Abstract
The clinical guideline states that COVID-19 vaccination can be administered concurrently with Influenza (flu) vaccination (dual vaccination). Using data from the 2021 National Health Interview Survey, we conducted descriptive analysis and multivariate logistic regressions to examine the association between dual vaccination status and self-reported COVID-19 infection and severity. Among 21,387 (weighted 185,251,310) U.S. adults, about 22% did not receive either the flu or COVID-19 vaccine, 6.0% received the flu vaccine only, 29.1% received the COVID-19 vaccine only, and 42.5% received both vaccines. In the multivariate analysis, individuals with dual vaccination (OR, 0.65, 95% CI, 0.56–0.75) and COVID-19 vaccine only (OR, 0.71, 95% CI, 0.61–0.82) were significantly less likely to report COVID-19 infection when compared with those unvaccinated. There was no significant difference in self-reported COVID-19 symptom severity by vaccination status. The results suggest that dual vaccination may be an effective strategy to reduce the contagious respiratory disease burden.
Keywords: COVID-19, Influenza, Dual vaccination
1. Introduction
Although the vaccines developed for COVID-19 had decreased hospitalization and death as the endpoints, some data suggests that the COVID-19 vaccines may decrease the likelihood of infection and even reinfection after natural infection [1], [2]. There is some indication of a cross-variant neutralizing response to the COVID-19 vaccine. The results are mixed, however some studies suggested that influenza vaccination may attenuate the impact of COVID-19 potentially through a vaccine-induced change in innate immunity and a cross-reactivity response [3], [4], [5], [6].
The current clinical guideline suggests that COVID-19 vaccination can be administered concurrently with a seasonal flu vaccination [7]. Despite this, there is widespread vaccination mistrust and hesitancy among the general public [8], [9] and an ongoing debate about whether it is effective or safe to get COVID-19 and flu vaccines simultaneously (hereafter, dual vaccination) [10], [11]. It has been discovered that dual vaccination does not pose any safety concerns based on clinical trials [12]. However, an earlier study has reported that dual vaccination was associated with significant increases in self-reported adverse reactions (such as fatigue, headaches, and myalgia) compared with flu vaccines or COVID-19 boosters alone [13]. A dual vaccination that protects against COVID-19 and seasonal flu may benefit the population and the healthcare system (i.e., reducing healthcare spending on care for COVID-19 or flu). However, there is a lack of population-based evidence to help better communicate the effectiveness or potential harms associated with dual vaccination and inform decisions about practice and policy. To address this, we used recent national data to examine the association between dual vaccination status and COVID-19 infection and symptom severity.
2. Methods
We performed secondary analyses using the 2021 National Health Interview Survey (NHIS) data [14]. The 2021 NHIS asked about positive COVID-19 diagnoses among participants aged 18 years or older who tested for COVID-19 and collected vaccination data from April 2021 to December 2021 in the U.S. For those who tested, it further asked about coronavirus symptoms. We operationalized the vaccination status as unvaccinated, flu shot only, COVID-19 vaccine only, and dual vaccination.
Data were analyzed using SAS 9.4 (SAS Institute, Cary, NC). First, descriptive statistics and chi-square tests were utilized to compare the respondents' characteristics by their vaccination status. Second, the weight-adjusted prevalence of COVID-19 infection was calculated for the four groups of vaccination statuses. Third, the association between vaccination status and COVID-19 infections using simple and multivariate-adjusted logistic regression models was estimated, the latter adjusted for age, sex, race/ethnicity, marital status, education attainment, family federal poverty level, insurance coverage, census region, urban/rural, usual source of care, health status, number of chronic conditions, and interview month. Finally, based on the survey questions: “How would you describe your coronavirus symptoms when they were at their worst? Would you say no symptoms, mild symptoms, moderate symptoms, or severe symptoms?” sub-group analyses to test the relationship between vaccination status and the presence of self-reported severity of COVID-19 symptoms (no, mild, moderate, severe) among adults who were diagnosed with COVID-19 were conducted. Statistical significance was set at a p-value < 0.05 (2-tailed). This study was deemed exempt from review by the Institutional Board of the University of Florida.
3. Results
Our final unweighted sample included 21,387 individuals aged 18 years or older, representing 185,251,310 noninstitutionalized adults in the U.S. Using the weighted sample, 14.4 % (26,706,881) had a history of COVID-19 infection. 22.4 % (41,525,989) did not receive either flu or COVID-19 vaccine, 6.0 % (11,048,096) had flu-shots only, 29.1 % (53,999,982) received COVID-19 vaccine only, and 42.5 % (78,677,242) had both the flu and COVID-19 vaccine.
