The status and influencing factors of COVID-19 vaccination in patients with COPD (2024)

Participants

A random survey on the status, influencing factors, and attitudes toward COVID-19 vaccination was conducted using an investigation platform named Wenjuanxing in patients with COPD, focusing on Shengjing Hospital of China Medical University. The questionnaire-based survey was conducted between August 26 and December 27, 2022.

Patients with COPD were recruited throughout the country. The inclusion criteria for the study were as follows: (1) patients diagnosed with COPD, (2) patients who agreed to participate in the study, and (3) patients who provided complete and correct questionnaire information. The exclusion criteria were as follows: (1) patients who had not been diagnosed with COPD, (2) refusal to participate in this study, and (3) incorrect or omitted questionnaire information. Patients underwent spirometry before being included in the study, and questionnaires were administered after the diagnosis of COPD.

COPD was diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2022 guidelines¹³. All COPD patients had definite airflow limitation with a forced expiratory volume in 1s (FEV1)/forceful lung volume (FVC) of < 0.7 after bronchodilator application. Each patient was recruited once and voluntarily agreed to participate. The study was approved by the Ethics Committee of Shengjing Hospital of China Medical University (No. 2022PS1182K), and informed consent was obtained from each participant before administering the questionnaire. All methods were performed in accordance with relevant guidelines and regulations.

Questionnaire design

The questionnaire “Status of COVID-19 vaccination in patients with COPD” was designed with reference to the literature^14,15,16, and in consultation with the relevant experts. The expert panel comprised six experts in the fields of vaccination, infectious diseases, respiratory diseases, and public health. No patient identifiers such as identification numbers or full names were collected. The data were analyzed anonymously. The questionnaire included the following sections: basic demographic information, respiratory symptoms, comorbidities, medication regimen for COPD, vaccination status, knowledge of vaccination, and intention to vaccinate. Invalid questionnaires were defined as having any of the following: (1) more than two-thirds of the questions were not answered, (2) all options in the questionnaire were the same, and (3) all answers in the questionnaire were repeated regularly.

The degree of dyspnea was assessed using the modified British Medical Research Council (mMRC) scale, which was divided into: 0 points, no obvious dyspnea except during strenuous exercise; 1 point, shortness of breath at times when walking fast or going up a gentle slope; 2 points, need to stop and breathe when walking slower than peers or walking at their own pace on level ground due to dyspnea; 3 points, need to stop for rest when walking on level ground for 100m or several minutes; and 4 points, shortness of breath when they were unable to leave the room or change clothes due to obvious breathlessness¹⁷. The degree of cough, expectoration, chest tightness, wheezing, and COPD influence on home activities, ability to go outside, sleep quality, and energy level were divided into six levels according to the cough extent rating scale¹⁸: 0 points, no; 1 point, mild; 2 points, moderate; 3 points, severe; 4 points, very severe; and 5 points, worst.

The questionnaire was pre-tested to determine its reliability and feasibility. One hundred patients with COPD were randomly selected and underwent a formal survey. The reliability and validity analyses were performed separately for each scale.

Power size calculation

The minimum sample size was calculated assuming that the acceptance rate of the COVID-19 vaccine was 50%. To estimate the probability of vaccine acceptance within 4% of the true value, the calculation formula of the sample size was as follows:

Among them, the confidence level Z (α/2) was 1.96, and the allowable error of δ was 0.04. According to this formula, the minimum sample size was 601. Considering the presence of invalid questionnaires, the sample size was increased by 10–20%.

Statistical analysis

Exploratory factor analysis (EFA) was conducted to assess construct validity using Principal Axis Factoring¹⁹. The Kaiser–Meyer–Olkin (KMO) and Bartlett’s tests of sphericity were performed to measure the factorability of the data matrix. Cronbach’s alpha was used to estimate reliability. The KMO value must be greater than 0.60, and Bartlett’s test value must be significant (P < 0.001) to indicate questionnaire adequacy²⁰. The Cronbach’s alpha coefficient must be ≥ 0.6 to indicate the questionnaire reliability²¹.

Categorical data were expressed as the number of cases and percentages (%). The chi-square (χ²) test was performed for univariate analysis. Multivariate logistic regression analyses were conducted to identify the relevant factors affecting COVID-19 vaccination. Predictors were represented using odds ratio (OR) and 95% confidence intervals (CI). SPSS 26.0 was used for data collation and statistical analysis; P < 0.05 was considered statistically significant.

Institutional review board statement

This study was approved by the Ethics Committee of the Shengjing Hospital of China Medical University (No. 2022PS1182K) and conducted according to the Declaration of Helsinki.

