Follow-up of Covid-19 Vaccinated Pregnant and/or Breastfeeding Women in Tunisia: An International Journal of Medical Toxicology and Drug Experience

Introduction: Initially, vaccination against Covid-19 was not recommended during pregnancy due to the lack of data. With the benefit of hindsight, it has become recommended. This decision followed the reassuring results from pregnant women who voluntarily or inadvertently received Covid-19 vaccines, especially with mRNA vaccines [1]. In Tunisia, from May 2021, pregnant women have been prioritized in the national vaccination program with the recommendation of the messenger RNA platform. Objective: To follow-up Covid-19 vaccinated pregnant and/or breastfeeding women in Tunisia. Methods: We have started a pilot study (from September 2021 to April 2022) for monitoring pregnant and/or breastfeeding women. Data collection was carried out via telephone calls. We excluded women who were unreachable after two phone calls. The data collected concerned the course as well as the outcome of the pregnancy and the health status of newborns. In addition, women were asked about the possible occurrence of adverse effects following immunization. Results: Our study included 1253 women. Seventeen percent of them were previously infected with Covid-19. The vaccination schedule was complete (two doses) in 83% of cases. Pfizer-BioNTech vaccine (PBV) was used in 73% of cases (11% of cases in the first trimester, 42% in the second trimester and 19% in the third trimester) and Moderna vaccine in 26%. Coronavac vaccine was used in 1% of cases. Vaccination was performed during pregnancy in 74 % of cases and breastfeeding in 11% of cases. Fifteen percent of women received the first dose during pregnancy and the second dose after childbirth. Reported adverse events following vaccination were: pain at the injection site in 47%, fever in 23%, soreness in 15%, asthenia in 6%, headache in 5%, hot flashes in 3% and chills in 1% of cases. Pregnancy and breastfeeding outcomes were favourable in 1246 women (99.4% of cases). Forty-seven percent of women delivered at term without incident and newborns were apparently in good health. One case of spontaneous miscarriage was reported in a woman with a history of spontaneous abortion and Covid-19 infection two weeks after receiving the first dose of PBV. Six cases of neonatal jaundice were also reported with PBV with good evolution with phototherapy. Conclusion: Our study confirms the data in the literature concerning the safety of Covid-19 vaccines on pregnant and/or breastfeeding women.

Adverse Reactions Associated with Comirnaty® Among Healthcare Professionals: A Cohort Event Monitoring Study in a Portuguese Hospital: An International Journal of Medical Toxicology and Drug Experience

Introduction: The Portuguese government put into practice a vaccination plan soon after the approval of the first COVID-19 vaccine, prioritizing healthcare professionals (HCPs) and other population groups at risk. Objective: To characterize the case reports of adverse drug reactions (ADRs) associated with the administration of Comirnaty to HCPs in a Portuguese oncology hospital (IPO Coimbra). Methods: This study was a nine-month prospective, observational study following a cohort event monitoring approach focused on signalling ADRs associated with the administration of Comirnaty to HCP in IPO Coimbra. The case reports of ADRs were sent to the Pharmacovigilance Unit of Coimbra (UFC) between 14/01/2021 and 13/10/2021. The population of HCP was characterized according to gender and age distribution. The seriousness of ADRs was assessed for each individual case in accordance with WHO criteria [1]. ADRs were coded with MedDRA version 24.0 (System Organ Classification [SOC] and Preferred Term [PT]). ADRs were classified as expected or unexpected according to their description in the Summary of Product Characteristics (SmPC) of Comirnaty [2]. Results: A total of 816 HCPs were inoculated with at least one dose of Comirnaty. The case reports of ADRs concerned 469 (57.5%) HCPs: 386 (82.3%) females;642 (78.7%) aged 30-59 years old. Of the 469 case reports, 24 (5%) were assessed as serious, 44 (9.4%) as unexpected, and 11 (2.3%) as both serious and unexpected. The 469 case reports contained a total of 1,955 ADRs. "General disorders and administration site condition" (n = 1,075;54,9%), such as vaccination site pain, chills and vaccination site swelling;"Musculoskeletal and connective tissue disorders" (n = 373;19.1%), including myalgia and arthralgia;and "Nervous system disorders" (n = 250;12.8%), including headache, were the most frequently reported ADRs, which is in line with the SmPC of Comirnaty®. The 11 case reports classified as both serious and unexpected contained a total of 17 ADRs, including hyperhidrosis and paraesthesia. Conclusion: The results of this study bring value to the characterization of the safety profile of Comirnaty® since the use of a cohort of individuals allows to estimate frequencies of ADRs in the real-world. Further, serious, and unexpected ADRs were identified. Importantly, this type of safety data was further included in the SmPC of the vaccine. In conclusion, the results are in favour of the positive benefitrisk ratio of Comirnaty®, and reinforce the importance of post-marketing pharmacovigilance to increase knowledge on drug safety.

