key: cord-1037854-1t38kxw5 authors: Alharbi, Naif Khalaf; Al-Tawfiq, Jaffar A.; Alghnam, Suliman; Alwehaibe, Amal; Alasmari, Abrar; Alsagaby, Suliman A.; Alsubaie, Faisal; Alshomrani, Majid; Farahat, Fayssal M.; Bosaeed, Mohammad; Alharbi, Ahmad; Aldibasi, Omar; Assiri, Abdullah M. title: Outcomes of Single Dose COVID-19 Vaccines: Eight Month Follow-up of a Large Cohort in Saudi Arabia date: 2022-04-06 journal: J Infect Public Health DOI: 10.1016/j.jiph.2022.04.001 sha: a51cb0643893743dbe90123bd8494c57b65ba315 doc_id: 1037854 cord_uid: 1t38kxw5 BACKGROUND: Two vaccines for COVID-19 have been approved and administered in the Kingdom of Saudi Arabia (KSA); Pfizer-BioNtech BNT162b2 and AstraZeneca-Oxford AZD1222 vaccines. The purpose of this study was to describe the real-world data on the outcome of single dose of these COVID-19 vaccines in a large cohort in KSA and to analyse demographics and co-morbidities as risk factors for infection post one-dose vaccination. METHODS: In this prospective cohort study, a total of 18,543 subjects received one dose of either of the vaccines at a vaccination centre in KSA, and were followed up for three to eight months. Data were collected from three sources; clinical data from medical records, adverse events (AEs) from a self-reporting system, and COVID-19 infection data from the national databases. The study was conducted during the pandemic restrictions on travel, mobility, and social interactions. RESULTS: The median age of participants was 33 years with an average body mass index of 27.3. The majority were males (60.1%). Results showed that 92.17% of the subjects had no COVID-19 infection post-vaccination as infection post-vaccination was documented for 1452 (7.83%). Diabetes mellitus (p=0.03), organ transplantation (p=0.02), and obesity (p<0.01) were associated with infection post-vaccination. Unlike vaccine type, being Saudi, male, or obese was associated with the occurrence breakthrough infections more than other parameters. AEs included injection site pain, fatigue, fever, myalgia, headache and was reported by 5.8% of the subjects. CONCLUSION: Single dose COVID-19 vaccines showed a protection rate of 92.17% up to eight months follow-up in this cohort. This rate in AZD1222 was higher than what have been previously reported in effectiveness studies and clinical trials. Obese, male, and Saudi were at higher risk of contracting the infection post-vaccination, Saudi and male might have more social interaction with the public when mobility and social interactions were limited during the pandemic. Side effects and AEs were within what has been reported in clinical trials. 2 were collected from three sources; clinical data from medical records, adverse events (AEs) from a self-reporting system, and COVID-19 infection data from the national databases. The study was conducted during the pandemic restrictions on travel, mobility, and social interactions. The median age of participants was 33 years with an average body mass index of 27.3. The majority were males (60.1%). Results showed that 92.17% of the subjects had no COVID-19 infection post-vaccination as infection post-vaccination was documented for 1452 (7.83%). Diabetes mellitus (p=0.03), organ transplantation (p=0.02), and obesity (p<0.01) were associated with infection post-vaccination. Unlike vaccine type, being Saudi, male, or obese was associated with the occurrence breakthrough infections more than other parameters. AEs included injection site pain, fatigue, fever, myalgia, headache and was reported by 5.8% of the subjects. , which was declared as a global pandemic (1-3). SARS-CoV-2 is highly contagious and transmitted through human-to-human contact (4) . Most COVID-19 cases (81%) are asymptomatic or present with mild to moderate symptoms (5) . However, J o u r n a l P r e -p r o o f 3 other cases are severe (14%) to critical (5%); with a case fatality rate of 2-3% (6) . As of September 2021, more than 222 million confirmed cases of COVID-19 and 4.5 million deaths were reported globally (7) . To reduce the risk of SARS-CoV-2 transmission, preventive strategies have been implemented, including the use of face masks, hand washing/hygiene, contact tracing, travel bans, and government-led cancellation of unnecessary activities (8) . Importantly, prophylactic vaccines are sought as the ultimate intervention to bring the pandemic under control. Over 200 vaccine candidates for COVID-19 were at various stages of clinical development (9) . Of these, at least 50 candidate vaccines have been evaluated in clinical trials and several vaccines have been approved by regulatory authorities, based on demonstrated safety profile and acceptable efficacy rates (10) . COVID-19 vaccine efficacy, in phase III clinical trials, were 95% for the Pfizer-BioNtech BNT162b2 vaccine, 92% for the Gamaleya SputnikV vaccine, 94.5% for Moderna mRNA-1273 vaccine, 70% for the AstraZeneca-Oxford AZD1222 vaccine, and 97% for Sinopharm BIBP COVID-19 vaccine (10) (11) (12) . Three of these vaccines were approved for emergency use by a number of international regulators, including the Saudi FDA, at the end of 2020. Accordingly, Kingdom of Saudi Arabia (KSA) was among the first countries to launch an accelerated program for COVID-19 vaccination (13, 14) . For each vaccine, there were a number of vaccine controlled randomised clinical trials focusing