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The Impact of Vaccination Against SARS-CoV-2 Virus on the Outcome of COVID-19 Disease

Authors AlKhafaji DM, Al Argan RJ , AlBahrani S, Alwaheed AJ , Alqatari SG , Al Elq AH , Albaker W, Alwazzeh M, AlSulaiman AS, AlSulaiman RS , Almadan HM, Alhammad AA , Almajid AN , Hakami FH, Alanazi WK

Received 12 March 2022

Accepted for publication 9 June 2022

Published 2 July 2022 Volume 2022:15 Pages 3477—3489

DOI https://doi.org/10.2147/IDR.S365179

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Suresh Antony



Dania M AlKhafaji,1 Reem J Al Argan,1 Salma AlBahrani,2 Abrar J Alwaheed,1 Safi G Alqatari,1 Abdulmohsen H Al Elq,1 Waleed Albaker,1 Marwan Alwazzeh,1 Amal S AlSulaiman,1 Reem S AlSulaiman,1 Hussain M Almadan,1 Ali A Alhammad,1 Ali N Almajid,1 Fatimah H Hakami,2 Wafa K Alanazi2

1Department of Internal Medicine, College of Medicine-Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, Khobar, Eastern Province, Saudi Arabia; 2Department of Internal Medicine, King Fahad Military Medical Complex, Dhahran, Eastern Province, Saudi Arabia

Correspondence: Reem S AlSulaiman, King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia, Tel +966 533229610, Email [email protected]

Background: Coronavirus disease 2019 (COVID-19) is a rapidly spreading infection that is on the rise. New variants are continuously appearing with variable degrees of lethality and infectivity. The extensive work since the start of the pandemic has led to the evolution of COVID-19 vaccines with varying mechanisms. We aim to determine real-world data by looking at the different clinical outcomes associated with COVID-19 vaccination, focusing on the rate of hospitalization, severity, and mortality.
Methodology: A retrospective observational study included 624 patients with COVID-19 infection who were hospitalized at King Fahad Hospital of the University and King Fahad Military Medical City between April and July 2021. The cohort was divided into 3 groups: unvaccinated, partially vaccinated (PV), and fully vaccinated (FV). The severity and outcome of COVID-19 disease were compared among the three groups. Among the vaccinated group, we studied the effect of vaccine type on the severity and outcome of COVID-19 disease.
Results: We found that 70.4% of patients with COVID-19 disease who required hospitalization were unvaccinated. Un-vaccination was a significant predictor of critical COVID-19 disease (OR 2.31; P < 0.001), whereas full vaccination was associated with significantly milder disease severity (OR 0.36; P 0.01). Moreover, un-vaccination status was an independent predictor of longer hospitalization (OR 3.0; P < 0.001), a higher requirement for ICU admission (OR 4.7; P < 0.001), mechanical ventilation (OR 3.6; P < 0.001), and death (OR 4.8; P < 0.001), whereas the FV group had a lower risk of ICU admission (OR 0.49; P 0.045). Unvaccinated patients with comorbidities had worse severity and outcome of COVID-19 infection (P< 0.05). Both vaccine types (Pfizer and AstraZeneca) had similar protective effects against the worst outcomes of COVID-19 disease.
Conclusion: COVID-19 vaccination has been shown to be effective in reducing hospitalization, the severity of COVID-19 infection, and improving outcomes, especially in high-risk group patients. COVID-19 vaccination programs should continue to improve the outcome of such a disease.

