Influenza Vaccine and COVID-19 Pandemic: Could This Vaccine Help Limit the Potential Adverse Consequences of SARS-CoV-2?

authors:

avatar Reza Mosaed 1 , avatar Hossein Fasihi 2 , avatar Amir Norouzi 3 , avatar Vahid Anjomanian 3 , avatar Mohammad Afshar Ardalan 4 , avatar Farshid Alazmani Noodeh 5 , avatar Ali Reza Khoshdel 6 , *

Department of Clinical Pharmacy, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
Biomaterial and Medicinal Chemistry Research Center, AJA University of Medical Sciences, Tehran, Iran
Iran Armed Forces Health Insurance Organization, Tehran, Iran
Internal Medicine Department, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
Critical Care Nursing Department, Faculty of Nursing, Aja University of Medical Sciences, Tehran, Iran
Department of Public Health, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

how to cite: Mosaed R, Fasihi H, Norouzi A, Anjomanian V, Ardalan M A, et al. Influenza Vaccine and COVID-19 Pandemic: Could This Vaccine Help Limit the Potential Adverse Consequences of SARS-CoV-2?. Iran J Pharm Res. 2022;In Press(In Press):e127032. doi: 10.5812/ijpr-127032.

Abstract

The COVID-19 pandemic has prompted researchers to find treatments and vaccines to control SARS-CoV-2. There are some hypotheses about the benefit of respiratory virus vaccines, like MMR, for COVID-19 pneumonia severity, morbidity, and mortality. The influenza vaccine is one of the most frequently used respiratory virus vaccines covered by one of the Iranian insurance institutes. We have a symmetrical group of participants that have received this vaccine that could be compared with each other. We compared 3,379 persons aged 20 - 75 years for the effect of the influenza vaccine on COVID-19 mortality. We ultimately found that it does not affect mortality caused by COVID-19 pneumonia, but it can decrease the hospitalization cost in people over 65 years with a history of chronic disease.

1. Background

A novel coronavirus named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), first reported in December 2019, has spread worldwide (1). Almost five million deaths have been reported from over 250 million positive cases by November 6, 2021. Coronaviruses (CoVs) mainly spread through respiratory droplets released from the saliva and mucus secretions from the mouth and nose during coughing, laughing, talking, breathing, sneezing, and singing (2). These virus droplets may have access to the body mainly via the nose, mouth, and eyes but not via the intact skin (3). Although SARS-CoV-2 is less lethal than the two earlier coronaviruses, SARS and MERS, it is more contagious (4).

The COVID-19 deaths are primarily attributed to respiratory failure caused by the cytokine storm, possibly due to the over-stimulation of the immune system (5). Many patients who die from SARS-CoV-2 respiratory infection have had concomitant infections or comorbidities (6). There is no effective and approved treatment for this respiratory infection. Prevention of other respiratory pathogen infections would help decrease COVID-19 infection mortality (7, 8).

Various COVID-19 resistance rates have been reported among different age groups. Infection rates were lower among children than among adults and elders. Though the mechanism for different severities and infection susceptibilities is unknown, this could be due to different quantities and qualities of the immune efficiency due to recent or previous vaccinations and infections.

2. Objectives

It appears that people in geographical locations with a high MMR vaccination rate have a lower COVID-19 death rate (9). There is also evidence that 955 sailors from the USS Roosevelt tested positive for the Coronavirus. The sailors exhibited milder symptoms, which may have been because all US Navy recruits must receive the MMR vaccine (10). Similarly, influenza vaccination may play a role in decreasing SARS-CoV-2 infection mortality. Our study tests this hypothesis.

3. Methods

The study population consisted of all insured individuals by one of the basic national health insurance organizations of the Islamic Republic of Iran, which covers flu vaccine administration for the insured according to eligibility criteria. This prospective study was conducted between August 2020 and February 2020. First, information about the people covered by this organization was extracted from relevant and reputable databases. In total, 21,071 persons aged 20 - 75 years were randomly selected from the list of insured persons covered by the mentioned insurance organization. Among them, 19,293 persons formed the study sample. Via three phases of short message service (SMS) notification, all of the individuals were asked to answer the questions by referring to the electronic portal of the insurance organization. During 30 days of the data collection phase, 3,435 persons referred to the announced electronic portal and completed the questionnaire. The accuracy of the answers was checked by calling the respondents. Therefore, individuals were divided into two general groups in this study: Vaccinated and non-vaccinated. This research utilized a researcher-made questionnaire of multiple-choice questions.

