Performance of CURB-65 and ISARIC 4C mortality scores for hospitalized patients with confirmed COVID-19 infection in Saudi Arabia.

Background: The COVID-19 pandemic continues with new waves that could persist with the arrival of new SARS-CoV-2 variants. Therefore, the availability of validated and effective triage tools is the cornerstone for proper clinical management. Thus, this study aimed to assess the validity of the ISARIC-4C score as a triage tool for hospitalized COVID-19 patients in Saudi Arabia and to compare its performance with the CURB-65 score. Material and methods: This retrospective observational cohort study was conducted between March 2020 and May 2021 at KFHU, Saudi Arabia, using 542 confirmed COVID-19 patient data on the variables relevant to the application of the ISARIC-4C mortality score and the CURB-65 score. Chi-square and t-tests were employed to study the significance of the CURB-65 score and the ISARIC-4C score variables considering the ICU requirements and the mortality of COVID-19 hospitalized patients. In addition, logistic regression was used to predict the variables related to COVID-19 mortality. In addition, the diagnostic accuracy of both scores was validated by calculating sensitivities, specificities, positive predictive value, negative predictive value, and Youden's J indices (YJI). Results: ROC analysis showed an AUC value of 0.834 [95% CI; 0.800-0.865]) for the CURB-65 score and 0.809 [95% CI; 0.773-0.841]) for the ISARIC-4C score. The sensitivity for CURB-65 and ISARIC-4C is 75% and 85.71%, respectively, while the specificity was 82.31% and 62.66%, respectively. The difference between AUCs was 0.025 (95% [CI; -0.0203-0.0704], p = 0.2795). Conclusion: Study results support external validation of the ISARIC-4C score in predicting the mortality risk of hospitalized COVID-19 patients in Saudi Arabia. In addition, the CURB-65 and ISARIC-4C scores showed comparable performance with good consistent discrimination and are suitable for clinical utility as triage tools for hospitalized COVID-19 patients.

Effect of zinc supplementation on symptom reduction and length of hospital stay among pediatric patients with Coronavirus Disease 2019 (COVID-19)

Objectives Zinc is considered an essential multipurpose trace element because of its ability to act as a cofactor and signaling molecule. As reported in earlier studies of pediatric respiratory infection management, zinc exhibits potent immunoregulatory and antiviral properties, but its effects on pediatric patients with COVID-19 remain unknown. The aim of this study was to determine the extent to which zinc supplementation improves COVID-19 symptoms, length of hospitalization and, to determine how zinc supplementation impacts ICU admission, in-hospital mortality, need for ventilation, duration of ventilation, need for vasopressors, development of liver injury, or respiratory failure Methods Pediatric patients younger than 18 years with confirmed COVID-19 infection during the study period (March 1, 2020, to December 31, 2021) were recruited for this retrospective cohort study. The study population was divided into two arms (zinc/no zinc supplementation as an adjunct to standard therapy). Results Of 169 hospitalized patients who were screened, 101 met the inclusion criteria. No statistically significant association was found between the administration of zinc as adjunctive therapy and symptom reduction, intensive care unit (ICU) admission, or mortality (p = 0.105;p = 0.941, and p = 0.073, respectively). However, zinc supplementation was associated with a statistically significant reduction in respiratory failure and length of hospitalization (p = 0.004 and p = 0.017, respectively), also, zinc administration was associated with elevated serum creatinine (p= 0.01*) Conclusions Among pediatric patients with COVID-19, zinc supplementation was associated with shorter hospital stay. However, there was no significant difference between the two groups in terms of symptom improvement, in-hospital mortality, or ICU admission. In addition, the study raises question about the possibility of kidney injury as indicated by high levels of serum creatinine.

Effect of zinc supplementation on symptom reduction and length of hospital stay among pediatric patients with Coronavirus disease 2019 (COVID-19).

Objectives: Zinc is considered an essential multipurpose trace element because of its ability to act as a cofactor and signaling molecule. As reported in earlier studies of pediatric respiratory infection management, zinc exhibits potent immunoregulatory and antiviral properties, but its effects on pediatric patients with COVID-19 remain unknown. The aim of this study was to determine the extent to which zinc supplementation improves COVID-19 symptoms, length of hospitalization and, to determine how zinc supplementation impacts ICU admission, in-hospital mortality, need for ventilation, duration of ventilation, need for vasopressors, development of liver injury, or respiratory failure. Methods: Pediatric patients younger than 18 years with confirmed COVID-19 infection during the study period (March 1, 2020, to December 31, 2021) were recruited for this retrospective cohort study. The study population was divided into two arms (zinc/no zinc supplementation as an adjunct to standard therapy). Results: Of 169 hospitalized patients who were screened, 101 met the inclusion criteria. No statistically significant association was found between the administration of zinc as adjunctive therapy and symptom reduction, intensive care unit (ICU) admission, or mortality (p = 0.105; p = 0.941, and p = 0.073, respectively). However, zinc supplementation was associated with a statistically significant reduction in respiratory failure and length of hospitalization (p = 0.004 and p = 0.017, respectively), also, zinc administration was associated with elevated serum creatinine (p = 0.01*). Conclusions: Among pediatric patients with COVID-19, zinc supplementation was associated with shorter hospital stay. However, there was no significant difference between the two groups in terms of symptom improvement, in-hospital mortality, or ICU admission. In addition, the study raises question about the possibility of kidney injury as indicated by high levels of serum creatinine.

Variants of SARS-CoV-2: Influences on the Vaccines' Effectiveness and Possible Strategies to Overcome Their Consequences.