Keywords: COVID-19 disease, COVID-19 vaccine, severity, outcome, mortality

Introduction

Coronavirus disease 2019 (COVID-19) which was first detected in December 2019 and declared a pandemic by the World Health Organization (WHO) in March 2020, is still an emerging and rapidly spreading disease.1,2 The governments worldwide have done intense efforts to control the spread of the disease. However, there were new variants that have emerged over the last year with variable degrees of lethality and infectivity.3 The countries including the Kingdom of Saudi Arabia (KSA) have faced multiple COVID-19 waves. The Saudi Ministry of Health (MOH) has reported the beginning of 3rd wave in December 2021 which was posing a public health compromise.4 During the third wave, KSA has announced an average of 4000 cases per day and a peak number of 5928 cases per day on 19th January 2022.5 The critical cases have increased as well to reach 1000 cases at the date of preparing this report.4

Clinical features of COVID-19 disease are variable among the general population.6 It predominantly affects the pulmonary system, resulting in mild to critical disease.7 Critical cases could be complicated with acute respiratory distress syndrome (ARDS), respiratory failure, cytokine storm syndrome, and eventually death.7 As of February 2022, there have been a total of 8900 death rates in KSA due to COVID-19 infection.8

Vaccines enhance people’s immunity, improving and avoiding hazardous infections and death.9 It is estimated that vaccines have the potential to prevent 6 million deaths from vaccine-preventable diseases annually.9 As a result; there has been extensive work since the start of the COVID-19 pandemic to develop an effective vaccine. This resulted in the development of several vaccines like Pfizer BioNTech, AstraZeneca ChAdOx-S (Vaxzevria), Janssen Ad26.COV 2-S, Moderna mRNA-1273, Sinopharm BIBP, Sinovac biotech, Sputnik V, EpiVacCorona, CoviVac and Sputnik Light.10–12 As of 12th January 2022, WHO has approved some vaccines to be used in the COVID-19 vaccination program: Pfizer BioNTech, AstraZeneca ChAdOx-S, Janseen Ad26.COV 2-S, Moderna, Sinopharm, Covovax, Sinovac, Covaxin, and Nuvaxovid.13 Vaccine types, advantages, disadvantages, and doses are summarized in (Tables 1 and 2).

Table 1 COVID-19 Vaccine Types, Doses and Contraindications

Table 2 Advantages and Disadvantages of Different Types of COVID-19 Vaccines

Saudi Arabia applied the COVID-19 vaccination program initially with Pfizer-BioNTech after receiving Saudi FDA approval in December 2020 and subsequently, AstraZeneca ChAdOx-S in February 2021.14,15 Up to the date of writing this report, around 50 million vaccine doses have been given in KSA including the first and second doses.4 Initial randomized controlled trials at the time of testing vaccine efficacy have shown a positive effect against COVID-19 symptoms, severity, hospitalization, and death.10–12 Subsequently, there have been few population-based studies that showed similar results.11,16,24

However, real-world studies to evaluate the efficiency of the vaccine are scarce worldwide, specifically in Saudi Arabia. Therefore, such studies are warranted. As a result, this study will help to determine the different clinical outcomes associated with COVID-19 vaccination, focusing on the rate of hospitalization, COVID-19 severity, and outcome in terms of intensive care unit (ICU) admissions, related complications, and deaths. The findings will aid in raising awareness about vaccination and its impact on hospitalization and the outcome of COVID-19 disease.

Methodology

To investigate the role of COVID-19 vaccination on hospitalization rate and outcomes in patients infected with COVID-19, a retrospective observational study of 1080 patients admitted with COVID-19 infection to King Fahad Hospital of the University (KFHU) and King Fahad Military Medical City (KFMMC) between April and July 2021 was conducted.

Patients who were hospitalized with the first documented COVID-19 pneumonia at KFHU and KFMMC irrespective of their vaccination condition were included in the study. Patients under the age of 18, pregnant women, patients who tested positive for COVID-19 infection before April 2021, and patients who were hospitalized for a reason other than COVID-19 pneumonia and had an incidental positive RT-PCR for SARS-CoV2 were excluded. The inclusion and exclusion criteria were then implemented for 1080 patients. As a result, 624 patients were qualified to participate in the study.