Rates of ADR Reports by Number of Administered SARS-CoV-2 Vaccination Doses in Sweden: Large Temporal Variations Especially in Consumer Reporting: An International Journal of Medical Toxicology and Drug Experience

Introduction: During the SARS-CoV-2 vaccinations in 2021, a record number of Individual Case Safety Reports (ICSR) were submitted to the Swedish Medical Products Agency (MPA). MPA further initiated a record-linkage study [1] by which vaccination data from the National Vaccination Register (NVR) was made accessible. Objective: We aimed at identifying temporal variations in reporting rates of ICSRs by number of administered vaccine doses, and if found, seek plausible explanations to them. Methods: The weekly number of ICSRs submitted to the MPA was divided by the weekly number of administered doses between December 27, 2001, and May 1st, 2022, resulting in the reporting rate per 1,000 doses and week. Results: A total of 102,798 submitted ICSRs and 21.9 million administered doses resulted in an overall reporting rate of 4.7 ICSRs per 1000 doses, range: 0.9/1000 (April 2022) to 21.3/1000 (March 2021). Eighty-two percent of the reports were submitted by consumers. A four-fold increase in reporting rate was observed between weeks 5 and 11, 2021. This coincided with the start of vaccination of prioritized health-care personnel and ensuing mass media activity on e.g. whole hospital wards having to close due to the personnel's flu-like symptoms (fever, headache, fatigue, chills, etc.) following vaccination. On March 16, the Public Health Agency of Sweden decided that only individuals aged 65 or older would receive the Astra Zeneca AZD1222 vaccine. This was followed by a steep seven-fold decline in reporting in three weeks. Reporting rates from both health-care professionals and consumers increased and decreased in a similar fashion. During the summer of 2021, additional peaks in reporting rates were observed. At the same time, menstruation disorders following vaccination were debated in both social and traditional media. The most recent decline in reporting rates, which has yet to turn to an increase, occurred after the Russian invasion of Ukraine in the end of February 2022. The fluctuating reporting rates observed since April 2021 and onwards were almost exclusively seen in consumer reports. Conclusion: Rates of submitted spontaneous reports per 1.000 vaccinations in Sweden varied markedly during the studied period, the most pronounced of which originated from changes in consumer reporting. Many peaks in reporting rates can be-at least temporally-associated to various media or world events, even if a causal relationship can't be proven.

Systemic COVID-19 vaccines Adverse Events Following Immunizations and Their Associated Factors: A Comparative Study Using Iraqi Consumers' Self-Reported Data: An International Journal of Medical Toxicology and Drug Experience

Introduction: Three types of COVID-19 vaccines were deployed in Iraq;PfizerBioNTech, AstraZeneca, and Sinopharm. Spontaneous self-reported safety data received directly from consumers was an important source of COVID-19 vaccine reporting sources for the first time in Iraq. Objective: To study the common systemic AEFIs and factors influencing them, using self-reported data by Iraqi consumers vaccinated with different COVID-19 vaccine types. Methods: As a part of the national plan for COVID-19 vaccines safety surveillance, an online self-assessment form was designed by the national pharmacovigilance center for the public consumers across the country. The form was quadrilingual and captures the necessary information for a valid AEFI report. Demographic data, contact details, vaccination details, adverse event information, and medical history were collected. To facilitate the filling process and standardize the answers, a list of predefined common short-term AEFIs were included as a checklist, in addition to a free text for other unlisted AEFIs. A retrospective cross-sectional study using the collected responses from April, 2021 until April, 2022 was performed. Data was validated and cleaned. Analyses was performed using SPSS software version 26. Selected common short-term AEFIs were analysed. The incidence of these AEFIs were compared between vaccine types using chisquare test. Moreover, predictors of reporting these AEFIs were explored using binary logistic regression for each vaccine type. Results: A total of 2843 report were included, 62.0% of them were male. The age mean was 36.33 (SD ± 12.2). The participants were more likely to report after the 1st dose (79.4%). AstraZeneca vaccine was found to produce the highest number of AEFIs per report, 4.31 (SD ± 2.4). AstraZeneca and PfizerBioNTech were significantly associated with a higher incidence of multiple AEFIs as compared with Sinopharm (fatigue, joint pain, headache, fever, and chills). PfizerBioNTech vaccine was associated with 71 out of the 76 reported lymph nodes AEFIs. Factors that were significant predictors of higher reporting of systemic AEFIs were;for PfizerBioNTech (female gender, increased dose number, and increased likelihood of previous COVID-19 infection);AstraZeneca (younger age, female gender, and increased likelihood of previous COVID-19 infection);and in case of Sinopharm (younger age, and female gender) Conclusion: The results showed that AstraZeneca and Pfi-zerBioNTech vaccines were associated with more AEFIs than Sinopharm. Predictor factors of AEFIs include;female gender in all vaccines;the presence of previous COVID-19 infection in both PfizerBioNTech and AstraZeneca vaccines;second dose in PfizerBioNTech;and younger age for both AstraZeneca and Sinopharm.

