Safety and reported adverse effects of coronavirus disease-2019 (COVID-19) vaccines in patients with rheumatic diseases

Abstract

Background

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptoms and severity of COVID19 are variable.

Aim of the work

To evaluate the effectiveness and to identify side effects of the COVID-19 vaccines among Egyptian patients with autoimmune rheumatic diseases (RDs).

Patients and methods

The study included 126 patients with various RDs and 200 control. Detailed medical history was recorded with special concern regarding COVID-19 vaccination, types, doses, side effects, post-vaccination infection and treatment.

Results

In patients, BBIBP-CorV (Sinopharm) was the most frequent vaccine 42.3 % (n = 52); CoronaVac (Sinovac) 22 % (n = 27); ChAdOx1 (AstraZeneca) 17.9 % (n = 22); BNT162 (Pfizer BioNTech) 14.6 % (n = 18); Sputnik V 1.6 % (n = 2) and Ad26.COV2-S (Johnson & Johnson) 1.6 % (n = 2). Regarding the control, 34.4 % (n = 62) received AstraZeneca; 26.1 % (n = 47) Sinopharm; 16.7 % (n = 30) Pfizer; 11.7 % (n = 21) Sinovac; 6.7 % (n = 12) Sputnik; 3.3 % (n = 6) Johnson & Johnson and 1.2 % (n = 2) mRNA1273 (Moderna). COVID-19 infection decreased after vaccination from 32 (25.4 %) to 7 (5.6 %), and from 162 (81.0 %) to 85 (42.7 %) in RD patients and the control respectively. ICU admission decreased from (6.3 %) among RD patients and from (1.3 %) in control to 0 % after vaccination in both groups. In RD patients, body ache was the commonest reported vaccine adverse effect (44.4 %). Pain at the injection site was the commonest among control (77 %). ChAdOx1 (AstraZeneca) had the highest incidence of side effects, mRNA1273 (Moderna) showed the lowest.

Conclusion

COVID-19 vaccine was effective in decreasing infection and disease severity in RDs patients and control, with similar, mild adverse effects.

1. Introduction:

Coronavirus disease-2019 (COVID-19) is a contagious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptoms and severity of COVID-19 are variable from being asymptomatic to respiratory failure and death. Symptoms mainly include fever, cough, myalgias, diarrhea, anosmia and dyspnea [1].The impact of the SARS-CoV2 pandemic is negative on the quality of life of rheumatoid arthritis (RA) patients from Benin [2]. In Turkey, low dose rituximab was found effective in the treatment of RA and none of the patients developed severe COVID-19 infection requiring hospitalization [3]. Most rheumatic diseases (RDs) patients had complete symptom resolution by day 15 after COVID-19 onset. However, 25 % experienced symptom for a month and 10 % up to 3 months [4].Moreover, the autoimmune property of this emerging virus raises questions about its role in the pathogenesis of RDs [5]. How the rheumatology patients were managed in Egypt during the pandemic was similar to outlines considered world-wide [6].

The COVID-19 vaccines are recommended for their role in reducing the spread of COVID-19 [7] and reducing the severity and death caused by it [8].Different types of COVID vaccines are available now for use worldwide including:BNT162 (Pfizer BioNTech, New York, NY, USA), ChAdOx1 (AstraZeneca, Oxford, UK), mRNA1273 (Moderna, Cambridge, MA, USA), and Ad26.COV2-S (Johnson & Johnson, New Brunswick, NJ, USA), BBIBP-CorV (Sinopharm, Beijing, China), CoronaVac (Sinovac, Beijing, China), Sputnik V (Gamaleya, Moscow, Russian) [9].Many adverse events may develop after receiving the vaccine, these unfavorable events were worrying for population especially those with autoimmune rheumatic diseases [10]. Postvaccine side effects include mainly fatigue, fever, headache, pain at the injection site, nausea and diarrhea [11]. However, the Egyptian Rheumatologists supported the broad safety of the COVID-19 vaccine in favor of the global benefit from mass vaccination [12] and the majority agreed that they will recommend it to their RD patients [13]. Gaps remain in the evidence of the COVID-19 vaccines safety in RDs patients although it was found to be relatively safe [14].

Although COVID-19 vaccines trials did not include autoimmune rheumatic patients, and vaccine efficacy and adverse effects in this group of patients are not yet clear. But the American College of Rheumatology (ACR) guidelines recommended vaccination of these patients to decrease the probability of COVID infection [15]. However, patients with autoimmune diseases may have a diminished immune response due to the autoimmune disease or its therapy [16].

