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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335577

ABSTRACT

Patients with hematological malignancies are prioritized for COVID-19 vaccine due to their high risk for severe SARS-CoV-2 infection related disease and mortality. To understand T cell immunity, its long-term persistence, and correlation with antibody response, we evaluated the BNT162b2 COVID-19 mRNA vaccine-specific immune response in chronic lymphocytic leukemia (CLL) and myeloid dysplastic syndrome (MDS) patients. Longitudinal analysis of CD8 + T cells using DNA-barcoded peptide-MHC multimers covering the full SARS-CoV-2 Spike-protein (415 peptides) showed vaccine-specific T cell activation and persistence of memory T cells up to six months post-vaccination. Surprisingly, a higher frequency of vaccine-induced antigen-specific CD8 + T cell was observed in the patient group compared to a healthy donor group. Furthermore, and importantly, immunization with the second booster dose significantly increased the frequency of antigen-specific CD8 + T cells as well as the total number of T cell specificities. Altogether 59 BNT162b2 vaccine-derived immunogenic epitopes were identified, of which 23 established long-term CD8 + T cell memory response with a strong immunodominance for NYNYLYRLF (HLA-A24:02) and YLQPRTFLL (HLA-A02:01) epitopes. In summary, we mapped the vaccine-induced antigen-specific CD8 + T cells and showed a booster-specific activation and enrichment of memory T cells that could be important for long-term disease protection in this patient group. Key Points COVID-19 mRNA vaccine induced an early and persistent activation of antigen-specific CD8 + T cells in this patient group. Vaccination with a booster dose is required to maintain vaccine-specific CD8 + T cells.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307473

ABSTRACT

COVID-19 pandemic following the outbreak in China and Western Europe, where it finally lost the momentum, is now devastating North and South America. It has not been identified the reason and the molecular mechanisms of the two different patterns of the pulmonary host responses to virus from a minimal disease in young subjects to a severe distress syndrome (ARDS) in older subjects, particularly those with previous chronic diseases (including diabetes) and Cancer. The Management of the Istituto Nazionale Tumori - IRCCS “Fondazione Pascale” in Naples [INT-Pascale], along with all Health professionals decided not to interrupt the treatment of those hospitalized and to continue, even if after a careful triage in order not to allow SARS-CoV-2 positive subjects to access, to take care of cancer patients with serious conditions. Although very few (n=3) patients developed a symptomatic COVID-19 and required the transfer to a COVID-19 area of the Institute, no patients died during the Hospitalization and completed their oncology treatment. Besides monitoring of the patients, all employees of the Institute (physicians, nurses, researchers, lawyers, accountants, gatekeepers, guardians, janitors) have been tested for a possible exposure. Personnel identified as positive, has been promptly subjected to home quarantine and subdued to health surveillance. One severe case of respiratory distress has been reported in a positive employees and one death of a family member. Further steps to home monitoring of COVID-19 clinical course have been taken with the development of remote Wi-Fi connected digital devices for the detection of early signs of respiratory distress, including heart rate and oxygen saturation.In conclusion cancer care has been performed and continued safely also during COVID-19 pandemic and further remote home strategies are in progress to ensure the appropriate monitoring of cancer patients.

