Real-World Effectiveness of Four Types of COVID-19 Vaccines.

BACKGROUND: There is a scarcity of evidence regarding the real-world effectiveness of coronavirus disease 2019 (COVID-19) vaccines. This was the first study to evaluate the effectiveness of four types of vaccines against asymptomatic and symptomatic infection, and COVID-19 outcomes among the general population. METHODS: This was a matched comparison group quasi-experimental study conducted in Jordan between 1 January and 29 August 2021. In the first part of the study, 1200 fully vaccinated individuals were matched with 1200 unvaccinated control participants. In order to measure vaccine effectiveness, the infection rates of both vaccinated and unvaccinated groups were calculated. The second part of the study included measuring specific anti-SARS CoV-2 immune cells and antibodies. RESULTS: BNT162b2 (Pfizer, New York, NY, USA) showed a significantly higher effectiveness against asymptomatic COVID-19 infection (91.7%) and hospitalization (99.5%) than BBIBP-CorV (Sinopharm, Beijing, China) (88.4% and 98.7%, respectively) and ChAdOx1 nCoV-19 (AstraZeneca, Cambridge, UK) (84.3%, and 98.9%, respectively). The effectiveness rates of the Sputnik V (Gamaleya Research Institute, Moscow, Russia) vaccine against asymptomatic, symptomatic, and hospitalization were 100%, 100%, and 66.7%, respectively. The highest median anti-spike (S) IgG values were seen in individuals who received BNT162b2 (2.9 AU/mL) and ChAdOx1 nCoV-19 (2.8 AU/mL) vaccines. The levels of anti-S IgG were significantly decreased after 7 months of vaccination with BNT162b2 and BBIBP-CorV. There were significant decreases in the median number of neutralizing antibodies one month and seven months after receiving BNT162b2 (from 88.5 to 75.2 4 Bioequivalent Allergen Unit per milliliter/mL), BBIBP-CorV (from 69.5 to 51.5 BAU/mL), and ChAdOx1 nCoV-19 (from 69.2 to 58.BAU/mL) vaccines. The highest percentage of T cells specific to COVID-19 vaccine was found in individuals who received BNT162b2 (88.5%). CONCLUSION: All four vaccines evaluated in this study showed effectiveness against asymptomatic COVID-19 infection, symptomatic infection, hospitalization, and death. Furthermore, BNT162b2, BBIBP-CorV, and ChAdOx1 nCoV-19 induced high levels of immunology markers within one month of vaccination.

Safety, Tolerability, and Pharmacokinetics of Nebulized Hydroxychloroquine: A Pilot Study in Healthy Volunteers.

Background: Early in the coronavirus disease 2019 (COVID-19) pandemic, hydroxychloroquine (HCQ) drew substantial attention as a potential COVID-19 treatment based on its antiviral and immunomodulatory effects in vitro. However, HCQ showed a lack of efficacy in vivo, and different groups of researchers attributed this failure to the insufficient drug concentration in the lung following oral administration (HCQ is only available in the market in the tablet form). Delivering HCQ by inhalation represents a more efficient route of administration to increase HCQ exposure in the lungs while minimizing systemic toxicity. In this pilot study, the safety, tolerability, and pharmacokinetics of HCQ nebulizer solution were evaluated in healthy volunteers. Methods: Twelve healthy participants were included in this study and were administered 2 mL of HCQ01 solution (equivalent to 25 mg of HCQ sulfate) through Aerogen® Solo, a vibrating mesh nebulizer. Local tolerability and systemic safety were assessed by forced expiratory volume in the first and second electrocardiograms, clinical laboratory results (e.g., hematology, biochemistry, and urinalysis), vital signs, and physical examinations. Thirteen blood samples were collected to determine HCQ01 systemic exposure before and until 6 hours after inhalation. Results: The inhalation of HCQ01 was well tolerated in all participants. The mean value of Cmax for the 12 participants was 9.66 ng/mL. Tmax occurred at around 4.8 minutes after inhalation and rapidly decreased thereafter. The reported systemic exposure was very low with a mean value of 5.28 (0.6-15.6) ng·h/mL. Conclusion: The low systemic concentrations of HCQ01 of 9.66 ng/mL reported by our study compared with 1 µg/mL previously predicted after 200 mg BID oral administration, and the safety and tolerability of HCQ01 administered as a single dose through nebulization, support the assessment of its efficacy, safety, and tolerability in further studies for the treatment of COVID-19.