Table 1 shows the descriptive statistics of the study sample and bivariate analysis based on the vaccination status. Compared to unvaccinated respondents, a higher percentage of respondents who received both flu and COVID-19 vaccines were aged ≥ 65 years, were female, were non-Hispanic White, were married, had higher education and higher income, covered by health insurance, resided in the Northeast region and large central metro area, had a usual source of care, reported fair/poor health status, and had ≥ 2 chronic conditions (all p < 0.05).
Table 1.
Respondents’ Sociodemographic and Health-Related Characteristics by Vaccination Status.
| Vaccination Status |
|||||
|---|---|---|---|---|---|
| Characteristic | Unvaccinated No. (%) |
Flu shot only No. (%) |
Covid-19 Vaccine only No. (%) | Dual vaccines No. (%) |
P-value |
| Covid-19 Diagnosis | <0.001 | ||||
| No | 33705527(81.2) | 8,698,317 (78.7) | 46,454,011 (86.0) | 69,686,574 (88.6) | |
| Yes | 7,820,463 (18.8) | 2,349,779 (21.3) | 7,545,970 (14.0) | 8,990,669 (11.4) | |
| Age Group | <0.001 | ||||
| 18–49 | 30,684,857 (73.9) | 6,675,635 (60.4) | 31,544,438 (58.4) | 29,742,931 (37.8) | |
| 50–64 | 7,462,171 (18.0) | 2,526,802 (22.9) | 14,371,774 (26.6) | 21,089,987 (26.8) | |
| ≥65 | 3,378,961 (8.1) | 1,845,659 (16.7) | 8,083,770 (15.0) | 27,844,324 (35.4) | |
| Sex | <0.001 | ||||
| Male | 21,762,924 (52.4) | 4,472,587 (40.5) | 28,181,012 (52.2) | 35,117,475 (44.6) | |
| Female | 19,763,065 (47.6) | 6,575,509 (59.5) | 25,818,970 (47.8) | 43,559,767 (55.4) | |
| Race/Ethnicity | <0.001 | ||||
| N on-Hispanic White | 24,573,080 (59.2) | 7,029,354 (63.6) | 30,627,066 (56.7) | 54,413,004 (69.1) | |
| Non-Hispanic Black | 6,022,225 (14.5) | 1,450,397 (13.1) | 7,117,216 (13.2) | 6,827,135 (8.7) | |
| Hispanic | 8,626,489 (20.8) | 1,932,116 (17.5) | 10,982,721 (20.3) | 9,885,593 (12.6) | |
| Other | 2,304,196 (5.5) | 636,229 (5.8) | 5,272,977 (9.8) | 7,551,510 (9.6) | |
| Marital Status | <0.001 | ||||
| Married | 16,708,146 (40.2) | 5,027,079 (45.5) | 26,306,229 (48.7) | 46,681,029 (59.3) | |
| Single | 18,445,055 (44.4) | 4,590,219 (41.5) | 21,918,936 (40.6) | 26,822,692 (34.1) | |
| Other | 6,372,789 (15.3) | 1,430,798 (13.0) | 5,774,817 (10.7) | 5,173,522 (6.6) | |
| Education Attainment | <0.001 | ||||
| Some high school or less | 7,471,022 (18.0) | 2,190,494 (19.8) | 5,871,679 (10.9) | 7,370,521 (9.4) | |
| High school graduate | 15,057,433 (36.3) | 3,391,155 (30.7) | 13,451,659 (24.9) | 15,833,532 (20.1) | |
| Some college/associate degree | 11,827,852 (28.5) | 3,227,496 (29.2) | 14,522,922 (26.9) | 18,786,079 (23.9) | |
| College graduate | 7,169,682 (17.3) | 2,238,952 (20.3) | 20,153,721 (37.3) | 36,687,110 (46.6) | |
| Family Federal Poverty Level | <0.001 | ||||
| >400 % | 11,760,454 (28.3) | 3,305,122 (29.9) | 23,461,498 (43.4) | 42,407,832 (53.9) | |
| 200 %-400 % | 13,105,724 (31.6) | 3,264,668 (29.5) | 16,414,966 (30.4) | 21,094,013 (26.8) | |
