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Background Since the outbreak of COVID-19 pandemic the scientific community efforts have been focused on finding a vaccine and a treatment for infected people. Several antivirals with activity against SARS-CoV-2 were investigated and since the end of 2021 orally administered antivirals have been used in positive patients. Methods We conducted a retrospective, single-center study including data from 135 outpatients who resulted positive for SARS-CoV-2 and were selected according to AIFA criteria to receive Molnupiravir (M) or Nirmatrelvir/Ritonavir (N/R) in the Infectious Disease Clinic of the Tor Vergata Hospital from January 2022 to February 2022. Results Our cohort included 135 patients with a median age of 71 years (IQR 56,5 – 80,5), 51% were male, 91% received M and 9% received N/R. The median time of antiviral administration from symptoms onset was of 3,4 days. 75% of patients were vaccinated with booster dose, 19% were vaccinated with two doses and 7% were unvaccinated. The most frequent criteria of eligibility are summarized in Figure 1. Only 2 patients were hospitalized receiving oxygen support, 1 patient died, 84% of patients did not need hospitalization and 14% of the enrolled subjects were lost at follow up. Time of negativization at the nasopharyngeal swab (NPS) had a negative correlation to the value of anti-Spike (r=-0.29; p=0.01). The difference between cycle threshold (Ct) value of NPS at T7 and Ct value at the first positive NPS (T0) was higher among not hospitalized (NH) vs hospitalized (H) patients, for Gene E [12.1 (SD 5.8) vs -1.7 (SD 10.8); p=0.02], Gene N [12.3 (SD 10.8) vs -0.9 (SD 11.6); p=0.01] and Gene RdRp [11.8 (SD 5.3) vs -1.5 (SD 11.1); p=0.01]. Anti-Spike were higher among NH vs H patients [1714 (SD 1044.7) vs [43 (SD 60.3); p=0.028]. Delta Ct E, delta Ct N and delta Ct RdRp were significantly higher in patients without neoplastic disease (p=0.04, p=0.02, p=0.01, respectively) and had a negative correlation with creatinine levels (r=-0.36, p< 0.001; r=-0.3, p=0.03; r=-0.32, p=0.02). Percentage of eligibility criteria of our patients The majority of patients had more than one criterion Conclusion Oral antivirals represent a new effective treatment against COVID-19 in selected patients, reducing the time of negativization and the risk of hospitalization and death. Solid tumor or oncohematologic diseases are associated to a slower negativization of NPS. Disclosures All Authors: No reported disclosures.

Background Cell-mediated immunity (CMI) after anti-Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 vaccines has been poorly explored in recipients of allogeneic hematopoietic stem-cell transplantation (HSCT), especially with regard to the 3rd dose (booster). Aim of the study was to assess the specific T-cell responses before and after the 3rd dose of BNT162b2 mRNA vaccine in a cohort of allogeneic HSCT recipients, and compare it with healthy donors (HD). Methods Allogenic HSCT recipients and HD were enrolled before receiving the 3rd dose of BNT162b2 mRNA vaccine. Whole blood for T-cell specific responses was collected before (T1) and 8 weeks after (T2) the booster administration. T-cell responses were assessed with an Interferon (IFN)-γ release assay (IGRA), after overnight stimulation of heparin whole blood with pools of lyophilized peptides, covering the immunodominant sequence of the Spike (S) protein. IFN-γ production was assessed with an enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed with GraphPadPrism. Results 14 HSCT recipients (8M, 6F) and 15 HD (7M, 8F) were enrolled (table 1). Median age was 47 [39-59] and 41 [31-48] years in the HSCT and HD groups, respectively. Time between the vaccine 2nd dose and T1 was significantly longer in HD than HSCT recipients (p< .001), while the time between T1 and T2 did not differ between the two groups. SARS-CoV-2 S specific T-cell responses at T1 were inferior in HSCT recipients compared to HD (median IFN-γ production: 463 vs 231 ng/ml, respectively), although the difference did not reach the statistical significance. No differences were observed at T2. In a before-after analysis, SARS-CoV-2 S specific T-cell responses were significantly increased in HSCT recipients at T2 compared to T1 (median IFN-γ production: 267 vs 881 ng/ml, p=0.02) (Figure 1). At T1, 3 HSCT recipients showed very low or no IFN-γ production, while at T2 only 1 patient still had undetectable IFN-γ production after S peptide stimulation. Table 1:Clinical characteristics of allo-HSCT recipients and HDHSCT: hematopoietic stem-cell transplantation; IQR: interquartile range; ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; MDS: myelodysplastic syndrome; T-ALL: T-cell acute lymphoblastic leukemia; AA: aplastic anemia; PMF: primary myelofibrosis; MUD: matched unrelated donor; MMUD: mismatched unrelated donors; NA: not applicable; ns: not significant.Figure 1:IFN-γ Production after Spike peptide stimulation of whole blood from allogenic HSCT recipients and HD.Comparison of IFN-γ production after Spike peptide stimulation of whole blood in allogenic HSCT recipients and HD at T1 (1.A) and T2 (1.B) (before and after BNT162b2 mRNA vaccine 3rd dose, respectively). Before-after representation of IFN-γ production after Spike peptide stimulation in HD and allogenic HSCT recipients (1.C). Conclusion SARS-CoV-2 IGRA represents a useful tool to assess CMI, also in immunocompromised hosts. An additional 3rd BNT162b2 mRNA vaccine booster dose seems to enhance CMI in allogenic HSCT recipients. Further studies are needed to evaluate the duration of SARS-CoV-2 CMI in HSCT recipients compared to HD. Disclosures All Authors: No reported disclosures.