Informed consent

Informed consent was obtained from each participant before administering the questionnaires.

Basic characteristics of the survey respondents and factors affecting the COVID-19 vaccination rate

The KMO value was 0.942 and the Bartlett’s sphericity test value was significant (P < 0.001), indicating high validity. The Cronbach’s alpha was 0.889, indicating high reliability. The total number of individuals that participated was 1936; however, 38 individuals were excluded because they did not meet the diagnostic criteria for COPD. Altogether, 1898 questionnaires were completed, of which 24 were regarded as invalid, and finally 1,874 valid questionnaires were obtained (validity rate of 98.74%). The age of the patients was mostly 55–65-years (n = 564, 30.10%); the height was mostly 160–170cm (n = 721, 38.47%); the weight was mostly 50–60kg (n = 596, 31.80%); the patients were mostly male, accounting for 56.78% (n = 1064); patients in junior high school accounted for the largest proportion (n = 649, 34.63%); and married patients accounted for the majority of patients (n = 1290, 68.84%). Most patients needed care (n = 1476, 78.76%), while unattended patients accounted for only 21.24% (n = 398). Cumulatively, 77.16% (n = 1446) of the patients were covered by rural cooperative or urban medical insurance, 19.69% (n = 369) were self-financed for medical care, and 3.15% (n = 59) were covered by public medical care. Most of the families had per capita monthly incomes of 3,000–5,000 yuan (n = 900, 48.03%), and 36.87% (n = 691) of the patients had a history of allergy. A history of smoking was present in 52.56% of the patients (n = 985), with the majority having a smoking history of 10–20years (n = 252, 25.58%), and smoked 5–10 cigarettes per day (n = 322, 32.69%). Univariate analysis revealed that age (P < 0.001), marital status (P < 0.001), monthly income (P < 0.001), habitual residence (P < 0.001), household income (P = 0.007), history of allergy (P < 0.001), smoking status (P < 0.001), years of smoking (P < 0.001), and number of cigarettes smoked per day (P < 0.001) were the key factors affecting COVID-19 vaccination rate. Details are presented in Table 1.

Disease status of the survey respondents and factors affecting the COVID-19 vaccination rate

In the survey, more than half of the patients were diagnosed with COPD for the first time (n = 1114, 59.45%), and for patients who had been diagnosed with COPD before, the duration of illness was mostly < 5years (n = 321, 42.24%); nearly half of the patients indicated that they did not have much knowledge regarding COPD (n = 963, 51.39%), and 40.00% (n = 937) had 1–2 acute exacerbations of the disease in the past year, while half of the patients were not hospitalized for acute exacerbation (n = 852, 45.46%); nearly one-third of the patients did not use medication for COPD regularly (n = 554, 29.56%). We recommended treatments based on established guidelines for patients who did not receive regular treatment. 33.62% of the patients (n = 630) and 15.64% of the patients (n = 293) underwent home oxygen therapy and used non-invasive ventilation machines, respectively; more than half of the patients considered their current health status fair (n = 1051, 56.08%). After comparisons, we established whether COPD was diagnosed for the first time (P = 0.002), duration of COPD (P < 0.001), number of acute exacerbations of COPD in the last year (P < 0.001), number of hospitalizations for acute exacerbations in the last year (P < 0.001), comorbidities with other systemic diseases (P < 0.001), the severity of the current disease, including the degree of dyspnea (P < 0.001), degree of cough (P = 0.048), degree of expectoration (P < 0.001), degree of wheezing (P < 0.001), home activities influenced by COPD (P < 0.001), ability to go outside (P < 0.001), sleep quality (P = 0.005), energy level (P < 0.001), and current physical condition (P < 0.001), regularity of medication (P < 0.001), home oxygen therapy (P < 0.001), and application of non-invasive ventilation machines (P < 0.001) were factors that significantly different in the COVID-19 vaccination rate. The details are presented in Table 2.

Vaccination status of related vaccines among the survey respondents and factors affecting COVID-19 vaccination rate

Most patients had not been injected with the relevant vaccines (n = 936, 49.95%), and among those who had been injected with the relevant vaccines, the influenza vaccine had been administered to the highest number of patients (n = 688, 36.71%). The results of the univariate analysis revealed statistically significant differences in the COVID-19 vaccination rate based on whether other vaccines had been injected and whether an adverse reaction had occurred after the injection of other vaccines (both P < 0.001). The details are presented in Table 3. Approximately a third of the patients experienced adverse reactions after vaccination (n = 281; 29.18%). The most frequent adverse reaction was malaise (n = 203, 72.24%) followed by digestive tract symptoms (n = 197, 70.11%). The adverse reactions of influenza, pneumonia, or herpes zoster vaccines in patients with COPD are shown in Fig.1.

