Humoral and cellular response of two different vaccines against SARS-CoV-2 in a group of healthcare workers: An observational study.

On March 13, 2021, Tunisia started a widespread immunization program against SARS-CoV-2 utilizing different vaccinations that had been given emergency approval. Herein, we followed prospectively a cohort of participant who received COVID-19 vaccine (Pfizer BioNTech and Sputnik-Gameleya V). The goal of this follow-up was to define the humoral and cellular immunological profile after immunization by assessing neutralizing antibodies and IFN- γ release. 26 vaccinated health care workers by Pfizer BioNTech (n=12) and Sputnik-Gameleya V (n=14) were enrolled from June to December 2021 in Military hospital of Tunis. All consenting participants were sampled for peripheral blood after three weeks of vaccination. The humoral response was investigated by the titer of anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies to S1 protein. The CD4 and CD8 T cell responses were evaluated by the QuantiFERON® SARS-CoV-2 (Qiagen® Basel, Switzerland). Regardless the type of vaccine, the assessment of humoral and cellular response following vaccination showed a strong involvement of the later with expression of IFN-γ as compared to antibodies secretion. Moreover, we showed that people with past SARS-CoV-2 infection developed high levels of antibodies than those who are not previously infected. However, no significant difference was detected concerning interferon gamma (IFN-γ) expression by CD4 and CD8 T cells in health care worker (HCW) previously infection or not with COVID-19 infection. Analysis of immune response according to the type of vaccine, we found that Pfizer BioNTech induced high level of humoral response (91.66%) followed by Sputnik-Gameleya V (64.28%). However, adenovirus vaccine gave a better cellular response (57.14%) than mRNA vaccine (41.66%). Regarding the immune response following vaccine doses, we revealed a significant increase of neutralizing antibodies and IFN-γ release by T cells in patients fully vaccinated as compared to those who have received just one vaccine. Collectively, our data revealed a similar immune response between Pfizer BioNTech and Sputnik-Gameleya V vaccine with a slight increase of humoral response by mRNA vaccine and cellular response by adenovirus vaccine. It's evident that past SARS-CoV-2 infection was a factor that contributed to the vaccination's increased immunogenicity. However, the administration of full doses of vaccines (Pfizer BioNTech or Sputnik-Gameleya V) induces better humoral and cellular responses detectable even more than three months following vaccination.

Immune Cell Response during COVID-19 Infection and following SARS-CoV-2 Vaccination in Patients Admitted to Intensive Care Unit.

Background: Immune response plays a crucial role in virus clearance during COVID-19 infection and underpins vaccine efficacy. Herein, we aimed to assess the immune response during COVID-19 infection and following SARS-CoV-2 vaccination. Methods: In this retrospective study, 94 confirmed COVID-19 patients admitted to the intensive care unit were categorized into unvaccinated patients (n = 50), including 33 deceased and 17 discharged patients, and vaccinated group (n = 44) with 26 deceased and 18 discharged patients. Records of patients with severe COVID-19 admitted to the ICU between March, 2021 and March, 2022 were gathered and analyzed. Result: The assessment of immune cell counts revealed a large rise of neutrophils associated to decrease number of lymphocytes in patients with COVID-19 infection. In dead patients, we detected a significant correlation between neutrophils and inflammatory parameters such as IL-6 and CRP. Moreover, analysis of immune cell count following vaccination did not reveal any significant difference. However, the most substantial result, herein, detected is the decrease level of IL-6 in vaccinated patients as compared to unvaccinated. The reduce level of IL-6 following vaccination is observed in discharged patients as compared to deceased. Regarding the level of mortality after vaccination, we showed that all patients who received the first dose were died (46.1%, n = 12) as compared to those who have received two doses (34.6%, n = 9) and the third dose of vaccine (19.23%, n = 3) (p=0.0018). Strikingly, studying the inflammatory parameters after each vaccine dose, we revealed a significant decrease of IL-6 level after the booster dose (third dose), especially in vaccinated discharged patients. Conclusions: Neutrophils combined with IL-6 and CRP can be very useful markers to predict disease severity in patients admitted to ICU. The decrease level of IL-6 in vaccinated group pointed out the impact of vaccination to prevent inflammatory cytokine release.