The immune response elicited by the current COVID-19 vaccinations declines with time, especially among the immunocompromised population. Furthermore, the emergence of novel SARS-CoV-2 variants, particularly the Omicron variant, has raised serious concerns about the efficacy of currently available vaccines in protecting the most vulnerable people. Several studies have reported that vaccinated people get breakthrough infections amid COVID-19 cases. So far, five variants of concern (VOCs) have been reported, resulting in successive waves of infection. These variants have shown a variable amount of resistance towards the neutralising antibodies (nAbs) elicited either through natural infection or the vaccination. The spike (S) protein, membrane (M) protein, and envelope (E) protein on the viral surface envelope and the N-nucleocapsid protein in the core of the ribonucleoprotein are the major structural vaccine target proteins against COVID-19. Among these targets, S Protein has been extensively exploited to generate effective vaccines against COVID-19. Hence, amid the emergence of novel variants of SARS-CoV-2, we have discussed their impact on currently available vaccines. We have also discussed the potential roles of S Protein in the development of novel vaccination approaches to contain the negative consequences of the variants' emergence and acquisition of mutations in the S Protein of SARS-CoV-2. Moreover, the implications of SARS-CoV-2's structural proteins were also discussed in terms of their variable potential to elicit an effective amount of immune response.

Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID.

The COVID-19 pandemic has caused havoc all around the world. The causative agent of COVID-19 is the novel form of the coronavirus (CoV) named SARS-CoV-2, which results in immune system disruption, increased inflammation, and acute respiratory distress syndrome (ARDS). T cells have been important components of the immune system, which decide the fate of the COVID-19 disease. Recent studies have reported an important subset of T cells known as regulatory T cells (Tregs), which possess immunosuppressive and immunoregulatory properties and play a crucial role in the prognosis of COVID-19 disease. Recent studies have shown that COVID-19 patients have considerably fewer Tregs than the general population. Such a decrement may have an impact on COVID-19 patients in a number of ways, including diminishing the effect of inflammatory inhibition, creating an inequality in the Treg/Th17 percentage, and raising the chance of respiratory failure. Having fewer Tregs may enhance the likelihood of long COVID development in addition to contributing to the disease's poor prognosis. Additionally, tissue-resident Tregs provide tissue repair in addition to immunosuppressive and immunoregulatory activities, which may aid in the recovery of COVID-19 patients. The severity of the illness is also linked to abnormalities in the Tregs' phenotype, such as reduced expression of FoxP3 and other immunosuppressive cytokines, including IL-10 and TGF-beta. Hence, in this review, we summarize the immunosuppressive mechanisms and their possible roles in the prognosis of COVID-19 disease. Furthermore, the perturbations in Tregs have been associated with disease severity. The roles of Tregs are also explained in the long COVID. This review also discusses the potential therapeutic roles of Tregs in the management of patients with COVID-19.

Inflammatory and vascular biomarkers in post-COVID-19 syndrome: A systematic review and meta-analysis of over 20 biomarkers.

Severe acute respiratory syndrome coronavirus 2 may inflict a post-viral condition known as post-COVID-19 syndrome (PCS) or long-COVID. Studies measuring levels of inflammatory and vascular biomarkers in blood, serum, or plasma of COVID-19 survivors with PCS versus non-PCS controls have produced mixed findings. Our review sought to meta-analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty-four biomarkers from 23 studies were meta-analysed. Higher levels of C-reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02-0.39), D-dimer (SMD = 0.27; 95% CI: 0.09-0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05-0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02-0.66) were found in COVID-19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12-0.48) and interleukin-6 (SMD = 0.30; 95% CI: 0.12-0.49) were also significantly higher in PCS than non-PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS.

Incidence and risk factors of adverse drug reactions in patients with coronavirus disease 2019: A pharmacovigilance experience utilizing an ADR trigger tool.

BACKGROUND: Since the World Health Organization declared coronavirus disease (COVID-19) as a pandemic, most countries started treating their patients with various therapies. However, the data regarding their safety and effectiveness is still lacking. OBJECTIVES: We aimed to evaluate the adverse drug reactions (ADRs) incidence and their predisposing factors among COVID-19 patients. METHODS: A retrospective observational study that was conducted at a tertiary academic hospital from March - June 2020. Patients were included if they were ≥ 18 years old, inpatient, had a reverse transcriptase-polymerase chain reaction (PCR) positive for COVID-19, and were treated with; (lopinavir-ritonavir, hydroxychloroquine, chloroquine, favipiravir, ribavirin, or interferon-ß) either as monotherapy or combination therapy for three days or longer. The data of eligible patients were retrieved from the electronic medical records. A standardized data collection form was designed to collect patient demographics, COVID-19 severity based on the Saudi Ministry of Health management protocols, antiviral therapies, duration of therapy, and length of stay (LOS). The ADRs were identified via conducting a comprehensive review using predefined triggers and were evaluated using Naranjo Score. RESULTS: A total of 155 patients were included of which 123 (79.4%) were males. In our sample, the incidence proportion of ADRs per patient was 72.3%. A total of 287 ADRs were identified most of them were hepatic (n = 101, 35.2%), gastrointestinal (n = 59, 20.6%), hematological (n = 47, 16%), and endocrine (n = 45, 15%). Hydroxychloroquine was the most common drug associated with ADRs (n = 155). The length of stay (10 - 20 days) was the only statistically significant with the ADR incidence (p-value = 0.008; 95 %CI 1.216:3.568). CONCLUSIONS: The ADRs are prevalent among COVID-19 patients, which assure the importance of implementing active hospital-based pharmacovigilance systems.