Active Safety Surveillance of Four Types of COVID-19 Vaccines: A National Study from Jordan.

BACKGROUND: Although the Pfizer-BioNTech (BNT162b2), Oxford-AstraZeneca (ChAdOx1 nCoV-19), Sinopharm (BBIBP-CorV), and Sputnik V coronavirus disease 2019 (COVID-19) vaccines have been granted emergency approval in many nations, their safety has never been studied and compared in one community-based study. This study aimed to investigate and compare the incidence, nature, severity, and predictors of adverse events following immunization (AEFIs) with COVID-19 vaccines. METHOD: This was a prospective observational study conducted in Jordan between 1 January and 21 September 2021. A team of pharmacists and nurses (n = 407) collected the local and systemic AEFIs of four COVID-19 vaccines by prospectively contacting participants registered in the national vaccination program platform. A red-flag technology was inserted to classify and track rare and serious AEFIs. RESULTS: This study included 658,428 participants who were vaccinated with 1,032,430 doses; 610,591, 279,606, 140,843, and 1390 participants received the first and second doses of the BNT162b2, BBIBP-CorV, ChAdOx1 nCoV-19, and Sputnik V vaccines, respectively. The overall incidence of AEFIs was 28.8%, and the overall rates of systemic, local, and immediate hypersensitivity AEFIs were 22.2%, 18.8%, and 0.5%, respectively. The highest proportions of immediate hypersensitivity AEFIs and systemic AEFIs were reported after administration of the Sputnik V vaccine and ChAdOx1 nCoV-19 first dose, respectively. The most severe AEFIs were reported after ChAdOx1 nCoV-19 first dose and BNT162b2 second dose. The hospitalization and mortality rates after vaccination were 20 in 10,000 and 1 in 10,000, respectively. Based on red-flag tracking, the top three outcome events were lymphadenopathy (157.9/100,000), anxiety disorders (136.6/100,000), and lower respiratory tract infection (100.9/100,000), with Guillain-Barré syndrome (1.8/100,000), vasculitis (3.0/100,000), and myopericarditis (4.8/100,000) being the least common. CONCLUSION: The incidence rates of local, systemic, and immediate hypersensitivity AEFIs of four COVID-19 vaccines occur frequently. High incidence rates of rare and serious AEFIs were reported in this study. Younger participants, females, those who had previously had COVID-19, and smokers were more likely to encounter AEFIs.

Mitigating psychological distress in healthcare workers as COVID-19 waves ensue: a repeated cross-sectional study from Jordan.

BACKGROUND: Jordan has experienced several COVID-19 waves in the past 2 years. Cross-sectional studies have been conducted to evaluate distress in healthcare practitioners (HCPs), but there is limited evidence with regards to the impact of continuing pandemic waves on levels of distress in HCPs. We previously studied psychological distress in HCPs during the start of the pandemic (period 1, when cases were infrequent and the country was in lockdown), and demonstrated that HCPs were experiencing considerable stress, despite the country reporting low caseloads at the time. In this study, we sought to utilize the same methodology to reexamine levels of distress as COVID-19 peaked in the country and HCPs began managing large numbers of COVID-19 cases (period 2). METHODS: A cross-sectional online survey utilizing a tool previously used during period 1 was completed by HCPs working in various settings. Demographic, professional and psychological factors such as distress, anxiety, depression, burnout, sleep issues, exhaustion, and fear were assessed; and coping strategies also were measured. Items in the tool were assessed for reliability and validity. A multivariable regression was used to identify factors that continued to impact distress during period 2. RESULTS: Samples in both periods (n = 937, n = 876, respectively) were relatively comparable in demographic characteristics, but in period 2, a greater proportion of nurses and healthcare practitioners reported working in general hospitals. During the pandemic peak (period 2), 49.0% of HCPs reported high levels of distress (compared to 32% in period 1); anxiety and depression scores were approximately 21% higher in period 2; and 50.6% reported fatigue (compared to 34.3% in period 1). Variables significantly associated with greater distress in period 2 included experiencing burnout, experiencing sleep disturbances, being fatigued, having fatalistic fears, and having fears related to workload. Conversely, being male, reporting satisfaction at work, and using positive coping practices were associated with a significantly lower odds of being in distress. CONCLUSIONS: Between the two periods (early pandemic and first wave), COVID-19-related mental health continued to deteriorate among HCPs, highlighting the need to do more to support HCP front-liners facing COVID-19 surges.