Oral Presentation: Adverse Events to COVID-19 Vaccines and Policy Considerations that Inform the Funding of Safety Surveillance in Low- and Middle-Income Countries: An International Journal of Medical Toxicology and Drug Experience

Introduction: As of April 3, 2022, 31 COVID-19 vaccines had received approval for use globally (1). With the fast-tracked development and concurrent introduction of vaccines in all countries, there is a need for equitable safety surveillance to monitor adverse events following immunization (AEFIs) in high-income and low- and middle-income countries (LMICs). Objective: To profile the AEFIs to COVID-19 vaccines, explore the difference in reported AEs between Africa and the rest of the world (RoW), and understand the policy considerations that inform the decision by funding organizations to strengthen safety surveillance systems in LMICs. Methods: We used a convergent mixed methods design involving secondary analysis of 14,671,586 AEFIs to COVID-19 vaccines reported to VigiBasea by countries in the WHO Africa Region and the RoW between December 2020 and March 2022. The qualitative component consisted of 12 in-depth interviews with key policymakers from some donor/funding organizations. Results: With 87,351 out of 14,671,586 total reported AEFIs to COVID-19 vaccines (0.6%) Africa had the second-lowest crude AEFI reporting rate of 180 AEs per 1million administered doses. Reports from females made up 73.6% of reports from African and RoW compared to 24.4% for males. The highest number of reports came from persons 18-44 years. 26.0% of the reports were serious, with death being the reason for seriousness in 5% of the reports. Statistically significant differences in AEFI reporting by gender, age group, and serious AEs were found between Africa and the RoW. AstraZeneca, PfizerBioNtech, and Janssen vaccines were the most frequently associated with AEFIs in terms of the absolute number of AEs for Africa and RoW. Sputnik V contributed the highest percentage of AEs per vaccine for Africa. Headache, pyrexia, injection site pain, dizziness, and chills were the top 5 reported AEs for Africa and RoW. Qualitative findings revealed decisions of many funding organizations to fund safety surveillance in LMICs were influenced by considerations about country priorities, the perceived utility of the evidence generated for local decision making, and the contributions to global health by safety surveillance systems. Conclusion: Countries in Africa reported fewer AEFIs to COVID-19 vaccines in VigiBase relative to the RoW, with statistically significant differences in reporting of key parameters that warrant further investigation. Funding decisions by donor organizations were influenced by country priorities and the perceived value added by data generated from safety surveillance systems in LMICs to local and global decision making.

Safety Profile of Tyrosine Kinase Inhibitors Approved for Gastrointestinal Stromal Tumors: Analysis from the European Spontaneous Adverse Event Reporting System: An International Journal of Medical Toxicology and Drug Experience