The questionnaires were reviewed and refined. Extra information on demographic data and costs of 3,379 people were also extracted from the organization’s databases, including gender, age, geographical area of residence, the total number of visits to medical centers, the total cost of treatment, frequency of inpatient services use, and the total cost of inpatient services during the study period.

4. Results

In this study, 1,172 people who had been vaccinated against the flu were compared with 2,207 people who had not been vaccinated. The two groups were matched for age and gender. However, the vaccinated people were older on average and had more frequent comorbidities (Table 1).

Table 1. Specifications of Vaccinated and Non-vaccinated Groups a
VariablesVaccinated (N = 1172)Non-vaccinated (N = 2207)P-Value
Age (mean ± SD)58.2 ± 9.857.1 ± 10.70.004
Male gender1082 (92.3)1910 (86.5)0.0001
Diabetes385 (32.8)578 (26.2)0.0001
CV events history374 (31.9)461 (20.9)0.0001
Hypertension434 (37.0)608 (27.5)0.0001
Malignancies53 (4.5)48 (2.2)0.0001
Organ transplantation30 (2.6)18 (0.8)0.0001
Immunosuppressive therapy127 (10.8)113 (5.1)0.0001
Current chemotherapy48 (4.1)41 (1.9)0.0001
Asthma67 (5.7)55 (2.5)0.0001
COPD53 (4.5)25 (1.1)0.0001
Chemical gas exposure439 (37.5)493 (22.3)0.0001
Morbid obesity42 (3.6)63 (2.9)0.24

Comparing the two groups in terms of COVID-19 diagnosis and mortality rates did not show any statistically significant difference (Table 2).

Table 2. Comparison of Outcomes in Vaccinated and Non-vaccinated Groups a
VariablesVaccinated (N = 1172)Non-vaccinated (N = 2207)P-Value
Mortality7 (0.6)17 (0.8)0.67
COVID-19 diagnosis51 (4.5)82 (3.8)0.35

A comparison of the dead and living groups showed that studied population were older and, unexpectedly, the percentage of females was higher in the dead group. People with malignancy treated with immunosuppressants and chemotherapy, asthma, and chronic respiratory disease were more likely to die. There were fewer cases in the group of dead people with a history of exposure to chemical gases (Table 3).

Table 3. Analysis of Variables in Dead and Living Groups a
VariablesDead (N = 24)Living (N = 3354)P-Value
Age (mean ± SD)62.9 ± 15.857.4 ± 10.40.01
Male gender17 (70.8)2974 (88.7)0.01
Diabetes8 (33.3)955 (23.5)0.65
CV events history7 (29.2)827 (24.7)0.61
Hypertension7 (29.2)1034 (30.8)0.86
Malignancies2 (8.3)99 (3.0)0.12
Organ transplantation048 (1.4)-
Immunosuppressive therapy4 (16.7)236 (7.0)0.07
Current chemotherapy2 (8.3)87 (2.6)0.08
Asthma3 (12.5)119 (3.5)0.05
COPD2 (8.3)76 (2.3)0.05
Chemical gas exposure2 (8.3)930 (27.7)0.03
Morbid obesity1 (4.2)104 (3.1)0.76
Recent influenza vaccination7 (29.2)1164 (34.7)0.67
COVID-19 diagnosis2 (8.3)131 (3.9)0.43

In terms of COVID-19 infection, the history of chronic respiratory diseases, in particular asthma, history of exposure to chemical gases, and history of cardiovascular diseases were significantly correlated to the greater risk of COVID-19 infection, as noted in Table 4. Diabetes was marginally higher in the infected group.