Background Several studies reported an increased rate of indeterminate QuantiFERON-TB Gold Plus (QFT-P) assay results in patients with severe Coronavirus Disease (COVID)-19. Methods Aim of the study was to longitudinally evaluate QFT-P responses in patients who survived COVID-19, with a previous indeterminate result. Results We observed 223 patients with an indeterminate QFT-P assay among 949 patients hospitalized because of COVID-19 (23,5%) during 2020 and 2021. 36 patients among those with an indeterminate QFT-P assay were enrolled for reassessing the test. In 12 patients peripheral blood lymphocyte subsets were also reassessed. Considering disease severity, 30 were classified as severe and 6 as non-severe. Median age was 57,5 (interquartile range [IQR]: 49,5-63,8), with a prevalence of male sex (M/F: 24/12); median Charlson Comorbidity Index was 2 (IQR: 1-3). The second QFT-P assay was performed after at least 1 month from the first assay (median time 7 months, IQR: 5-12 months). All QFT-P assays gave a determined result: 2 positive (5.5%) and 34 negatives (94,4%). A statistically significant difference was observed after comparing the laboratory parameters at the time of the first and the second QFT-P assay: the absolute counts of total lymphocyte, total CD3+, CD4+ and CD8+ T-lymphocytes were significantly increased (p< 0.001) while neutrophil absolute counts, neutrophil to lymphocyte (N/L) ratio, D-dimer, fibrinogen, ferritin, C-reactive protein (CRP) were significantly reduced (p< 0.0001). Concerning the QFT-P assay, interferon gamma (INF-γ) production in the Mitogen-Nil, TB1-Nil and TB2-Nil conditions were significantly increased (p< 0.0001; p=0.0019; p=0.0205, respectively) (Table 1 and Figure 1). Conclusion Once the acute phase of COVID-19 is resolved, inflammatory markers and peripheral blood leucocyte counts tend to normalize with an effective INF-γ production after specific and nonspecific stimulation. All the 36 QFT-P showed a determinate result. Moreover, we observed 2 positive QFT-P assay, supporting the importance of retesting patients with indeterminate result to identify latent tuberculosis infection and monitor patients for possible reactivation because of the immune-suppression associated with COVID-19. Disclosures All Authors: No reported disclosures.

Background To cope with the SARS-CoV-2 pandemic, several treatments were studied and out of these, monoclonal antibodies (MAbs) have shown efficacy to prevent the development of pneumonia after the infection Methods We conducted a retrospective, single-center study including patients with SARS-CoV-2 infection, treated with MAbs (bamlanivimab/etesevimab (B/E), casirivimab/imdevimab (C/I) or sotrovimab (S)) from March 2021 to February 2022 Results We included 504 patients with a median age of 62 years (IQR 49-72), 51% were males and 66% had completed the vaccination schedule according to the current Italian regulations. The most frequent eligibility criteria are summarized in figure 1. As for MAbs combination, patients were treated with B/E (54%), followed by C/I (30%) and S (16%). Outcomes are shown in Table 1. Nasopharyngeal swab (NPS) negativization time had a positive correlation with patients’ age (r=0.16; p=0.001), C-reactive protein (CRP) (r=0.26; p< 0.001) and creatinine values (r=0.22; p< 0.001) assessed at baseline (infusion day). Time to NPS negativization was 6.9 (95% C.I. [4.5-9.2]) days shorter for vaccinated compared to unvaccinated patients (p< 0.001). Patients treated with C/I had a negative NPS on average 4.5 (95% C.I.= [1.8-7.3] days earlier than patients treated with B/E; patients who received S reached negativization 6.0 (95% C.I.= [2.2, 9.9]) days earlier than those treated with B/E (p=0.004). Patients with positive outcome had a negative NPS on average 14.3 (95% C.I.= [6.8, 23.1)], 25.5 (95% C.I.= [18.9, 33.4] and 68.3 (95% C.I.= [47.7, 90.2]) days earlier than patients who needed hospitalization and patients who died (p< 0.001, p< 0.001, respectively). Unvaccinated patients had a higher rate of oxygen support need compared to vaccinated ones (p=0.006). Patients with worse outcomes were significantly older and had higher values of CRP and creatinine at baseline (p=0.04, p< 0.001, p< 0.001, respectively) Percentage of eligibility criteria of our patients The majority of patients had more than one criterion Clinical outcome of our patients Nasopharyngeal swab was repeated weekly, until negative Conclusion MAbs reduce the risk of hospitalization in fragile patients. Vaccinated patients had shorter time of NPS negativization and lower probability of hospitalization. Older age, higher CRP and creatinine values assessed at baseline, correlated with worse outcomes. S was the most effective treatment amongst MAbs used in our study Disclosures All Authors: No reported disclosures.