Data Collection Procedure

Data were collected from the electronic medical records at KFHU and KFMMC. To categorize data into different parts, a data collection form was used. The first part dealt with demographic information, such as the patient’s age, gender, as well as nationality. The second part included the patient’s laboratory peak tests while hospitalized, which included complete blood count (CBC), renal function test (RFT), lactate dehydrogenase (LDH), inflammatory markers, D-dimer, and ferritin. The following part included grading of the severity of COVID-19 disease by Saudi Ministry of Health 2020 protocols7 into mild to moderate, severe, and critical disease. The criteria for grading different severity classes are presented in (Table 3). Next, we included the outcome of COVID-19 infection as measured by the length of hospitalization (LOH), the need for ICU admission, mechanical ventilation, and mortality. We used a cut-off of more than 7 days to define longer hospitalization which is correlated with the reported median duration of hospital stay in Saudi Arabia.17 The last part was about vaccination data including the type of the vaccine, number of doses, and the date of the last dose.

Table 3 Association of Severity and Outcome of COVID-19 with the Vaccination Status

The total population was then divided based on their vaccination status into three categories: unvaccinated, partially vaccinated (PV) (vaccinated with the first dose), and fully vaccinated (FV) (vaccinated with two doses). Next, the severity and outcome of COVID-19 infection in the three study categories were compared and analyzed. Finally, we examined the effect of the type of vaccine on the severity and outcome of COVID-19 infection.

Statistical Analysis

IBM SPSS was used to analyze the data. All categorical variables were shown as percentages and frequencies, while all continuous data was shown as the interquartile range (IQR) and median. The Fisher exact test or the Chi-square test were used to examine the relationship between variables, and the Kruskal Wallis test was used to compare the medians. A multivariate regression analysis was performed to eliminate the effect of other confounders and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A P-value less than 0.05 was used to determine statistical significance.

Ethics Approval and Consent to Participate

The study was approved by the Imam Abdurrahman Bin Faisal University (IRB-2021-01-261) and KFMMC (AFHER-IRB-2022-003) Institutional Review Board Committees. Confidentiality was maintained. Informed consent was not applicable or required from both centers’ IRB since it is a retrospective observational study. The research protocol is carried out by the applicable guidelines. Our study complies with declaration of Helsiniki.

Results

Demographics

A total of 624 patients were involved in this research, 352 (56.4%) of them were males and 272 (43.6%) were females. The majority 433 (69.4%) were older than 40 years of age. The most prevalent comorbidities were diabetes mellitus (DM) in 315 (50.5%) followed by cardiac diseases in 153 (24.5%) and respiratory disease in 56 (9%). The majority of our patients (66.2%) had 1–3 comorbidities. As shown in (Table 4) there was no significant difference in terms of age, gender, and comorbidities among vaccinated and unvaccinated patients (P > 0.05).

Table 4 Demographics

Vaccination Status

We have found that 439 (70.4%) of patients were unvaccinated and 185 (29.6%) were vaccinated. Out of 185 vaccinated cases, 146 (78.9%) were PV while 39 (21.1%) were FV. The complete distribution of vaccination status is presented in (Table 5).

Table 5 The Results of Vaccine Information

The Comparison of Laboratory Parameters Between the Three Study Groups

A comparison of laboratory parameters between the three study groups is presented in (Table 6). White blood cell (WBC) count was significantly more in unvaccinated patients compared to partially and fully vaccinated patients with a median of 12.2 (P 0.003) for the unvaccinated patients. In males, median hemoglobin was significantly lower in FV patients of 10.2 (P 0.027). Median lymphocyte count was significantly lower in the unvaccinated group of 1.5 (P 0.011), while neutrophils, CRP, and D-dimer were significantly higher in the unvaccinated group (P <0.05). LDH and ferritin were significantly higher in the PV group (P <0.05). All other parameters were statistically insignificant between the three study groups.