on evaluating safety, immunogenicity, and efficacy (10, 15) , which were the basis for regulatory approvals. However, to gain a better understanding of how COVID-19 vaccines would perform in various populations, it is essential to gather real-world data and analysis post-vaccination, particularly in different ethnic populations and other sub-populations. These sub-populations can be defined based on differences in gender, age, nationality, occupation, and comorbidities. In this prospective cohort study, data for 20,555 vaccinated subjects were collected from a were excluded from the analysis. Therefore, 18543 out of 20555 subjects were included in the study analysis. Subjects were followed up for at least three months (last vaccination was on the 14 th April 2021 and last follow up was on the 10 th August, 2021). Descriptive statistics were applied to summarise the data of subjects' demographical and clinical characteristics and the number of AEs. Comparisons between the two study groups ( Out of 18543, 17091 (92.17%) remained uninfected post-vaccination while SARS-CoV-2 infection was documented for 1452 (7.83%) vaccinated individuals (Table 1) . Forty-six (11.2% of those who received BNT162b2) and 1406 (7.75% from those who received AZD1222) had the infection post two weeks of the single dose vaccination, indicating the protection rate of these vaccines, Table S1 . Age was similar in the two groups of vaccinated subjects (uninfected and To identify risk factors associated with infection post-vaccination, we analysed comorbidity data of subjects in the two groups (Table 1) . Male gender and Saudi nationality appeared to be associated with infection post-vaccination than female and non-Saudi nationality (p<0.01). Diabetes (p=0.03), organ (mainly kidney) transplantation (p=0.02), and obesity (p=0.0014) were found to be associated with the risk of infection in vaccinated subjects. Remarkably, lung diseases, asthma, or cancer, for which treatment by chemotherapy predisposes patients to microbial infection due to leukocytopenia, did not affect the likelihood of infection among vaccinated subjects. Regression analyses showed that being Saudi, male, or obese is associated with contracting the infection post a single dose of COVID-19 vaccines ( Table 2 ). The data showed that the time however, the number of BNT162b2 vaccinees was small (n=410) with a smaller number of COVID-19 cases post BNT162b2 vaccine (only 46 cases). In addition, these times were not different with regard to subject comorbidities (Table S2) . Only 1084 subjects utilised the online reporting portal or contacted the hospitals to report AEs, 5.8% (Table 3) . Injection site pain was the most frequently reported AE (800 cases). Other common AEs include fatigue (732 cases), fever (714 cases), myalgia (678), headache (657 cases), joint pain and malaise (399 cases). In contrast, AEs, such as skin rash, cough, abdominal pain and tachycardia were only reported by single individuals among vaccinated subjects. 2020 and Mar. 2021 in the USA (17) . It was also found that most breakthrough infections (that occur post-vaccination) were either asymptomatic or mildly symptomatic (18) . In previous studies, the rate of breakthrough infections was not different among vaccinees by age group, gender, or type of vaccine, but it was lower among those without comorbidities (0.44 [95% CI 0.25,0.62]) compared with those with 1 to 3 comorbidities (19) . Diabetic patients are generally at higher risk of severe COVID-19 and increased mortality (20) . In the current study, infections were significantly higher in subjects with diabetes mellites, obesity, or organ transplantation. The contribution of underlying diseases to breakthrough infections is important as additional boosting doses are being recommended by regulators and health officials globally. The immune responses after COVID-19 vaccine were lower among those with underlying comorbidities such as diabetes mellitus, hypertension and renal disease (21) , which could partially explain the occurrence of breakthrough infections. It should also be considered that the rate of COVID-19 cases varies across time, which would certainly influence our findings and any effectiveness study. The coverage of vaccines against different variants is also variable; J o u r n a l P r e -p r o o f therefore, the rate of breakthrough infections might be different in different times and location according to case rate and circulating variants. Therefore, long-term follow-up on the vaccinees is needed to estimate the longevity of the single dose vaccine effectiveness. Furthermore, a regression analysis of the present data showed that Saudis, males, and obese subjects were associated with contracting the infection post-vaccination more than other groups. It is possible that Saudi males are at a higher rate of infections in general due to social norms, occupations, and behavioural interactions; thus, further social-epidemiological studies are warranted as differences in infections across nationalities or ethnicities have been reported previously (22) (23) (24) . Of the vaccinated subjects, only 5.8% reported AEs post-vaccination unlike a previous study from KSA where 34.7% reported AEs (25) . However, lack of reporting does not indicate lack of AE occurrence; and the difference in AE rate might be related to the methodology. The