Table 4. Analysis of Univariate Factors Associated With COVID-19 a
VariablesCOVID-19 diagnosis (N = 133)No COVID-19 diagnosis (N = 3180)P-Value
Age (mean ± SD)57.5 ± 10.457.5 ± 10.80.95
Male gender115 (86.5)2820 (88.7)0.43
Diabetes47 (35.3)902 (28.4)0.08
CV events history43 (32.3)775 (24.4)0.04
Hypertension44 (33.1)987 (31.0)0.62
Malignancies2 (1.5)98 (3.1)0.30
Organ transplantation2 (1.5)44 (1.4)0.91
Immunosuppressive therapy13 (9.8)221 (6.9)0.21
Current chemotherapy5 (3.8)84 (2.6)0.43
Asthma10 (7.5)108 (3.4)0.01
COPD6 (4.5)70 (2.2)0.08
Chemical gas exposure62 (46.6)846 (26.6)0.0001
Morbid obesity4 (3.0)100 (3.1)0.93
Recent influenza vaccination51 (38.3)1094 (34.4)0.35

More extensive analyses demonstrated that a history of cardiovascular disease increased the risk of COVID-19 infection by about 1.5 times [OR = 1.48 (1.02 - 2.15), P = 0.04]. A history of diabetes also increased the COVID-19 infection by 40% [OR = 1.38 (0.96 - 1.99), P = 0.08]. Also, a history of bronchiectasis and COPD increased the risk of COVID-19 by 2.9 and 2.1 times, respectively. A separate analysis of vaccinated and non-vaccinated groups did not yield new results.

An analysis was done separately in groups with and without underlying chronic disease. Out of 1,476 people who did not have a chronic disease, 47 (3.2%) had COVID-19, while it was 86 out of 1787 (4.5%) in people who had at least one chronic disease (P = 0.02). Multivariate analysis showed that only gender and age had independent effects on mortality, and interestingly, women were more likely to die. A history of influenza vaccine showed no impact on mortality.

Table 5. Multivariate Analysis
VariablesBS.E.WalddfSig.Exp(B)
Gender Code0.9620.4814.00110.0452.618
Age-0.0450.0205.09210.0240.956
COVID-190.0300.6140.00210.9611.030
Diabetes-0.1510.4770.10010.7520.860
CV events history0.0150.2530.00310.9531.015
Hypertension0.1390.1700.67210.4121.149
Malignancies-0.1040.2260.21210.6450.901
Immunosuppressive therapy-0.1740.1222.03110.1540.840
Morbid obesity-0.0250.1580.02610.8720.975
Current chemotherapy-0.0930.1140.66010.4160.911
Asthma-10.1300.6972.62910.1050.323
COPD-0.4410.4570.93210.3340.643
Bronchiectasis-0.0660.2380.07610.7820.936
Recent influenza vaccination0.4720.4810.9 6510.3261.604
Constant5.4221.8848.28010.004226.222

Multivariate analysis of factors affecting COVID-19 showed that these factors did not significantly impact the disease, except for chronic respiratory diseases, which showed a partially independent effect.

Table 6. Multivariate Analysis of Factors Affecting COVID 19
VariablesBS.E.WalddfSig.Exp(B)
Gender Code-0.2360.2640.80010.3710.790
Age-0.0030.0090.09310.7610.997
Diabetes0.2740.1991.89510.1691.315
CV events history0.1570.1032.30310.1291.170
Hypertension-0.0320.0690.21010.6470.969
Malignancies-0.2720.1902.03910.1530.762
Immunosuppressive therapy0.0480.0630.58510.4441.049
Morbid obesity-0.0400.0760.27910.5980.961
Current chemotherapy0.0650.0641.05410.3051.067
Asthma0.6510.3723.06810.0801.918
COPD0.1090.2470.19410.6591.115
Bronchiectasis0.1390.1051.74310.1871.149
Recent influenza vaccination0.0760.1890.16010.6891.079
Constant-2.889.74415.09410.0000.056

Analysis of factors affecting health costs showed that total costs were higher in the vaccinated group because these people were at high risk, were older, and needed greater demands. However, hospitalization and imaging costs were non-significantly lower in the vaccinated group.