Reasons for patients with COPD receiving or not receiving the COVID-19 vaccine

The vast majority of the patients were currently inoculated with the COVID-19 vaccine (n = 1473, 78.60%); among them, 50.31% (n = 741) had received three doses of the COVID-19 vaccine, 42.50% (n = 626) had received two doses of the COVID-19 vaccine, and only 7.20% (n = 106) had received one dose of COVID-19 vaccine (Fig.2A,B). The reason for vaccination was self-selected as the need for disease prevention (n = 1050, 70.47%). “Fear of causing exacerbation or recurrence of the disease of COPD” (n = 113, 45.75%) was foremost among the reasons for not having received the COVID-19 vaccine yet. Only 33.14% (n = 629) of the patients were worried about the exacerbation of COPD after vaccination prior to receiving the vaccine, and the most common concern was “adverse reactions after vaccination” (n = 900, 47.42%). Most patients had no concerns regarding the COVID-19 vaccine (n = 921, 48.52%). The reasons for this are summarized in Table 4.

Attitudes of the respondents toward the COVID-19 vaccine and factors affecting COVID-19 vaccination rate

Nearly half of the patients consulted medical staff regarding COVID-19 vaccination (n = 913, 48.72%). Most patients who consulted medical staff received answers (n = 634, 69.44%), while only a few patients found the consultation method “inconvenient” or “very inconvenient” (n = 171, 18.73%). Medical staff recommended the COVID-19 vaccine to most patients (n = 1270, 67.77%). The vast majority of patients with COPD had not yet contracted COVID-19 pneumonia (n = 1730, 92.32%). More than half of the patients were concerned about contracting COVID-19 (n = 1039, 55.44%), and 87.09% (n = 1584) believed that the vaccine could prevent COVID-19 infection, and 86.88% believed that the current COVID-19 vaccine was “very safe” (n = 538, 28.71%) or “safe” (n = 1094, 58.38%). The results demonstrated statistically significant differences in COVID-19 vaccination rates among those who had been infected with COVID-19 (P < 0.001), those who were concerned about contracting COVID-19 (P = 0.001), those who believed that vaccines could prevent COVID-19 (P < 0.001), their views on current vaccine safety (P < 0.001), whether they received answers after consulting medical staff about COVID-19 vaccination (P = 0.001), and whether medical staff recommended COVID-19 vaccination (P < 0.001). The attitudes of the respondents toward the COVID-19 vaccine and the factors affecting the COVID-19 vaccination rate are presented in Table 5.

Brands and number of COVID-19 vaccinations in patients with COPD

The COVID-19 vaccines administered to patients with COPD include CoronaVac, Sinopharm/BIBP (Beijing Institute of Biological Products Co., Ltd.), Sinopharm/WIBP (Wuhan Institute of Biological Products Co., Ltd), CanSinoBio, Zhifei Longcom, KCONECAVAC, and IMBCAMS. In total, 1473 patients with COPD received one dose, 1367 patients with COPD received two doses, and 741 patients with COPD received three doses. The most commonly administered vaccines for the first dose in patients with COPD were CoronaVac (n = 551, 37.41%) and Sinopharm/BIBP (n = 507, 34.42%). The most commonly administered vaccines for the second dose in patients with COPD were CoronaVac (n = 507, 37.09%) and Sinopharm/BIBP (n = 441, 32.26%). The most commonly administered vaccines for the third dose in patients with COPD were CoronaVac (n = 276, 37.25%) and Sinopharm/BIBP (n = 242, 32.66%) (Fig.3).

Adverse reactions after receiving the COVID-19 vaccine

Only a small number of patients experienced adverse reactions after receiving the COVID-19 vaccine: 18.94% (n = 279), 16.39% (n = 224), and 12.55% (n = 93) after the first, second, and third doses, respectively. Most adverse reactions occurred within 48h of injection for the first (n = 171, 61.29%) and second doses (n = 129, 57.59%), whereas adverse reactions occurred primarily within 24h after the third vaccination (n = 27, 29.03%) (Fig.4). Adverse reactions were similar for all three doses of the COVID-19 vaccine, with very few systemic adverse reactions. The most adverse reactions were “weakness” or “muscle soreness” in 74.91% (n = 209) and 71.33% (n = 199) for the first injection and 59.82% (n = 134) and 67.41% (n = 151) for the second injection. The adverse reactions after the third injection more often manifested as “muscle soreness” or “redness, swelling, and pain at the injection site” in 54.84% (n = 51) and 53.76% (n = 50) patients (Fig.5).