The inevitability of Covid-19 related distress among healthcare workers: Findings from a low caseload country under lockdown.

OBJECTIVES: To characterize psychological distress and factors associated with distress in healthcare practitioners working during a stringent lockdown in a country (Jordan) that had exhibited one of the lowest incidence rates of Covid-19 globally at the time of the survey. METHODS: A cross-sectional online survey sent to healthcare practitioners working in various hospitals and community pharmacies. Demographic, professional and psychological characteristics (distress using Kessler-6 questionnaire, anxiety, depression, burnout, sleep issues, exhaustion) were measured as were sources of fear. Descriptive and multivariable statistics were performed using level of distress as the outcome. RESULTS: We surveyed 937 practitioners (56.1% females). Approximately 68%, 14%, and 18% were nurses/technicians, physicians, and pharmacists (respectively). 32% suffered from high distress while 20% suffered from severe distress. Exhaustion, anxiety, depression, and sleep disturbances were reported (in past seven days) by approximately 34%, 34%, 19%, and 29% of subjects (respectively). Being older or male, a positive perception of communications with peers, and being satisfied at work, were significantly associated with lower distress. Conversely, suffering burnout; reporting sleep-related functional problems; exhaustion; being a pharmacist (relative to a physician); working in a cancer center; harboring fear about virus spreading; fear that the virus threatened life; fear of alienation from family/friends; and fear of workload increases, were significantly associated with higher distress. CONCLUSION: Despite low caseloads, Jordanian practitioners still experienced high levels of distress. Identified demographic, professional and psychological factors influencing distress should inform interventions to improve medical professionals' resilience and distress likelihood, regardless of the variable Covid-19 situation.

Development of a Physiologically-Based Pharmacokinetic (PBPK) Model of Nebulized Hydroxychloroquine for Pulmonary Delivery to COVID-19 Patients.

Despite inconclusive evidence, chloroquine (CQ) and hydroxychloroquine (HCQ)are commonly used for the treatment of Corona virus Disease 2019(COVID-19) in critically ill patients.It was hypothesized that HCQ as an aerosol application can reach the antiviral concentration of ~1-5 µM in the alveolar cells which has been proven effective in vitro. A physiologically-based pharmacokinetic (PBPK) model of nebulized HCQ for pulmonary delivery to COVID-19 patients using the Nasal-Pulmonary Module in GastroPlus® V9.7 simulator, in order to calculate the necessary inhalation dose regimen of HCQ, was developed. The physiological, drug disposition, and pharmacokinetic parameters were obtained from the literature and used during model building after optimization using Optimization Module, while oral data was used for validation. The 25 mg BID inhalation dosing was predicted to lead to alveolar HCQ levels of 7 µM (above EC50 of ~1-5 µM), and small plasma levels of 0.18 µM (as compared to plasma levels of 3.22 µM after 200 mg BID oral dosing). However, average contact time (>1 µM) is around 0.5 h in lung parts, suggesting indirect exposure response effect of HCQ.The developed PBPK model herein predicted HCQ levels in plasma and different lung parts of adults after multiple inhalation dosing regimens for 5 days. This in-silico work needs to be tested in vivo on healthy subjects and COVID-19 patients using 12.5 mg BID and 25 mg BID inhalation doses.