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.

sCXCL16 as a prognostic biomarker for COVID-19 outcome.

As elevated levels of the soluble CXCL16 (sCXCL16) chemokine have been reported in severe coronavirus disease 2019 (COVID-19) patients, this study examined whether sCXCL16 concentration on the first day of hospitalization predicted death in COVID-19 patients. A total of 76 patients with COVID-19 were admitted to the Military Hospital of Tunis, Tunisia, between October 2020 and April 2021, and later classified as survivors or nonsurvivors based on their outcomes. At admission, the groups were matched by age, gender, comorbidities, and the percentage of patients with moderate conditions. On the first day of admission, serum's sCXCL16 concentrations were measured using a magnetic-bead assay. There was an eightfold increase in serum sCXCL16 levels in the nonsurvivors' group (3661.51 ± 2464.87 pg/mL vs. 454.3 ± 338.07 pg/mL, p < 0.0001). For the optimal cutoff value of sCXCL16 at 2095 pg/mL, we found a 94.6% sensitivity and a 97.4% specificity, with an area under curve of 0.981 (p = 5.03E-08; 95% confidence interval [95% CI]: 0.951-1.0114). Considering the risk of death at a concentration above the threshold, the unadjusted odds ratio was 36 (p < 0.0001). The adjusted odd ratio was estimated at 1.003 (p < 0.0001; 95% CI: 1.002-1.004). Finally, there was a significant difference between survival and nonsurvival groups in leukocyte numbers (p = 0.006), lymphocytes (p = 0.001), polymorphonuclear neutrophils (p = 0.001), and C-reactive protein levels (p = 0.007), except for monocytes (p = 0.881). Based on these results, sCXCL16 level could be used for detecting nonsurvival COVID-19 patients. Therefore, we recommend assessing this marker in hospitalized COVID-19 patients.

[Comparative study of patients hospitalized for SARS-CoV-2 infection in two consecutive waves in Tunisia]. / Étude comparative de patients hospitalisés pour une infection SARS-CoV-2 au cours de deux vagues consécutives en Tunisie.

Introduction: Since December 2019, a novel coronavirus (SARS-CoV-2) has triggered a global pandemic with a heavy medical and societal-economic toll. The health consequences were not similar during the successive waves that affected several countries. The aim of our study was to compare the sociodemographic, clinical and evolutionary features of COVID-19 patients hospitalized at the Military Hospital of Tunis (HMPIT) during the 2nd and 3rd waves that affected the country. Patients and methods: Observational prospective study involving 1,527 COVID-19 patients hospitalized at HMPIT over 11 months, divided into two periods: from July 2020 to December 2020 called the second wave (V2) and from January 2021 to May 2021 called the third wave (V3). We compared the epidemiological data, the clinical form and the evolution of the patients for each period. Results: The number of hospitalized patients was 636 during V2 compared to 891 during V3. Average age was 63.5 ± 15.3 years during V2 versus 65.8 ± 17.8 years during V3 (P = not significant [NS]). The percentage of young adults [18-40 years] was 6.5% during V2 compared to 6.7% during V3 (P = NS). The gender ratio (M/F) was 1.59 for V2 and 1.42 for V3 (P = NS). Comorbidities were present in 65% of V2 patients and 66.3% of V3 patients (P = NS), with hypertension being the most prevalent one in both groups (47.2% for V2 versus 44.9% for V3; P = NS), followed by overweight, dyslipidemia and diabetes (33% for V2 versus 39.3% for V3; P = 0.012). The median duration between symptoms onset and hospitalization was 7 days [5-10] during V2 versus 8.5 days during V3 [5-12] (P = 0.0004). The severe clinical form was present in 49% of patients admitted during V2 compared to 34.8% during V3 (P < 10-3). The critical form represented 18.6% of cases during V2 against 16.8% during V3 (P = NS). The average hospital length of stay in COVID units (outside of intensive care unit) was 8.4 ± 5.4 days during V2 and 9.8 ± 5.7 days during V3. The average length of stay was significantly longer for the intensive care unit (11.3 ± 3.4 days for V2 versus 13.8 ± 3.9 days for V3; P = 0.01). The case fatality rate was 24.5% during V2 and 20.7% during V3 (P = NS). Median age of death was 70.2 years [42-88] during V2 and 70.4 years [22-96] during V3 with 2 patients less than 40 years of age (1%) for the latter period. The gender ratio (M/F) of deceased patients was 3.21 for V2 and 1.5 for V3 (P = 0.001). The case fatality rate was higher in the intensive care unit (65.4% for V2 versus 69.7% for V3; P = NS). Causes of death were dominated by ARDS (acute respiratory distress syndrome) for both periods (55.1% for V2 versus 70.8% for V3; P = 0.002), followed by septic shock (12.8% for V2 versus 10.8% for V3; P = NS) and multi-organ failure (9.6% for V2 versus 7.0% for V3; P = NS). Conclusion: This study revealed a decrease in severe and critical clinical forms during the 3rd wave, as well as a decrease in the case fatality rate compared to the previous wave, due to improved management and vaccination. On the other hand, the percentage of ARDS was significantly higher during this wave probably related to the beginning of circulation in our country of the Delta variant causing more severe clinical cases.