| <200 % | 16,659,812 (40.1) | 4,478,306 (40.5) | 14,123,517 (26.2) | 15,175,397 (19.3) | |
| Insurance Coverage | <0.001 | ||||
| Yes | 33,037,675 (79.6) | 9,753,721 (88.3) | 47,431,548 (87.8) | 76,317,801 (97.0) | |
| No | 8,488,314 (20.4) | 1,294,376 (11.7) | 6,568,433 (12.2) | 2,359,442 (3.0) | |
| Census Region | <0.001 | ||||
| Northeast | 5,243,335 (12.6) | 1,663,364 (15.1) | 9,782,959 (18.1) | 15,533,217 (19.7) | |
| Midwest | 8,744,698 (21.1) | 2,443,629 (22.1) | 10,373,994 (19.2) | 17,140,393 (21.8) | |
| South | 18,716,655 (45.1) | 4,671,996 (42.3) | 19,892,738 (36.8) | 26,896,580 (34.2) | |
| West | 8,821,301 (21.2) | 2,269,108 (20.5) | 13,950,290 (25.8) | 19,107,052 (24.3) | |
| Urban/Rural | <0.001 | ||||
| Large central metro | 11,419,348 (27.5) | 2,810,664 (25.4) | 19,533,963 (36.2) | 25,068,683 (31.9) | |
| Large fringe metro | 8,610,995 (20.7) | 2,402,404 (21.7) | 13,447,566 (24.9) | 20,225,741 (25.7) | |
| Medium/small metro | 14,090,709 (33.9) | 3,709,887 (33.6) | 15,409,063 (28.5) | 23,765,562 (30.2) | |
| Nonmetropolitan | 7,404,937 (19.2) | 2,125,141 (19.2) | 5,609,390 (10.4) | 9,617,257 (12.2) | |
| Usual Source of Care | <0.001 | ||||
| Yes | 33,462,491 (80.6) | 10,173,141 (92.1) | 47,066,221 (87.2) | 75,626,415 (96.1) | |
| No | 8,063,499 (19.4) | 874,955 (7.9) | 6,933,761 (12.8) | 3,050,827 (3.9) | |
| Health Status | <0.001 | ||||
| Excellent | 11,840,268 (28.5) | 2,426,534 (22.0) | 13,796,768 (25.5) | 17,257,723 (21.9) | |
| Very good | 13,713,820 (33.0) | 3,513,669 (31.8) | 18,620,304 (34.5) | 27,536,622 (35.0) | |
| Good | 10,920,882 (26.3) | 3,028,655 (27.4) | 14,957,823 (27.7) | 22,680,761 (28.8) | |
| Fair/poor | 5,051,019 (12.2) | 2,079,238 (18.8) | 6,625,086 (12.3) | 11,202,137 (14.2) | |
| Number of Chronic Condition | <0.001 | ||||
| 0 | 27,341,136 (65.8) | 5,528,192 (50.0) | 32,469,587 (60.1) | 35,855,221 (45.6) | |
| 1 | 9,962,779 (24.0) | 3,480,958 (31.5) | 14,656,036 (27.1) | 25,127,660 (31.9) | |
| ≥2 | 4,222,075 (10.2) | 2,038,947 (18.5) | 6,874,359 (12.7) | 17,694,362 (22.5) | |
| Interview Time | <0.001 | ||||
| Quarter 2 | 17,995,485 (43.3) | 5,993,244 (54.2) | 13,693,943 (25.4) | 24,098,524 (30.6) | |
| Quarter 3 | 12,537,406 (30.2) | 3,108,341 (28.1) | 18,150,344 (33.6) | 27,844,153 (35.4) | |
| Quarter 4 | 10,993,099 (26.5) | 1,946,512 (17.6) | 22,155,694 (41.0) | 26,734,565 (34.0) | |
Table 2 presents the association between COVID-19 infection with vaccination status. Respondents with dual vaccination history had the lowest COVID-19 infection rate (11.4 %, 95% CI, 10.6 %-12.2 %). The multivariate-adjusted regression model showed that people with COVID-19 vaccine only (OR, 0.71, 95% CI, 0.61–0.82) and dual vaccination (OR, 0.65, 95% CI, 0.56–0.75) were significantly less likely to report a COVID-19 infection compared to unvaccinated people. However, there were no significant differences between COVID-19 vaccine only and dual vaccines in the likelihood of COVID-19 infection in the multivariate regression model (data not shown).
Table 2.