Introduction: Gastrointestinal stromal tumors (GISTs), soft tissue sarcomas of the digestive tract, are associated with oncogenic mutations that led to the approval of tyrosine kinase inhibitors (TKIs) [1-2]. Considering the increased use of TKIs in clinical practice, it may be useful to identify unexpected adverse drug reactions (ADRs). Objective: The aim of this study was to describe better ADRs and to identify unexpected potential safety signals through the analysis of individual case safety reports (ICSRs) among TKIs approved for GIST collected into the European Spontaneous Reporting System (SRS) database. Methods: All ICSRs recorded starting from the drug approval up to 31 December 2021 with one of the following TKIs reported as suspected drug were included: imatinib (IM), sunitinib (SU), avapritinib (AVA), regorafenib (REG), and ripretinib (RIP). A descriptive analysis was conducted to assess all demographic characteristics. Moreover, a disproportionality analysis was performed using the Reporting Odds Ratio (ROR) with the corresponding 95% Confidence Interval (CI) to evaluate the frequency of ADRs for each TKI compared to all other TKIs. Results The number of analyzed ICSRs was 8,512 (Figure 1 Flowchart of ICSRs selection process): the 57.9% were related to IM, followed by SU (24.2%), AVA (13.1%), REG (2.7%), and RIP (2.1%). ICSRs were mainly serious (87.5%), related to males (51.7%), and to adults (44.7%);moreover, the 25.5% were fatal. The disproportionality analysis showed a higher reporting frequency of some unexpected ADRs for each TKI: gait disturbance (ROR 2.86;95% CI 1.90-4.29), hyperhidrosis (2.57;1.06-6.20), and hyperammonemia (3.92;1.05-14.60) for SU;cerebrovascular accident (6.23;2.18-17.84), hemoglobin decreased (2.23;1.08-4.61), and internal haemorrhage (14.44;3.94-52.92) for RIP;gastrointestinal ulcer (10.88;2.98-39.81) for REG;hepatic and lung cancer for IM (12.79;8.04-20.37 and 7.71;3.33-17.84, respectively);hallucination (24.33;9.02-65.68), mood swings (8.02;2.44-26.33), and stress (6.68;1.93-23.11), nephrolithiasis (6.69;2.15-20.77), pollakiuria (3.08;1.17-8.13), and dialysis (6.68;1.67-26.73), sinusitis (3.34;1.14-9.78), cellulitis (4.17;1.36-12.78), and COVID-19 (7.25;3.40-15.45), chills (2.36;1.22-4.58), limb fracture (3.53;1.63-7.60), hernia (9.23;3.71-23.00), diabetes mellitus (5.02;2.11-11.95), hyposideraemia (5.02;2.11-11.95), tinnitus (3.64;1.34-9.87), parosmia (5.00;1.12-22.38), Raynaud's phenomenon (5.00;1.12-22.38), and thyroid function test abnormal (8.90;1.99-39.83) for AVA. Conclusion: This study is largely consistent with results from literature but some unexpected ADRs were shown. Further studies are necessary to increase the awareness about the safety profiles of new TKIs approved for GISTs.

CHILAIDITI SYNDROME IN A 49-YEAR-OLD MALE WITH COVID-19 INFECTION – CASE REPORT

The authors illustrate a case of a 49-year-old male patient admitted to our Emergency Department with dry persistent cough, fever, chills, vague abdominal discomfort and a recent history of dyspnoea and fatigability, symptoms suggestive of COVID-19 infection. Physical examination showed mild abdominal distension and no signs of peritoneal irritation. The patient was tested positive for COVID-19 and d-dimers were also found positive, raising a strong suspicion diagnosis of pulmonary thromboembolism as a complication of SARS-COV-2 infection, which required an immediate CT scan. No signs of pulmonary thromboembolism were present on the CT scan. Apart from bilateral pulmonary condensation areas having a ground glass pattern with a peripheral distribution, which are the characteristic radiologic feature of SARS-COV-2 infection, the CT scan also revealed the anterior interposition of the colon between the liver and diaphragm, this being highly suggestive for Chilaiditi Syndrome.

A review on corona virus pandemic: Update on epidemiology, diagnosis, and treatment

Coronavirus, at present, has created major health havoc across the world. It has been declared as a global health threat by the World Health Organization (WHO). The world has already experienced major outbreaks of coronaviruses previously. A few of the major outbreaks from the past include Severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, Middle East Respiratory Syndrome (MERS-CoV) in 2012, and the present Severe acute respiratory syndrome coronavirus 2(SARS-CoV-20). All of these belonged to Coronaviridae and have been known to cause respiratory infections mostly. The infection ranges from mild to severe and even death with common symptoms of fever, chills, shortness of breath, gastrointestinal problems, etc. This respective review article discusses the prominent members of Coronaviridae in detail. It highlights the major outbreaks of coronaviruses faced by the world and the substantial mortalities caused by them. It also talks about the most effectively used methods of diagnosis for such viruses andenumerates the antivirals and drug combinations found effective against the past and present coronavirus infections. Coronavirus is at present the hottest topic for study due to COVID-19. This review article aims to collectively present all the relevant data for our readers which can help them to strengthen their basic knowledge for future studies.

A Case of a COVID-19-positive Patient.

The coronavirus (COVID-19), discovered in 2019, has been creating havoc since it first emerged in China and is now spreading worldwide. Its presentation is somewhat similar to influenza. We hereby discuss the salient features of the coronavirus and present the case of a 33-year-old male who was tested positive for COVID-19.