Deciphering the balance of IL-6/IL-10 cytokines in severe to critical COVID-19 patients.

The severity of COVID-19 is largely determined by the inflammatory response, a "Cytokine storm," that involves both pro- and anti-inflammatory cytokines. In the current study we investigated the balance of pro- and anti-inflammatory status as represented by the levels of IL-6/IL-10 in severe to critical COVID-19 patients. 66 confirmed COVID-19 patients admitted to the ICU were categorized into groups according to the mortality and respiratory failure. Data were collected retrospectively in ICU, including a peripheral immune cells and infection-related biomarker CRP. The measurements of cytokine levels were performed by Immulite analyzer for IL-6 and ELISA sandwich for IL-10. In addition, longitudinal measurement of IL-6 was performed during 5 days post admission. Longitudinal assays showed that IL-6 was sustained at a medium level within 5 days post admission in severe cases who survived or not requiring mechanical ventilation, whereas it was sustained at high levels throughout the disease course in either deceased cases or who developed respiratory failure. The ratio of IL-6/lymphocytes was positively correlated with the risk of mortality, while IL-10/lymphocytes ratio could predict respiratory failure in ICU. IL-6/IL-10 profiling revealed that deceased patients have different magnitudes of both IL-6 and IL-10 cytokine release. Notably, excessive levels of IL-6 concomitant with high levels of IL-10 were more common in diseased COVID-19 patients. Taking into account the IL-6/IL-10 profiling may help clinicians to identify the right time of anti-inflammation treatment and select patients who will respond to anti-cytokine therapies and maintain an adequate inflammatory response for SARS-CoV-2 clearance.

The outcome of laparoscopic pancreatoduodenectomy is improved with patient selection and the learning curve.

BACKGROUND: In our first experience, laparoscopic pancreatoduodenectomy (LPD) was associated with higher morbidity than open PD. Since, the surgical technique has been improved and LPD was avoided in some patients at very high risk of postoperative pancreatic fistula (POPF). We provide our most recent results. METHOD: Between 2011 and 2018, 130 LPD were performed and divided into 3 consecutive periods based on CUSUM analysis and compared: first period (n = 43), second period (n = 43), and third period (n = 44). RESULTS: In the third period of this study, LPD was more frequently performed in women (46%, 39%, 59%, p = 0.21) on dilated Wirsung duct > 3 mm (40%, 44%, 57%; p = 0.54). Intraductal papillary mucinous neoplasm (IPMN) became the primary indication (12%, 39%, 34%; p = 0.037) compared to pancreatic adenocarcinoma (35%, 16%, 16%; p = 0.004). Malignant ampulloma re-increased during the third period (30%, 9%, 20%; p = 0.052) with the amelioration of surgical technique. The operative time increased during the second period and decreased during the third period (330, 345, 270; p < 0.001) with less blood loss (300, 200, 125; p < 0.001). All complications decreased, including POPF grades B/C (44%, 28%, 20%; p = 0.017), bleeding (28%, 21%, 14%; p = 0.26), Clavien-Dindo III-IV (40%, 33%, 16%; p = 0.013), re-interventions (19%, 14%, 9%; p = 0.43), and the hospital stay (26, 19, 18; p = 0.045). Less patients with similar-sized adenocarcinoma were operated during the second period (70%, 33%, 59%; p = 0.002) with more harvested lymph nodes in the third period (21,19, 25; p = 0.031) and higher R0 resection (70%, 79%, 84%; p = 0.5). On multivariate analysis the protective factors against POPF of grades B/C were pancreatic adenocarcinoma and invasive IPMN, BMI < 22.5 kg/m2, and patients operated in the third period. CONCLUSION: This study showed that the outcome of LPD significantly improves with the learning curve and patient selection. For safe implementation and during the early learning period, LPD should be indicated in patients at lower risk of POPF.

Outcomes of treatment of severe COVID-19 pneumonia with tocilizumab: a report of two cases from Tunisia.