Table 6 Comparison of Laboratory Parameters Between Vaccinated and Unvaccinated Groups

Association of COVID-19 Disease Severity and Vaccination Status

The association between COVID-19 severity and vaccination status is presented in (Table 3). The results of this study depicted that the majority of unvaccinated patients had a higher risk of developing severe to critical disease of COVID-19 in 82.2% (P <0.001). Pneumonia on chest x-ray was seen in 84% of unvaccinated patients compared to 71.9% and 64.1% of patients who were partially and fully vaccinated, respectively (P 0.014). Respiratory rate greater than 30/minute was seen in 52.2% of unvaccinated patients versus 36.3% and 23.1% in partially and fully vaccinated patients, respectively (P 0.001). Among critical severity criteria, ARDS, sepsis, and cytokine storm syndrome were significantly higher in unvaccinated patients (P <0.001). The multivariate analysis illustrated that un-vaccination status was an independent predictor of critical COVID-19 disease (OR 2.31; P<0.001) while patients who were FV had a significantly milder COVID-19 disease (OR 0.36; P 0.01) (Table 7).

Table 7 Multivariate Analysis of the Association Between the Severity of COVID-19 with Age, Gender, Co-Morbidities, and Vaccination Status

Association of COVID-19 Disease Outcome and Vaccination Status

The unvaccinated group had a worse outcome in terms of longer hospital stay, more requirements for ICU admission, and mechanical ventilation (P <0.001). Likewise, mortality was higher in the unvaccinated group 21.5% compared to 5.5% in the PV and 5.1% in the FV groups (P <0.001) (Table 3). Multivariate analysis showed that un-vaccination status was an independent predictor of longer hospitalization OR 3.0 (P <0.001), higher need for ICU admission OR 4.7 (P <0.001), mechanical ventilation OR 3.6 (P <0.001), and death OR 4.8 (P <0.001). On the other hand, patients who were FV had a significantly lower need for ICU admission (OR 0.49; P 0.045) (Table 8).

Table 8 Multivariate Analysis of the Association Between Outcome of COVID-19 with Age, Gender, Co-Morbidities, and Vaccination Status

Association Between Severity of COVID-19 Infection with Age, Gender, and Co-Morbidities

Multivariate analysis demonstrated that older age was significantly linked to critical COVID-19 infection (OR 1.78; P 0.017). In addition, DM was significantly associated with both severe (OR 2.52; P 0.001) and critical (OR 3.18; P <0.001) COVID-19 disease (Table 7).

Association Between the Outcome of COVID-19 Infection with Age, Gender, and Co-Morbidities

The multivariate analysis illustrated that older age was significantly linked to a higher requirement of ICU admissions (OR 1.5; P 0.04) and longer hospital stay (OR 3.0; P <0.001). Additionally, the male gender was a predictor of mortality (OR 3.0; P < 0.001). In terms of comorbidities, patients with DM had a significantly higher risk of longer hospitalization (OR 1.9; P<0.001), ICU admission (OR 2.5; P<0.001), mechanical ventilation (OR 2.3; P<0.001), and death (OR 4.1; P<0.001). In addition, cardiac diseases were significantly associated with a higher rate of admission to ICU (OR 1.7; P 0.01), mechanical ventilation (OR 4.9 P<0.001), and death (OR 3.9; P<0.001) (Table 8).

The Effect of Vaccination Status on the Severity and Outcome of COVID-19 Disease in Relation to Age, Male Gender, Diabetes Mellitus, and Cardiac Diseases

Since our multivariate analysis showed worse severity and outcome in patients who are older in age, males, and have DM, and cardiac diseases (Tables 7 and 8), we studied the effect of vaccination status on the severity and outcome of COVID-19 disease in relation to the above comorbidities. We found that unvaccinated patients who were either older in age, males, or had DM or cardiac diseases had severe-critical COVID-19 disease, longer hospitalization, higher risk of ICU admission, mechanical ventilation, and death (P <0.0001) (Table 9).

Table 9 The Effect of Vaccination Status on the Severity and Outcome of COVID-19 Disease in Relation to Age, Male Gender, Diabetes Mellitus, and Cardiac Diseases

Association Between Severity and Outcome of COVID-19 Disease and the Type of Vaccine

A comparison of the impact of vaccination types on the severity and outcome of COVID-19 disease did not show any statistically significant association (Table 10).