Association of COVID-19 Infection with Vaccination Status.
| Vaccination Status | COVID-19 infection Prevalence % (95 % CI) |
Unadjusted Odds Ratio (95 % CI) |
Adjusted Odds Ratio* (95 % CI) |
|---|---|---|---|
| Unvaccinated | 18.8 (17.3–20.4) | 1.00 (reference) | 1.00 (reference) |
| Flu shot only | 21.3 (18.2–24.4) | 1.16 (0.94–1.44) | 1.23 (0.99–1.54) |
| Covid-19 only | 14.0 (12.9–15.1) | 0.70 (0.61–0.80) | 0.71 (0.61–0.82) |
| Dual vaccines | 11.4 (10.6–12.2) | 0.56 (0.49–0.63) | 0.65 (0.56–0.75) |
*adjusting for age, sex, race/ethnicity, marital status, education attainment, family federal poverty level, census region, urban/rural, insurance coverage, usual source of care, health status, number of chronic conditions, and time of interview.
Among those diagnosed with COVID-19, 8.0 % had no symptoms, 35.8 % reported mild symptoms, 36.7 % reported moderate, and 19.6 % had severe symptoms. About two-thirds lost some or all of their sense of smell, and 59.4 % lost their sense of taste. There were no significant differences in the overall severity of symptoms or loss of taste across people with different vaccination statuses (all p > 0.05; data not shown).
4. Discussion
Using nationally representative data, we found that US adults who received the COVID-19 vaccine only or dual vaccination (both COVID-19 and flu) were significantly less likely to report COVID-19 infection compared with those unvaccinated. However, we did not find significant differences in the severity of symptoms among those who with COVID-19 infection by different vaccination statuses. Although dual vaccination seems to have a lower likelihood of COVID-19 infection in general, we would like to emphasize that COVID-19 vaccines are intended to prevent and reduce illness severity caused by COVID-19, not the flu vaccine.
Earlier studies found the uptake of flu vaccination was associated with lower hospitalization and deaths from COVID-19 among the elderly [3], [15], [16], [17]. However, the current study did not find a significant association between the flu vaccine alone and COVID-19 infection in the general population. This finding is consistent with previous studies with null findings on flu vaccination and COVID-19/non-influenza infections at the population level, [18], [19] suggesting no interference in immunological mechanisms between flu vaccines and COVID-19 infection from an epidemiological perspective.
In the 2021–2022 flu season, influenza incidence was significantly lower than pre-pandemic levels, this might have been related to society's widespread adoption of COVID-19-related mitigation measures like hand washing and mask-wearing [19]. However, the country may face severe challenges in the 2022–2023 flu season due to the simultaneous circulating influenza virus and virus that causes COVID-19 while loosening protection measures and the reduced population immunity (an early increase in influenza activity has been reported) [20]. According to a recent study, public acceptance of vaccination is below 50 % for a COVID-19 booster alone, 58 % for influenza alone, and 50 % for both [21]. Given the effective protections from the current COVID-19 booster and flu vaccine, we should strive to send clear messages to the public that dual vaccination is an efficient and safe strategy in the flu season with simultaneous circulating SARS-CoV-2. These health messages should provide information and evidence on how vaccines protect vulnerable populations, such as the elderly or those with complex comorbidities who are disproportionately susceptible to respiratory infections [21], [22]. Focusing educational campaigns on the benefits of dual vaccinations and patient-related cost-saving may help improve vaccination rates [23], [24].
5. Limitations
Study limitations include self-reported COVID-19 and vaccine-related information may be subject to recall and social-desirability bias. Moreover, the misclassification of COVID-19 infection status due to the asymptomatic infection may underestimate the associations between vaccination status and COIVD-19 infection [25]. Lastly, the efficacy of COVID-19 vaccines varied by the virus variants, [26] lack of variant information may affect the study findings. However, adjusting for interview month in the multivariate models mitigated these impacts.
6. Conclusions
The study findings suggest that dual vaccinations are associated with reduced COVID-19 infection than unvaccinated individuals. Dual and COVID-19-only vaccinations seem to have comparable associations with COVID-19 infection. Given potential winter surge, dual vaccination may be an effective strategy to reduce the contagious respiratory disease burden.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
Zhigang Xie had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Young-Rock Hong, Zhigang Xie, and Arch G. Mainous III contributed to the study conception and design; Zhigang Xie and Young-Rock Hong contributed to statistical analysis; all authors contributed to the acquisition, analysis, or interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content.
Data availability
The National Health Interview Survey (NHIS) data that support the findings of this study are publicly available at https://www.cdc.gov/nchs/nhis/data-questionnaires-documentation.htm.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The National Health Interview Survey (NHIS) data that support the findings of this study are publicly available at https://www.cdc.gov/nchs/nhis/data-questionnaires-documentation.htm.