The SARS CoV-2 pandemic is a global health threat with high morbidity and mortality (1 to 4%) rates. COVID-19 is correlated with important immune disorders, including a "cytokine storm". A new therapeutic approach using the immunomodulatory drug, Anti-IL6 (tocilizimub), has been proposed to regulate it. We report here the first Tunisian experience using tocilizimub in two severe cases of COVID-19 pneumonia. The diagnosis was confirmed by chest scan tomography. Biological parameters showed a high level of Interleukin-6 (IL-6) that increased significantly during hospitalization. The patients developed hypoxia, so they received intravenously 8 mg/kg body weight tocilizumab. There was a resultant decrease in the level of IL6, with clinically good evolution. Blocking the cytokine IL-6 axis is a promising therapy for patients developing COVID-19 pathology.

Pancreatic fistula following laparoscopic distal pancreatectomy is probably unrelated to the stapler size but to the drainage modality and significantly decreased with a small suction drain.

INTRODUCTION: Risk factors of postoperative pancreatic fistula (POPF) after laparoscopic distal pancreatectomy (LDP) are not well known and were studied, including the stapler cartridge size and drainage modality. METHODS: Between January 2008 and December 2016, 181 LDP were performed and the pancreas was sectioned by stapler in 130 patients (72%). Patients received white (2.5 mm), blue (3.5 mm), or green (4.1 mm) staplers and the size was not based on any pre or peroperative randomization. As primary analysis of the first 84 patients (28 in each group) showed no effect of stapler size on POPF, we decided to use the white (total = 47) or blue and finally the blue (total = 55) of medium size for standardization. Drainage was obtained by multi-tubular drain (first, 79) and a small suction drain (last, 102). Risk factors of POPF were studied and grades B and C were compared to grade A or no POPF. RESULTS: POPF (n = 66; 36%) was of grade A (n = 25, 14%), grade B (n = 32, 18%), and grade C (n = 9, 5%). The comparison of the three groups of staplers showed that the blue stapler was used more with a small suction drain (85 vs 23%, p < 0.0001), had lower rate of grade B POPF (p = 0.028), and a shorter hospital stay (p = 0.004). On multivariate analysis, only the use of a small suction drain was associated with significant decrease in grades B and C POPF (6 vs 44%, odds ratio 7.385 (1.919-28.418); p = 0.004). CONCLUSION: The occurrence of POPF following LDP is influenced by the type of drainage alone and is significantly decreased with a small suction drain.

Effect of Ondansetron on the Occurrence of Hypotension and on Neonatal Parameters during Spinal Anesthesia for Elective Caesarean Section: A Prospective, Randomized, Controlled, Double-Blind Study.

To prevent hypotension during spinal anesthesia for caesarean section, we assessed IV ondansetron of invasive maternal hemodynamic and fetal gazometric parameters.

Lower incidence of hypotension following spinal anesthesia with 6% hydroxyethyl starch preload compared to 9 ‰ saline solution in caesarean delivery.

BACKGROUND: Hypotension is a common complication following spinal anesthesia for cesarean delivery. Techniques to prevent hypotension include preloading intravenous fluid. AIM: To compare the effect of two preloading regimens: 6% hydroxyethyl starch (HES) and 9‰ saline solution, to prevent hypotension after spinal anesthesia in cesarean delivery. METHODS: 105 patients undergoing intrathecal anesthesia for elective cesarean delivery were randomized and allocated to receive a preload of 500 ml HES 130/0.4 (HES Group) or a preload of 1500 ml 9‰ saline solution (CR group). Blood pressure and heart rate were recorded at baseline and after spinal anesthesia (every minute for the first 10 min, every 3 min for the next 10 min, and then every 5 min for the last 20 min). The primary outcome was to compare the incidence of hypotension (defined as a 20% reduction in systolic arterial pressure from baseline) between the two preloading regimens. Vasopressor requirements (i.v. bolus of 6 mg ephedrine) were also compared. RESULTS: The incidence of hypotension was 87% in the CR group and 69% in the HES group (p= 0.028). Ephedrine requirement, incidence of nausea, and/or vomiting and neonatal outcome did not significantly differ between the two groups. CONCLUSION: The incidence of hypotension was lower after preloading of 500 mL of HES 130/0.4 than preloading with 1500 mL of 9‰ saline solution.