Table 10 Association Between Severity and Outcome of COVID-19 Disease and Type of Vaccine

Discussion

This is an observational study of 624 patients from two tertiary care centers in Saudi Arabia’s Eastern Province. It was aimed at assessing the impact of COVID-19 vaccination on the hospitalization rates and outcomes of hospitalized patients with COVID-19 infection. Our study showed the following significant key results: First, 70.4% of hospitalized patients were unvaccinated. Next, the unvaccinated group had higher WBCs, neutrophils, CRP, and D-dimer with a lower lymphocyte count, while the PV group had higher LDH and ferritin levels. In addition, un-vaccination status was a significant predictor of critical COVID-19 disease (OR 2.31; P <0.001), whereas full vaccination was associated with significantly milder COVID-19 disease severity (OR 0.36; P 0.01). Moreover, un-vaccination status was an independent predictor of longer hospitalization OR 3.0 (P <0.001), higher need for ICU admission OR 4.7 (P <0.001), mechanical ventilation OR 3.6 (P <0.001), and death OR 4.8 (P <0.001). Furthermore, full vaccination was linked to a significant reduction in the need for ICU admission. (OR 0.49; P 0.045). Finally, older age and DM were associated with worse severity, while older age, male gender, DM, and cardiac diseases were predictors of the worst outcome of COVID-19 infection.

Our findings are consistent with previous research which showed that unvaccinated patients have a higher risk of hospitalization.16,18,19 We found that 70% of hospitalized patients in our cohort were unvaccinated. Similarly, Tenforde et al found that out of 4513 patients who were hospitalized with COVID-19 infection, 84.2% were unvaccinated.16 In addition, Bahl et al reported that 91.9% of COVID-19 patients who required emergency care or hospitalization were unvaccinated, while only 1.1% were FV patients.19 In addition, a large community-based study from the United Kingdom which looked at patients aged 80 years or older found that vaccination with either one dose of Pfizer or AstraZeneca vaccines provided a reduction in emergency care and hospital admission of 43% and 37%, respectively.18

A comparison of laboratory results data between the three study groups revealed that the unvaccinated group had higher COVID-19 severity markers including WBCs, neutrophils, CRP, and D-dimer with a lower lymphocyte count, while the PV group had higher LDH and ferritin levels. Several reports found that LDH, CRP, D-dimer, and ferritin were correlated with worse severity and outcome of COVID-19 disease.20–22 Our results support the findings of worse severity and outcome in the unvaccinated group or the PV group, as we will discuss further in the paper. Most of the published data about the role of the COVID-19 vaccine on the severity of the disease did not investigate the differences in the laboratory parameters between vaccinated and unvaccinated patients.

We have shown that un-vaccination status increased the odds of critical COVID-19 disease by 2.31 times (P<0.001) while FV patients had a significantly milder COVID-19 severity (OR 0.36; P 0.01). Even though it did not show statistical significance in multivariate analysis, univariate analysis has shown that the majority of patients who received a single dose of the vaccine presented with either severe (40.4%) or critical (34.9%) COVID-19 disease. Our results are in line with the findings reported by Singh et al where individuals with FV had a lower likelihood of having severe disease on initial presentation to the hospital (18.2%) compared to PV (31.8%) and unvaccinated (42.6%) cases (P 0.022).23 Overall, FV patients were found to have a lower likelihood of experiencing severe disease (30.3%) during their illness compared to PV (51.3%) and unvaccinated (54.1%) cases in the same study (P 0.035).23 Similarly, Mhawish et al reported more patients from the non-immunized group to have higher severity categories while fewer non-immunized individuals were in the lower severity categories compared to immunized people.24 In addition, the same study found that at least one dose of immunization was related to a diminished odds of higher severity scale (OR 0.2; P < 0.001).24