3.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328774

ABSTRACT

Background: Both SARS-CoV-2 mRNA-based vaccines [BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)] have shown high efficacy, with very modest side effects in limiting transmission of SARS-CoV-2 and in preventing the severe COVID-19 disease, characterized by a worrying high occupation of intensive care units (ICU), high frequency of intubation and ultimately high mortality rate. At the INT, in Naples, only the BNT162b2 / Pfizer vaccine has been administered to cancer patients and healthcare professionals aged 16 and over.In the present study, the antibody response levels and their decline were monitored in an interval of 6-9 months after vaccine administration in the two different cohorts of workers of the INT - IRCCS "Fondazione Pascale" Cancer Center (Naples, Italy): the group of individuals previously infected with SARS-CoV-2 and vaccinated with a single dose;and that of individuals negative for previous exposure to SARS-CoV-2 vaccinated with two doses 21 days apart. Methods: : Specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S ECLIA immunoassay were determined in serum samples of 27 healthcare workers with a previously documented history of SARS-CoV-2 infection and 123 healthcare workers without, during antibody titers’ monitoring. Moreover, geometric mean titers (GMT) and relative fold changes (FC) were calculated. Results: : Bimodal titer decline was observed in both previously infected and uninfected SARS-CoV-2 subjects. A first rapid decline was followed by a progressive slow decline in the 6/9 month-period before the further vaccine boost. The trend was explained by 2 different mathematical models, exponential and power function, the latter revealing as predictive of antibody titer decline either in infected or in not previously infected ones. The value of the prolonged lower vaccine titer was about 1 log below in the 6/9-month interval after the single dose for previously infected individuals with SARS-CoV-2 and the two doses for those not previously infected. The titer change, after the boost dose administration, on the other hand, was ≥ 1.5 FC higher than the titers at the 6/9-month time-points in both cohorts. A similar quantitative immune titer was observed in both cohorts 8 days after the last boost dose. The subsequent immunoresponse trend remains to be verified. Discussion: The results show that a very rapid first decline, from the highest antibody peak, was followed by a very slow decline which ensured immune protection lasting more than six months. The apparent absence of adverse effects of the rapid decline on the vaccine's immune protective role has been related to a large majority of low avidity antibodies induced by current vaccines. High avidity antibodies with prolonged anti-transmission efficacy show a longer half-life and are lost over a longer interval period. The cellular immunity, capable of preventing severe clinical diseases, lasts much longer. The unbalanced dual activity (cellular vs humoral) while effective in limiting ICU pressure and overall mortality, does not protect against transmission of SARS-CoV-2, resulting in high circulation of the virus among unvaccinated subjects, including the younger population, and the continuous production of variants characterized by changes in transmissibility and pathogenicity. The high mutation rate, peculiar to the RNA virus, can however lead to a dual opposite results: selection of defective and less efficient viruses up to extinction;risk of more efficiently transmitted variants as the current omicron pandemic. Conclusions: : In conclusion the current bimodal antibody-titer decline, following BNT162b2 mRNA anti-SARS-CoV-2 vaccination, needs a further extended analysis to verify the protective borderline levels of immunity and the optimal administration schedule of vaccine boosters. Our current results can contribute to such goal, besides a direct comparison of other FDA-approved and candidate vacci es.

4.
Front Immunol ; 12: 734689, 2021.
Article in English | MEDLINE | ID: covidwho-1354868

ABSTRACT

The response to anti-SARS-Cov-2 preventive vaccine shows high interpersonal variability at short and medium term. One of the explanations might be the individual HLA allelic variants. Indeed, B cell response is stimulated and sustained by CD4+ T helper cells activated by antigens presented by HLA-class II alleles on antigen-presenting cells (APCs). The impact of the number of antigens binding to HLA class-II alleles on the antibody response to the COVID vaccine has been assessed in a cohort of 56 healthcare workers who received the full schedule of the Pfizer-BioNTech BNT162b2 vaccine. Such vaccine is based on the entire spike protein of the SARS-CoV-2. Ab titers have been evaluated 2 weeks after the first dose as well as 2 weeks and 4 months after the boosting dose. HLA-DRB1 and DBQ1 for each of the vaccinees have been assessed, and strong binders have been predicted. The analysis showed no significant correlation between the short-medium-term Ab titers and the number of strong binders (SB) for each individual. These results indicate that levels of Ab response to the spike glycoprotein is not dependent on HLA class II allele, suggesting an equivalent efficacy at global level of the currently used vaccines. Furthermore, the pattern of persistence in Ab titer does not correlate with specific alleles or with the number of SBs.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/immunology , HLA-D Antigens/immunology , SARS-CoV-2/immunology , Antibodies, Viral/immunology , Antibody Affinity/immunology , Antigens, Viral/immunology , COVID-19/prevention & control , Humans , Spike Glycoprotein, Coronavirus/immunology
5.
Infect Agent Cancer ; 15(1): 69, 2020 Nov 23.
Article in English | MEDLINE | ID: covidwho-965787