Étude comparative de patients hospitalisés pour une infection SARS-CoV-2 au cours de deux vagues consécutives en Tunisie Comparative study of patients hospitalized for SARS-CoV-2 infection in two consecutive waves in Tunisia

Résumé Introduction Le nouveau coronavirus (SARS-CoV-2) a déclenché une pandémie mondiale avec des conséquences sanitaires qui n’étaient pas similaires lors des vagues successives qui ont touché plusieurs pays. Le but de notre étude était de comparer les caractéristiques socio-démographiques, cliniques et évolutives des patients atteints de la COVID-19 hospitalisés au cours des 2e et 3e vagues survenues en Tunisie. Patients et méthodes Étude prospective observationnelle incluant 1 527 patients atteints de la COVID-19 et hospitalisés à l'Hôpital militaire de Tunis, s’étalant sur 11 mois, répartie en deux périodes : de juillet 2020 jusqu'en décembre 2020 appelée la deuxième vague (V2) et de janvier 2021 jusqu'en mai 2021 appelée la troisième vague (V3). Résultats 636 patients ont été hospitalisés au cours de V2 contre 891 au cours de V3. L’âge moyen était de 63,5 ± 15,3 ans au cours de V2 contre 65,8 ± 17,8 ans au cours de V3 (P = non significatif [NS]). Le sexe-ratio (H/F) était de 1,59 pour V2 et de 1,42 pour V3 (P = NS). La forme clinique sévère représentait 49% des cas pendant V2 contre 34,8% pendant V3 (P < 10-3). La forme critique représentait 18,6% des cas au cours de V2 contre 16,8% au cours de V3 (P = NS). Le taux de létalité était de 24,5% au cours de V2 et de 20,7% au cours de V3 (P = NS). L’âge médian des patients décédés était de 70,2 ans [42-88 ans] au cours de V2 et de 70,4 ans [22-96 ans] au cours de V3. Le sexe-ratio (H/F) des patients décédés était de 3,21 pour V2 et de 1,5 pour V3 (P = 0,001). Le taux de létalité était plus élevé dans le service de réanimation (65,4% pour V2 versus 69,7% pour V3;P = NS). Les causes de décès étaient dominées par le SDRA (syndrome de détresse respiratoire aiguë) pour les deux périodes (55,1% pour V2 versus 70,8% pour V3;P = 0,002), suivi de l’état de choc septique (12,8% pour V2 versus 10,8% pour V3;P = NS) et de la défaillance multiviscérale (9,6% pour V2 versus 7,0% pour V3;P = NS). Conclusion Nous avons observé une diminution des formes cliniques sévères et critiques au cours de V3, ainsi qu'une baisse du taux de létalité par rapport à V2 grâce à l'amélioration de la prise en charge ainsi qu’à la vaccination. En revanche, le pourcentage de SDRA était significativement plus élevé au cours de V3 probablement en rapport avec le début de circulation dans notre pays de la souche Delta à l'origine de tableaux cliniques plus sévères.

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.

COVID-19 prophylaxis with doxycycline and zinc in health care workers: a prospective, randomized, double-blind clinical trial.