Multifactorial analysis of COPD patients influencing the COVID-19 vaccination

Using COVID-19 vaccination as the dependent variable, all statistically significant indicators in the univariate analysis were included as independent variables. To eliminate possible associations between the variables, a multicollinearity diagnosis was performed before including them in the multivariate analysis. Our results indicated that tolerance was greater than 0.1, and the variance inflation factor was less than 5. There was no significant collinearity among the factors. Stepwise regression was adopted in the multivariate analysis and the collinearity of the variables was further restricted. The results of multivariate logistic regression analyses (Table 6) revealed that the factors that influenced COVID-19 vaccination were: age being 75–85years (OR = 1.822, 95% CI 1.023–3.246) (P = 0.042) and > 85years (OR = 2.609, 95% CI 1.001–6.802) (P = 0.050), 3–4 times of acute exacerbations in the last year (OR = 1.693, 95% CI 1.222–2.555) (P = 0.012), comorbid cardiovascular system diseases (such as hypertension, coronary artery disease, and heart failure) (OR = 1.544, 95% CI 1.185–2.010) (P = 0.001), and comorbid endocrine system diseases (such as diabetes and osteoporosis) (OR = 1.762, 95% CI 1.327–2.339) (P < 0.001), not taking regular medication for COPD (OR = 1.357, 95% CI 1.032–1.784) (P = 0.029), application of non-invasive ventilation machines (OR = 1.469, 95% CI 1.063–2.029) (P = 0.020), perceiving current health condition as deteriorating (OR = 1.863, 95% CI 1.203–2.886) (P = 0.005), perceived current COVID-19 vaccine as unsafe (OR = 2.813, 95% CI 1.854–4.269) (P < 0.001) and very unsafe (OR = 2.215, 95% CI 1.022–4.802) (P = 0.044), medical staff did not provide a clear answer as to whether they recommended COVID-19 vaccination (OR = 1.664, 95% CI 1.242–2.229) (P = 0.001), medical staff did not recommend the COVID-19 vaccine (OR = 3.695, 95% CI 2.449–5.575) (P < 0.001), fear of adverse reactions after vaccination (OR = 1.575, 95% CI 1.1196–2.074) (P = 0.001), and exacerbation of COPD (OR = 1.811, 95% CI 1.3776–2.382) (P < 0.001).

Currently, COVID-19 remains sporadic, and vaccination is a simple and effective method to prevent the further spread of COVID-19 and reduce hospitalization and mortality²². Therefore, exploring the factors that affect vaccination of COPD patients with COVID-19 helps reduce mortality during sporadic epidemics.

As of June 16, 2022, China has received 3.393 billion doses of the COVID-19 vaccine, with 1,292,334 million people vaccinated, accounting for 91.66% of the total number of people covered and 89.31% of the total number of people vaccinated. Although the national vaccination rate has exceeded 90%, a gap remains between the total number of vaccinated people and the target vaccination rate, especially among people with underlying diseases. According to our research, the COVID-19 vaccination rate of patients with COPD was 78.60%, which was higher than a survey of COVID-19 vaccination willingness in China in January 2022 (67.10%)²³. However, this is still lower than the acceptance rate of the COVID-19 vaccine in Hungary (86.57%) in 2022¹². The reason may be that in Hungary, doctors, healthcare workers, professional organizations, and civil society informed patients of the benefits of vaccination and adopted strong social measures to increase vaccine coverage. Therefore, the vaccination rate of patients with COPD requires further improvement.

This study observed no statistical difference in the impact of sex on the COVID-19 vaccination rate, in contrast to a previous domestic study that indicated that men were more likely to refuse vaccination²⁴. In that study, Wu et al. established that vaccination rates were associated with increased awareness of vaccines and decreased confidence in disease-related conspiracy theories among men, whereas in our study population, there were no significant differences between men and women in terms of their perceptions of how safe vaccines are and whether they can prevent COVID-19. Consistent with the results of a global survey²⁵, our study established that the vaccination rate in patients aged 55–65years old was the highest (82.98%). However, this was different from the results of a study conducted in the United States²⁶. This study established that the vaccination rate in patients aged 65–75years old, 75–85years old, and > 85years old decreased to 70.70%, 63.39%, and 48.57%, respectively. This might be related to the lower acceptance rate of vaccination due to reduced mobility in elderly patients. Unlike previous studies^27,28, we established that the income and education levels of patients with COPD did not have a significant impact on the vaccination rate, which may be related to China’s COVID-19 vaccination strategy and the lower risk of COPD among Chinese people with middle or high school, university, or higher education⁹.