The analysis of the outcome in our study has shown that un-vaccination status was an independent predictor of longer hospitalization OR 3.0 (P <0.001). We found that 64.8% of the unvaccinated group had a length of stay of more than 7 days. Singh et al investigated 577 COVID-19 cases that were matched with control cases and reported that the highest median length of stay was in the unvaccinated group of 12 days (P 0.028).23 In addition, Olson et al found that the median length of hospital stay was longer in unvaccinated patients compared to vaccinated patients.25 We also found a higher need for ICU admission OR 4.7 (P <0.001) and mechanical ventilation OR 3.6 (P <0.001) in the unvaccinated group. On the other hand, full vaccination reduced the odds of ICU admission (OR 0.49; P 0.045). Previous reports support our findings, as was reported by Mhwaish et al, where a minority of hospitalized patients in ICU (5 patients out of 611 patients) were FV.24 In our cohort, only 5 FV patients out of 250 were admitted to ICU. On the same line, Olson et al reported that only 2 out of 180 patients who required ICU admission were fully vaccinated.25 Moreover; Moghadas et al reported that COVID-19 vaccination led to a marked reduction of adverse outcomes, including non-ICU hospitalization by 63.5% and ICU hospitalization by 65.6%.26

Interestingly, our analysis showed that un-vaccination status increased the odds of death by 4.8 times (P <0.001). The same study by Mhwaish et al reported that the non-immunized group had a higher death rate (43.9% versus 29.4%; P 0.02).24 Similarly, Tenforde et al found a higher risk of mechanical ventilation or death by day 28 in unvaccinated patients in a study of 1197 hospitalized COVID-19 patients.16 Moreover, an observational study conducted by Haas et al reported a higher mortality rate among unvaccinated patients.27 Additionally, Moghdas et al reported a reduced death rate in vaccinated patients by 69.3%.26 Furthermore, another report found that at least a single dose of immunization lowered the adjusted odds of 30-day all-cause mortality (OR 0.45; P 0.02).24 On the other hand, only one study reported similar outcomes of death and recovery across different groups of vaccinations.23

Our study showed no difference in the severity and outcome of COVID-19 disease between patients who received either Pfizer or AstraZeneca vaccines. Similarly, Bernal et al in a large community-based study reported that either Pfizer or AstraZeneca vaccines were associated with similar protection against symptomatic and severe COVID-19 disease in older adults.18 In addition, Kaura et al found comparable effectiveness of both vaccines against hospitalization and mortality.28

According to our analysis, the presence of older age, male gender, diabetes mellitus, and cardiac diseases were associated with severe/critical COVID-19 infection and poor clinical outcomes as was previously published in the literature.29–33 However, further analysis showed that the majority of patients with those comorbidities who had worse severity and outcome were unvaccinated (Table 9). This signifies the positive protective effect of the COVID-19 vaccine against severe disease and worse outcomes, especially in high-risk group patients.

Our study has shown that the majority of COVID-19 patients who required hospitalization were unvaccinated. In addition, un-vaccination status was an independent predictor of severe to critical COVID-19 disease, while full vaccination lowered the odds of critical COVID-19 infection. Moreover, un-vaccination status increased the odds of longer hospitalization, ICU admission, mechanical ventilation, and death. Therefore, our study confirms the positive impact of the COVID-19 vaccine in reducing the rate of hospital admission, severe to critical COVID-19 pneumonia, and worst outcomes and most importantly, mortality. Meanwhile, un-vaccination increased the risk of the worst outcome in patients with comorbidities. Finally, both types of COVID-19 vaccine that were included in the study had similar protective effects against the worst outcome of COVID-19 infection.

Strengths and Limitations

There are several strong points in our study. First, this is a double center study with an appropriate sample size and rigorous inclusion and exclusion criteria. Second, this is real-world data that was collected to assess and quantify the severity and outcome of COVID-19 infection in vaccinated versus unvaccinated patients admitted with COVID-19 infection. Third, the collected variables were extracted strictly using a particular protocol for minimizing extraction errors and missing values.

However, there are some limitations to this study that should be acknowledged. First, it is a retrospective research with limited generalizability. Second, the temporality from receiving the vaccine to the acquisition of infection was not addressed which would have resulted in a better understanding.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

There is no funding to report.

