS-CoV-2-specific responses were evaluated via flow cytometry. Anti-IFN-α autoantibodies were measured via ELISA.
Results
Despite vaccinated patients were older and with more comorbidities, unvaccinated subjects showed higher levels of pro-inflammatory markers, more severe disease, and increased mortality rate. Accordingly, they presented significant alterations in the circulating leukocyte composition, typical of severe COVID-19. Vaccinated patients displayed higher levels of anti-Spike IgGs and Spike-specific B cells. Of all participants, survivors showed higher levels of anti-Spike IgGs and Spike-specific CD4+ T cells than non-survivors. At hospital admission, 6 out of 65 patients (9.2%) displayed high serum concentrations of autoantibodies targeting IFN-α. Remarkably, 3 were unvaccinated and eventually died, while the other 3 were vaccinated and survived.
Conclusion
Despite more severe pre-existing clinical conditions, vaccinated patients have good outcome. A rapid activation of anti-SARS-CoV-2-specific immunity is fundamental for the resolution of the infection. Therefore, prior immunization through vaccination provides a significant contribution to prevention of disease worsening and can even overcome the presence of high-risk factors (i.e., older age, comorbidities, anti-IFN-α autoantibodies).
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SciScore for 10.1101/2022.02.14.22270857: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Study approval: The procedures followed in the study were approved by the Careggi University Hospital Ethical Committee.
Consent: Written informed consent was obtained from recruited patients.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Evaluation of SARS-CoV-2-specific IgM and IgG: Evaluation of anti-Spike protein (in trimeric form) IgG (Diasorin); anti-Spike protein IgM (Abbot), anti-Nucleoprotein IgG (Abbott), neutralizing antibodies which block binding of Spike protein with the ACE2 receptorAb (Dia.Pro Diagnostic Bioprobes) was performed following manufacturers’s … SciScore for 10.1101/2022.02.14.22270857: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Study approval: The procedures followed in the study were approved by the Careggi University Hospital Ethical Committee.
Consent: Written informed consent was obtained from recruited patients.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Evaluation of SARS-CoV-2-specific IgM and IgG: Evaluation of anti-Spike protein (in trimeric form) IgG (Diasorin); anti-Spike protein IgM (Abbot), anti-Nucleoprotein IgG (Abbott), neutralizing antibodies which block binding of Spike protein with the ACE2 receptorAb (Dia.Pro Diagnostic Bioprobes) was performed following manufacturers’s instructions. anti-Spike protein (in trimeric form) IgGsuggested: Noneanti-Spike protein IgMsuggested: Noneanti-Nucleoprotein IgGsuggested: NoneFlow cytometry experiments were performed using published guidelines (Cossarizza et al., 2021) Measurement of Human Anti-IFN-α antibodies: Titres of anti-IFN-α antibodies were measured via enzyme-linked immunosorbent assay (Invitrogen) on patients’ sera, according to manufacturer’s instructions. Anti-IFN-αsuggested: NoneSoftware and Algorithms Sentences Resources Samples were acquired on a BD LSR II flow cytometer (BD Biosciences) and analysed with FlowJo v10 software. FlowJosuggested: (FlowJo, RRID:SCR_008520)Cultures were performed in medium alone (background, negative control), with a pool of Spike SARS-CoV-2 peptide pools (Prot_S1, Prot_S+ and Prot_S to achieve a complete sequence coverage of the Spike protein), or with a pool of peptide pools covering nucleoprotein and membrane protein. Prot_Ssuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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