OBJECTIVES: This study aims to assess the efficacy of a combination treatment of doxycycline and zinc in the primary prevention of COVID-19 infection in Tunisian health care workers compared with two control groups. METHODS: We conducted a prospective, randomized, double-blind clinical trial over 5 months to determine the efficacy of a preventive combination treatment dose of doxycycline (100 mg/day) and zinc (15 mg/day), compared with a single-dose treatment with doxycycline versus placebo. The effectiveness of preventive treatment was measured by the significant decline in the number of cases of COVID-19 infection and/or a decrease in the viral load as determined by SARS-CoV-2 cycle threshold value using reverse transcription polymerase chain reaction tests. RESULTS: We detected a significant decrease of SARS-CoV-2 infection in the group that received both doxycycline and zinc compared with other participants. We also demonstrated that COVID-19 infection was neither associated with diabetes (P = 0.51) nor associated with hypertension (P = 0.99), asthma (P = 0.52), and chronic obstructive pulmonary disease (P = 0.27). CONCLUSION: Our findings indicated that preventive therapy reduced the risk of SARS-CoV-2. These results suggest that the combination of doxycycline and zinc has a protective effect in patients with SARS-CoV-2 infection.

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.

Acceptability of COVID-19 vaccine: a cross-sectional study in a Tunisian general hospital.

INTRODUCTION: the year 2020 was marked by the COVID-19 pandemic that killed more than one million people. Several vaccines have been developed and vaccination campaigns started in December 2020. The objective of our study was to assess the acceptability of the COVID-19 vaccine by hospital staff. METHODS: cross-sectional study conducted on a representative sample drawn at random from the staff of the Military General Hospital of Tunis. Data was collected between August and September 2020 by a clinical psychologist. We studied the associations between the different characteristics of our population and the decision to accept or refuse vaccination against COVID-19. RESULTS: a total of 398 hospital staff agreed to answer our questionnaire. Our sample was composed of 9% (n=36) physicians, 0.9% (n=3) pharmacists, 41.3% (n=164) paramedics, 16.1% (n=64) cleaning staff and 32.7% (n=131) administrative staff. The rapid discovery of the vaccine was hoped by 97% (n=386). Vaccination was considered a means of collective protection by 84.7% (n=337). However, only 58% (n=231) agreed to be vaccinated by the COVID-19 vaccine. The main factors significantly associated with acceptance of the COVID-19 vaccine was previous influenza vaccination (aOR: 2.58, 95% CI 1.69-3.94; p=0.000). CONCLUSION: apprehension about vaccination does not appear to be sparing the future COVID-19 vaccine. Fear of vaccine side effects outweighs fear of the disease, even among hospital staff. To achieve vaccination coverage, several awareness and communication activities must be carried out.

Immediate Psychological Responses, Stress Factors, and Coping Behaviors in Military Health-Care Professionals During the COVID-19 Pandemic in Tunisia.

Objective: The COVID-19 epidemic began in Tunisia in March 2020; health-care workers (HCWs) were suddenly confronted with a particularly stressful situation. The aim of this study was to assess the psychological responses of HCWs during the epidemic, determine the stressors and identify ways to cope. Methods: This cross-sectional study used an online questionnaire that included 62 questions. ANOVAs and t-tests were used to compare the responses between professional groups, age groups, and genders. Results: Questionnaires were completed by 368 HCWs. HCWs believed they had a social and professional obligation to continue working long hours (95.3%). They were anxious regarding their safety (93.7%) and the safety of their families (97.8%). Youthful age (p = 0.044) and female gender (ps <0.046) were identified as stressors. The availability of personal protective equipment (PPE; 99.7%) and good communication between colleagues (98.1%) and managers (91.6%) were important protective factors. Family and friend support (95.9%), following strict protective measures (99.4%), knowing more about COVID-19 (94.8%), adopting a positive attitude (89.6%), and engaging in leisure activities (96.1%) helped in dealing with this epidemic. Conclusion: This study highlights the importance of providing HCWs with infection control guidelines and adequate PPE. Communication and support within the team and maintaining family support help in coping with this stressful situation.