Disclosure

The authors declared no conflicts of interest in relation to this work.

References

1. Dhar Chowdhury S, Oommen A. Epidemiology of COVID-19. J Dig Endosc. 2020;11(1):03–07. doi:10.1055/s-0040-1712187

2. Office WHOEMR. Updated Clinical Management Guidelines for COVID-19. Vol. 13. Weekly Epidemiology Monitor; 2020.

3. Khandia R, Singhal S, Alqahtani T, et al. Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic. Environ Res. 2022;209:112816. doi:10.1016/j.envres.2022.112816

4. COVID 19 Dashboard: Saudi Arabia. Gov.sa; 2022. Available from: https://covid19.moh.gov.sa/. Accessed June 13, 2022.

5. Reuters Graphics. Saudi Arabia: the latest coronavirus counts, charts and maps. Reuters; 2020. Available from: https://graphics.reuters.com/world-coronavirus-tracker-and-maps/countries-and-territories/saudi-arabia. Accessed June 13, 2022.

6. da Rosa Mesquita R, Francelino Silva Junior LC, Santos SFM, et al. Clinical manifestations of COVID-19 in the general population: systematic review. Wien Klin Wochenschr. 2021;133(7–8):377–382. doi:10.1007/s00508-020-01760-4

7. Saudi MoH protocol for patients suspected of/confirmed with COVID-19 Supportive care and antiviral treatment of suspected or confirmed COVID-19 infection [Internet]; 2022. Available from: https://www.moh.gov.sa/Ministry/MediaCenter/Publications/Documents/MOH-therapeutic-protocol-for-COVID-19.pdf. Accessed June 13, 2022.

8. World Health Organization. Saudi Arabia: WHO Coronavirus disease (COVID-19) dashboard with vaccination data [Internet]; 2022. Available from: https://covid19.who.int/region/emro/country/sa. Accessed June 13, 2022.

9. Ehreth J. The global value of vaccination. Vaccine. 2003;21(7–8):596–600. doi:10.1016/s0264-410x(02)00623-0

10. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162B2 mrna covid-19 vaccine. N Engl J Med. 2020;383(27):2603–2615. doi:10.1056/NEJMoa2034577

11. Sadoff J, Gray G, Vandebosch A, et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against covid-19. N Engl J Med. 2021;384(23):2187–2201. doi:10.1056/NEJMoa2101544

12. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mrna-1273 SARS-COV-2 vaccine. N Engl J Med. 2021;384(5):403–416. doi:10.1056/NEJMoa2035389

13. World Health Organization. COVID-19 vaccines advice. [cited 2022 Feb 4]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines/advice. Accessed June 13, 2022.

14. Saudi Press agency. SFDA approves registration of Pfizer-BioNTech COVID-19 vaccine; 2020. Available from: https://www.spa.gov.sa/viewfullstory.php?lang=en&newsid=2166947. Accessed June 13, 2022.

15. Saudi Food & Drug Authority. Saudi food & drug authority allows the import and use of AstraZeneca covid 19 vaccine; 2021. Available from: https://sfda.gov.sa/en/news/79059. Accessed June 13, 2022.

16. Tenforde MW, Self WH, Adams K, et al. Association between mrna vaccination and COVID-19 hospitalization and disease severity. JAMA. 2021;326(20):2043–2050. doi:10.1001/jama.2021.19499

17. Alwafi H, Naser AY, Qanash S, et al. Predictors of length of hospital stay, mortality, and outcomes among hospitalised COVID-19 patients in Saudi Arabia: a Cross-Sectional Study. J Multidiscip Healthc. 2021;14:839–852. doi:10.2147/JMDH.S304788

18. Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of the pfizer-biontech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study. BMJ. 2021:n1088. doi:10.1136/bmj.n1088

19. Bahl A, Johnson S, Maine G, et al. Vaccination reduces need for emergency care in breakthrough COVID-19 infections: a multicenter cohort study. Lancet Reg Health Am. 2021;4:100065. doi:10.1016/j.lana.2021.100065