The aim of this work was to evaluate the effectiveness and to identify side effects of COVID 19 vaccine among Egyptian patients with autoimmune rheumatic diseases in comparison to the general population.

2. Patients and methods

This study included 126 Egyptian patients with RDs and 200 matched healthy adult participants as a control group. Patients were collected randomly from the rheumatology outpatient clinic and inpatient of internal medicine and rheumatology department, Ain Shams University hospitals. Other participants were collected randomly from the community. The study was approved from the Ethical Committee of Scientific Research, Faculty of Medicine, Ain Shams University (FMASU R 166/2022). All participants provided their informed consent.

Detailed medical history was taken from all participants including age, gender, and presence of comorbidities, drug intake, previous COVID infection and treatment place. There was a special concern regarding history of COVID19 vaccination, type of vaccine received, number of doses, side effects, post vaccination COVID19 infection and place of treatment. Infants, children, pregnant and lactating females were excluded.

Statistical analysis: Collected data were tabulated and analyzed using the statistical package for social sciences (SPSS) version 25.0. Variables were presented as frequencies and percentages, mean ± standard deviation and range. A comparison was done using Chi-square. P value < 0.05 was considered significant.

3. Results

The patients’ mean age was 41.8 ± 11 years, they were 104 females and 22 males (F:M 4.7:1). While the mean age of the control 40 ± 11 years, 160 females and 40 males (F:M 4:1) (p = 0.99, and p = 0.6). COVID-19 infection before and after vaccination and place of treatment during the infection in RDs patients and control are presented in Table 1 . The patients had the following RDs: 59 (46.8 %) had RA; 43 (34.1 %) systemic lupus erythematosus (SLE); 4 (3.2 %) ankylosing spondylitis (AS), 4 (3.2 %) Behçet disease; 5 (4 %) antiphospholipid syndrome (APS), 5 (4 %) mixed connective tissue disease (MCTD); 3 (2.4 %) vasculitis; 1 (0.8 %) Scleroderma and interstitial pulmonary fibrosis (IPF), 1 (0.8 %) dermatomyositis and another (0.8 %) psoriatic arthritis (PsA).

Table 1.

Corona-virus disease-2019 (COVID-19) infection before and after vaccination and place of treatment during the infection in rheumatic diseases (RDs) patients and control.

Parameter n (%)/mean ± SD	Control (n = 200)	RD patients (n = 126)	p
Female	160 (80)	104 (82.5)	0.6
Age (years)	40 ± 11	41.8 ± 11	0.99
Before vaccination
COVID-19 infection			<0.001
	162 (81)	32 (25.4)
Place of treatment:
Home	146 (90.1)	27 (84.7)	<0.001
Hospital	14 (8.6)	3 (9.2)
ICU	2 (1.3)	2 (6.3)
Vaccination
>1 vaccine			0.013
	19 (9.5)	3 (2.4)
Fully vaccinated			0.41
	179 (89.5)	109 (86.5)
After vaccination
COVID-19 infection			<0.001
	85 (42.5)	7 (5.6)
Place of treatment:
Home	76 (89.4)	5 (71.4)	<0.001
Hospital	7 (10.6)	2 (28.5)

RD: rheumatic disease, COVID-19: Corona-virus disease-2019. Bold values are significant at p < 0.05.

Thirty-two (25.4 %) RDs patients were infected with COVID 19 before taking vaccine, while dramatically decreased to be 7 (5.6 %) after vaccination. ICU admission decreased from 6.3 % (n = 2/32) to 0 % after vaccination although home treatment decreased from 84.7 % (n = 27/32) to 71.4 % (n = 5/7) and hospitalization increased from 9.2 % (n = 3/32) to 28.5 % (n = 2/7). Of the 200 control, 162 (81 %) caught COVID19 infection before vaccine that was 85 (42.7 %) post vaccination. ICU admission decreased from 1.3 % (n = 2/162) to 0 % post-vaccination. However, home treatment decreased from 146/162 (90.1 %) to 76/85 (89.41 %), hospitalization increased from 14/162 (8.6 %) to 7/85 (10.6 %) after vaccination.