current study was based on self-reporting while the previous study utilised an active method by calling subjects and recording AEs. In the current study, the most reported AEs were injection site pain, fatigue, fever, myalgia, and headache. Injection site pain was the most common AE post AZD1222 (30.5%) vaccination in the previous local study (16) while it was not possible to establish a rate for this AE in the current study due to the used method. Injection-site pain was reported by 48.6% (26) in phase III clinical trials; however, it varied depends on the vaccine type (27) . Fever was the most frequently reported adverse effects after COVID-19 vaccination in this study. It was reported in 18.5% after the first dose, 1.3% after the second dose of BNT162b2 vaccine in KSA (28) . This rate was 31% after the AZD1222 vaccine (16) , but was 66% after either AZD1222 or BNT162b2 vaccine in another study (29) . In clinical trials, fever was reported in 22% of participants receiving BNT162b2 vaccine (30) . The current study showed that seven vaccinees had lymphadenopathy after COVID-19 vaccination. The incidence of ipsilateral axillary reactive lymphadenopathy following mRNA vaccine was 13% among 68 patients who had CT-scan (31) . The estimated occurrence of lymphadenopathy was 1% and 10% after the after BNT162b2 and mRNA-1273 vaccines, respectively (32, 33) . Nevertheless, lymphadenopathy is usually documented following other intramuscular vaccines such as influenza and human papillomavirus vaccines (34) (35) (36) The current study is based on a single centre, which may limit its generalizability. It did not include AEs from all those who were vaccinated, which does not allow for establishing an accurate incidence rate of AEs post-vaccination. The included vaccinees only received one dose, making it impossible to extrapolate the findings to the recommended two-dose regimen, which has now been completed in many individuals in KSA. Despite these limitations, the study provides an early and significant finding of the outcomes of a single dose COVID-19 vaccination that might be sought where vaccine supply is short. The study also provokes the need for further studies on risk factors for post-COVID-19 vaccination breakthrough infections such as gender and obesity. This study is the first to investigate the safety and protection outcomes of two main vaccines in a large cohort in Saudi Arabia including national and expatriate subjects from different countries. Single dose COVID-19 vaccines showed a protection rate of 92% with no major side effects during the three to eight months observational period. Obese, male, and Saudi were at higher The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance Novel human coronavirus (SARS-CoV-2): A lesson from animal coronaviruses COVID-19 in early 2021: current status and looking forward Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention COVID-19) Dashboard SARS-CoV-2 and the pandemic of COVID-19 Looking beyond COVID-19 vaccine phase 3 trials Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous primeboost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial Phase 1-2 Trial of a SARS Recombinant Spike Protein Nanoparticle Vaccine An mRNA Vaccine against SARS-CoV-2 -Preliminary Report Launching COVID-19 vaccination in Saudi Arabia: Lessons learned, and the way forward Interim guidelines for the use of SARS-CoV-2 vaccine Riyadh, Saudi Arabia Public Health Authority The effectiveness of the TWO-DOSE BNT162b2 vaccine: analysis of real-world data Safety and Reactogenicity of the ChAdOx1 (AZD1222) COVID-19 Vaccine in Saudi Arabia Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers -Eight U.S. Locations Covid-19 Breakthrough Infections in Vaccinated Health Care Workers Rate and risk factors for breakthrough SARS-CoV-2 infection after vaccination BNT162b2 COVID-19 vaccine and correlates of humoral immune responses and dynamics: a prospective, single-centre, longitudinal cohort study in health-care workers Diabetes as a risk factor for greater COVID-19 severity and in-hospital death: A meta-analysis of observational studies COVID-19 disparity among racial and ethnic minorities in the US: A cross sectional analysis Prevalence and fatality rates of COVID-19: What are the reasons for the wide variations worldwide Efficacy of Single dose Ad26.COV2.S Vaccine against Covid-19 Comparative systematic review and meta-analysis of reactogenicity, immunogenicity and efficacy of vaccines against SARS-CoV-2. NPJ vaccines Minor to Moderate Side Effects of Pfizer-BioNTech COVID-19 Vaccine Among Saudi Residents: A Retrospective Cross-Sectional Study Evaluation of Side Effects Associated with COVID-19 Vaccines in Saudi Arabia Side effects of BNT162b2 mRNA COVID-19 vaccine: A randomized, cross-sectional study with detailed self-reported symptoms from healthcare workers Association of COVID-19 mRNA Vaccine With Ipsilateral Axillary Lymph Node Reactivity on Imaging Acute onset supraclavicular lymphadenopathy coinciding with intramuscular mRNA vaccination against COVID-19 may be related to vaccine injection technique The European Medicines Agency (EMA). Summary of product characteristics -COVID 19 vaccine Moderna Axillary lymph node accumulation on FDG-PET/CT after influenza vaccination Lymph Node Activation by PET/CT Following Vaccination With Licensed Vaccines for Human Papillomaviruses