20. Henry BM, Aggarwal G, Wong J, et al. Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: a pooled analysis. Am J Emerg Med. 2020;38(9):1722–1726. doi:10.1016/j.ajem.2020.05.073

21. Hussein AM, Taha ZB, Gailan Malek A, et al. D-dimer and serum ferritin as an independent risk factor for severity in COVID-19 patients. Materials Today. 2021. doi:10.1016/j.matpr.2021.04.009

22. Liu F, Li L, Xu MD, et al. Prognostic value of interleukin-6, C-reactive protein, and Procalcitonin in patients with covid-19. J Clin Virol. 2020;127:104370. doi:10.1016/j.jcv.2020.104370

23. Singh C, Naik B, Pandey S, et al. Effectiveness of COVID-19 vaccine in preventing infection and disease severity: a case-control study from an Eastern State of India. Epidemiol Infect. 2021;149:E224. doi:10.1017/S0950268821002247

24. Mhawish H, Mady A, Alaklobi F, et al. Comparison of severity of immunized versus non-immunized COVID-19 patients admitted to ICU: a prospective observational study. Ann Med Surg. 2021;71:102951. doi:10.1016/j.amsu.2021.102951

25. Olson SM, Newhams MM, Halasa NB, et al. Effectiveness of BNT162B2 vaccine against critical covid-19 in adolescents. N Engl J Med. 2022;386(8):713–723. doi:10.1056/nejmoa2117995

26. Moghadas SM, Vilches TN, Zhang K, et al. The impact of vaccination on coronavirus disease 2019 (COVID-19) outbreaks in the United States. Clin Infect Dis. 2021;73(12):2257–2264. doi:10.1093/cid/ciab079

27. Haas EJ, Angulo FJ, McLaughlin JM, et al. Impact and effectiveness of mrna BNT162b2 vaccine against SARS-COV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using National Surveillance Data. Lancet. 2021;397(10287):1819–1829. doi:10.1016/s0140-6736(21)00947-8

28. Kaura A, Trickey A, Shah AS, et al. Comparing the longer-term effectiveness of a single dose of the pfizer-biontech and Oxford-AstraZeneca covid-19 vaccines across the age spectrum. eClinicalMedicine. 2022;46:101344. doi:10.1016/j.eclinm.2022.101344

29. Huang I, Lim MA, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in covid-19 pneumonia – a systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2020;14(4):395–403. doi:10.1016/j.dsx.2020.04.018

30. Xu J, Xiao W, Liang X, et al. A meta-analysis on the risk factors adjusted association between cardiovascular disease and covid-19 severity. BMC Public Health. 2021;21(1). doi:10.1186/s12889-021-11051-w

31. Statsenko Y, Al Zahmi F, Habuza T, et al. Impact of age and sex on covid-19 severity assessed from radiologic and clinical findings. Frontiers. 2022;2022:1395. doi:10.3389/fcimb.2021.777070

32. Marik PE, DePerrior SE, Ahmad Q, Dodani S. Gender‐based disparities in COVID-19 patient outcomes. J Investig Med. 2021;69(4):814–818. doi:10.1136/jim-2020-001641

33. Livanos AE, Jha D, Cossarini F, et al. Gastrointestinal involvement attenuates COVID-19 severity and mortality. MedRxiv. 2020. doi:10.1101/2020.09.07.20187666

34. Coronavirus disease (covid-19): Vaccines. World Health Organization; 2022. Available from: https://www.who.int/news-room/questions-and-answers/item/coronavirus-disease-covid-19-vaccines?gclid=Cj0KCQjwmuiTBhDoARIsAPiv6L91ecmYWZ16a2_QXNynlgUKnClcrua0JQ38PywMl763wN1n85tGGAcaApfuEALw_wcB&topicsurvey=v8kj13. Accessed June 13, 2022.

35. Loo KY, Letchumanan V, Ser HL, et al. Covid-19: insights into potential vaccines. Microorganisms. 2021;9(3):605. doi:10.3390/microorganisms9030605

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