ABSTRACT

COVID-19 pandemic following the outbreak in China and Western Europe, where it finally lost the momentum, is now devastating North and South America. It has not been identified the reason and the molecular mechanisms of the two different patterns of the pulmonary host responses to the virus from a minimal disease in young subjects to a severe distress syndrome (ARDS) in older subjects, particularly those with previous chronic diseases (including diabetes) and cancer. The Management of the Istituto Nazionale Tumori - IRCCS "Fondazione Pascale" in Naples (INT-Pascale), along with all Health professionals decided not to interrupt the treatment of those hospitalized and to continue, even if after a careful triage in order not to allow SARS-CoV-2 positive subjects to access, to take care of cancer patients with serious conditions. Although very few (n = 3) patients developed a symptomatic COVID-19 and required the transfer to a COVID-19 area of the Institute, no patients died during the hospitalization and completed their oncology treatment. Besides monitoring of the patients, all employees of the Institute (physicians, nurses, researchers, lawyers, accountants, gatekeepers, guardians, janitors) have been tested for a possible exposure. Personnel identified as positive, has been promptly subjected to home quarantine and subdued to health surveillance. One severe case of respiratory distress has been reported in a positive employees and one death of a family member. Further steps to home monitoring of COVID-19 clinical course have been taken with the development of remote Wi-Fi connected digital devices for the detection of early signs of respiratory distress, including heart rate and oxygen saturation.In conclusion cancer care has been performed and continued safely also during COVID-19 pandemic and further remote home strategies are in progress to ensure the appropriate monitoring of cancer patients.

7.
Infect Agent Cancer ; 15: 32, 2020.
Article in English | MEDLINE | ID: covidwho-245089

ABSTRACT

The new human coronavirus named SARS-CoV-2 is a positive-sense RNA virus for which no specific drugs are currently available. A knowledge-based analysis strongly suggests a possible repositioning of the anti-HCV direct antiviral agent (DAA) Sofosbuvir as treatment for SARS-CoV-2. Indeed, the RNA-dependent RNA-polymerases (RdRp) of the two viruses show high sequence and structural homology, supporting the likelihood of binding the Sofosbuvir molecule with similar efficiency. Such a repositioning would allow the containment of the SARS-CoV-2 pandemic and limit the progression of disease to potentially deadly COVID19.

8.
J Transl Med ; 18(1): 185, 2020 05 05.
Article in English | MEDLINE | ID: covidwho-175840

ABSTRACT

A new human coronavirus named SARS-CoV-2 was identified in several cases of acute respiratory syndrome in Wuhan, China in December 2019. On March 11 2020, WHO declared the SARS-CoV-2 infection to be a pandemic, based on the involvement of 169 nations. Specific drugs for SARS-CoV-2 are obviously not available. Currently, drugs originally developed for other viruses or parasites are currently in clinical trials based on empiric data. In the quest of an effective antiviral drug, the most specific target for an RNA virus is the RNA-dependent RNA-polymerase (RdRp) which shows significant differences between positive-sense and negative-sense RNA viruses. An accurate evaluation of RdRps from different viruses may guide the development of new drugs or the repositioning of already approved antiviral drugs as treatment of SARS-CoV-2. This can accelerate the containment of the SARS-CoV-2 pandemic and, hopefully, of future pandemics due to other emerging zoonotic RNA viruses.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Betacoronavirus/enzymology , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , RNA-Dependent RNA Polymerase/antagonists & inhibitors , RNA-Dependent RNA Polymerase/chemistry , Amino Acid Sequence , Betacoronavirus/isolation & purification , COVID-19 , Conserved Sequence , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Drug Repositioning , Humans , Models, Molecular , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , RNA-Dependent RNA Polymerase/metabolism , SARS-CoV-2 , Sequence Alignment , Virus Replication/drug effects , Virus Shedding/drug effects
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