Table 7. Analysis of Factors Affecting Health Costs
Variables and History of Influenza VaccinationNMeanStd. DeviationStd. Error MeanP-Value
Hospitalization cost (2018) (IRR)0.65
No39963018760.9586640905.3704337470.499
Yes26659963221.6585304220.9305230337.368
Radiography cost (2018) (IRR)0.59
No13763382072.7118886186.190509137.458
Yes8332977903.7013162817.280456064.588
Visit cost (2018) (IRR) 0.000
No21072795952.342587397.13756367.766
Yes11463920477.523094557.97291412.653
Drug cost (2018) (IRR)0.000
No210912990007.8539511805.730860376.596
Yes116018511311.8030730340.820902273.874
Test cost (2018) (IRR)0.000
No16742688451.363433791.62183925.939
Yes10063323310.683814911.935120277.814
Total cost (2018) (IRR)0.000
No215237354303.4876796865.4401655473.986
Yes116047597349.7568692286.0502016874.965
Hospitalization cost (2019) (IRR)0.57
No40973205548.95103935971.8005139303.045
Yes25968820241.4485692080.7105324646.814
Radiography cost (2019) (IRR)0.92
No13763653143.9217321328.270466951.716
Yes8223579883.4413020608.450454145.871
Visit cost (2019) (IRR)0.000
No16213053668.893601901.95189462.366
Yes9743600435.673492060.379111892.832
Drug cost (2019) (IRR)0.000
No21093105911.543014019.96665630.821
Yes11514392823.413735317.527110100.645
Test cost (2019) (IRR)0.000
No213117022517.7745322908.140981806.818
Yes116523054263.1043907170.0201286389.491
Total cost (2019) (IRR)0.001
No216744843601.7292737312.8301992163.835
Yes116656165027.2783170966.8502435692.590

A separate analysis of hospitalization and imaging costs (type 1 cost) and the costs of visits, tests, and drugs (type 2 cost) in the group with a history of special disease showed the following results in Table 8.

Table 8. Comparison of Cost of Vaccinated and Non-vaccinated Groups
VariablesVaccinatedNon-vaccinatedP-Value
Type 1 cost for disease group (IRR)78’953’94799’928’2420.08
Type 2 cost in disease group (IRR)36’972’76231’558’2060.01
Type 1 cost in disease-free group (IRR)70’946’48465’529’5600.69
Type 2 cost in disease-free group (IRR)25’822’05521’886’5010.40

In other words, influenza vaccination in people with a history of at least one chronic disease significantly reduced the costs of hospitalization and radiology by 110 million Rials per patient per year. However, it increased the outpatient costs by an average of five million Tomans per patient per year. Altogether, vaccination would save 60 million Rials per patient per year.

5. Discussion

Contrary to current information on sex differences in COVID-19 hospitalization and mortality, the percentage of female mortality was higher in our study, possibly because of men's health status (11). Mortality and morbidity from COVID-19 are higher among cancer patients because of the clinical challenges of cancer management, including immunosuppression, aging, and comorbidities (12). This agrees with our report and national studies in the UK (13) and Sweden (14). Asthma and chronic respiratory disease are associated with a risk of severe disease and mortality in COVID-19 infection.

Contrary to expectations, a history of exposure to chemical gases had the opposite effect on mortality. Several reasons can explain this. First, these people in the country are under the constant support of treatment and examination throughout their lives and are treated with the slightest change in their condition. Second, these fragile individuals may have been more careful and taken more stringent preventive measures, as previously reported (15). Third, general quarantine applied for most of the study period resulted in a significant reduction in air pollution (16), which is known to promote the exacerbation of lung disease (17), including COVID-19 exacerbation (18).

A further examination showed that a history of cardiovascular disease increased the risk of COVID-19 infection by 1.5 times because of the COVID-19 effect on the cardiovascular system, which increased the risk of cardiovascular events (19).

5.1. Conclusion

A history of influenza vaccine showed no effect on mortality caused by COVID-19 pneumonia. However, it decreased hospitalization costs in people over 65 years with a history of at least one chronic disease.

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