Furthermore, we established that the vaccination rate of the COVID-19 vaccine was lower in COPD patients with comorbid underlying diseases, which is consistent with a cross-sectional study by Tsai et al.²⁹. Nevertheless, we established a statistically significant difference in the vaccination rate of patients with comorbid cardiovascular and endocrine diseases compared to those with other comorbid systemic diseases, which may be related to the decreased perception of vaccine safety in COPD patients with comorbid diseases. Concurrently, we established that the physical condition, disease treatment, and degree of disease in patients with COPD also had a significant effect on the vaccination rate. The number of acute episodes of COPD (3–4 times in the last year) had a significant effect on the vaccination rate of the COVID-19 vaccine compared with the number of other acute episodes. This may be because few acute episodes lead to higher vaccination rates as a result of greater patient confidence in their health status, whereas many episodes of the disease lead to a significant decrease in patients’ willingness to be vaccinated. It is believed that patients with deteriorating current health, using non-invasive ventilation machines, and not regularly taking medication to control their COPD may have lower vaccination rates due to the inconvenience of traveling or fear of disease deterioration after vaccination. Unlike a study on the willingness to vaccinate against COVID-19 in a population with COPD in Beijing conducted by Song et al.³⁰, we did not identify any effects of influenza and pneumococcal vaccinations on the vaccination rate of the COVID-19 vaccine. This may be due to the COVID-19 pandemic, leading to varying levels of awareness among the population regarding influenza or pneumococcal and COVID-19 infections.

Consistent with Liu et al.³¹, we established that concerns about the efficacy and safety of the COVID-19 vaccine significantly reduced vaccination rates. Compared with medical staff recommending COVID-19 vaccination, failure to provide a clear response or medical staff not recommending vaccination significantly reduced the COVID-19 vaccination rate, which is in line with previous studies^32,33. Moreover, we established that fear of adverse reactions after vaccination and COPD exacerbation led to a decrease in vaccination. Therefore, health education and positive recommendations by medical staff are crucial for reducing the psychological burden on COPD patients, increasing COVID-19 vaccinations, further reducing hospitalization and severe disease rates, and reducing the risk of secondary infection.

The sample size of this survey was relatively large, covering the COPD population from all regions of the country. Therefore, it reflects the actual situation adequately. However, this study has some limitations. This survey used an anonymous questionnaire on the Internet, and there may have been a reporting bias. With the adjustment of the COVID-19 epidemic policy, the degree and willingness of the population with COPD to be vaccinated against COVID-19 may change. The results of this study are time-sensitive.

Although the COVID-19 pandemic has ended, it remains sporadic. COVID-19 is a risk factor for a poor prognosis in patients with COPD, and vaccination is a simple and effective way to reduce mortality. Previous studies have mostly focused on the normal population, and the sample sizes of studies on patients with COPD were relatively small. Additionally, most previous studies were conducted during the outbreak of the COVID-19 pandemic, when the selection of vaccine types was relatively small and safety had not been determined. Our study was focused on patients with COPD, and the sample size was relatively large. During the current sporadic COVID-19 epidemic, it is helpful to promote the vaccination of the COVID-19 vaccine and even the Streptococcus pneumoniae vaccine in COPD patients, and thereby facilitate the further reduction of mortality.

COVID-19:

Coronavirus disease 2019

COPD:

Chronic Obstructive Pulmonary Disease

GOLD:

Global Initiative for Chronic Obstructive Lung Disease

FEV1:

Force expiratory volume in 1s

FVC:

Forceful lung volume

mMRC:

Modified British Medical Research Council

EFA:

Exploratory factor analysis

KMO:

Kaiser–Meyer–Olkin

OR:

Odds ratio

CI:

Confidence intervals

Author notes

1. These authors contributed equally: Mingzhe Li, Qiang Zhang, Yuanyi Yue, Zhong He and Jianwei Fang.

Authors and Affiliations

1. Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, 110022, China

   Mingzhe Li,Qiang Zhang,Zhong He&Rui Zheng

2. Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China

   Yuanyi Yue

3. Clinical Trial Department, Shengjing Hospital of China Medical University, Shenyang, China

   Jianwei Fang

Contributions

R.Z. designed, conceived, supervised, and obtained funding for this study. M.Z.L. collected data, performed the data analysis, and drafted the manuscript. Y.Y.Y. collected data and information, performed the data analysis, and supervised the study. Z.H. contributed to picture drawing. J.W.F. performed the data analysis and interpreted the data. Q.Z. performed the data analysis, validated the data, and revised the manuscript.

Corresponding author

Correspondence to Rui Zheng.

Competing interests

The authors declare no competing interests.

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