BBIBP-CorV (Sinopharm) was the most frequent vaccine taken by patients 42.3 % (n = 52), followed by CoronaVac (Sinovac) 22 % (n = 27) then ChAdOx1 (AstraZeneca) 17.9 % (n = 22);BNT162 (Pfizer BioNTech) 14.6 % (n = 18); Sputnik 1.6 % (n = 2) and Ad26.COV2-S (Johnson & Johnson) 1.6 % (n = 2). 3 (2.4 %) patients received more than one vaccine, 109 (86.5 %) reached full vaccinated status. Regarding the control, 34.4 % (n = 62) received ChAdOx1 (AstraZeneca); 26.1 % (n = 47) BBIBP-CorV (Sinopharm); 16.7 % (n = 30) BNT162 (Pfizer BioNTech) 11.7 % (n = 21) CoronaVac (Sinovac); 6.7 % (n = 12) Sputnik; 3.3 % (n = 6) Ad26.COV2-S (Johnson & Johnson) and 1.2 % (n = 2) Moderna. 19 (9.5 %) received >1 vaccine, 179 (89.5 %) reached full vaccinated status.

Adverse effects after receiving the vaccine for patients and control are presented in Table 2 .There was a significant lower frequency of pain at the site of injection, fever, body ache, rhinorrhea, pharyngitis, dyspnea, chest pain, cough and abdominal pain in patients than control.

Table 2.

Side effects of coronavirus disease 2019 (COVID-19) vaccines among rheumatic diseases patients and control.

Side effect	Control (n = 200)	RD patients (n = 126)	p
Pain at injection site	154 (77)	37 (29.3)	<0.001
Swelling	74 (37)	40 (31.7)	0.33
Redness	67 (33.5)	34 (27)	0.22
Fever	95 (47.5)	41 (32.5)	0.008
Headache	74 (37)	52 (41.3)	0.44
Body aches	118 (59)	56 (44.4)	0.01
Rhinorrhea	24 (12)	4 (3.2)	0.006
Nasal congestion	12 (6)	5 (4)	0.42
Pharyngitis	25 (12.5)	4 (3.2)	0.004
Chest pain	26 (13)	4 (3.2)	0.003
Cough	33 (16.5)	5 (4)	0.001
Dyspnea	23 (11.5)	4 (3.2)	0.008
Hemoptysis	2 (1)	0 (0)	–
Abdominal pain	30 (15)	7 (5.6)	0.009
Diarrhea	18 (9)	9 (7.1)	0.42

RD: rheumatic disease. Bold values are significant at p < 0.05.

Comparing different types of vaccines side effects are shown in Table 3 .

Table 3.

Frequency of side effects of different types of coronavirus disease 2019 (COVID-19) vaccines in rheumatic diseases patients.

Adverse effects	COVID-19 vaccines in RD patients (n = 126)
	BBIBP-CorV (Sinopharm)	CoronaVac (Sinovac)	ChAdOx1 (AstraZenec)	BNT162 (Pfizer)	Sputnik	Ad26.COV2-S (J & J)	p
Pain (inj.site) (n = 37)	3 (8.1)	5 (13.5)	13 (35.1)	14 (37.8)	1 (2.7)	1 (2.7)	<0.001
Swelling (n = 40)	2(5.4)	5 (13.5)	14 (37.8)	13 (35.1)	1 (2.7)	2 (5.4)	<0.001
Redness (n = 34)	1(3.2)	3 (9.7)	12 (38.7)	12 (38.7)	1 (3.2)	2 (6.5)	<0.001
Fever (n = 41)	3 (7.9)	3 (7.9)	15 (39.5)	13(34.2)	2(5.3)	2 (5.3)	<0.001
Headache (n = 52)	12 (24.5)	8 (16.3)	13 (26.5)	12 (24.5)	2 (4.1)	2 (4.1)	<0.001
Body aches (n = 56)	15(28.3)	8 (15.1)	15 (28.3)	12 (22.6)	1 (1.9)	2 (3.8)	0.002
Rhinorrhea (n = 4)	0 (0)	0 (0)	0 (0)	4 (100)	0 (0)	0 (0)	–
Nasal Cong. (n = 5)	0 (0)	0 (0)	1 (25)	3 (75)	0 (0)	0 (0)	–
Pharyngitis (n = 4)	0 (0)	0 (0)	0 (0)	3 (100)	0 (0)	0 (0)	–
Chest Pain (n = 4)	0 (0)	0 (0)	4 (100)	0 (0)	0 (0)	0 (0)	–
Cough (n = 5)	0 (0)	1 (20)	3 (60)	1(20)	0 (0)	0 (0)	–
Dysnea (n = 4)	1 (25)	0 (0)	3 (75)	0 (0)	0 (0)	0 (0)	–
Abd. pain(n = 7)	0 (0)	1 (14.3)	3 (42.9)	3 (42.9)	0 (0)	0 (0)	0.07
Diarrhea (n = 9)	0 (0)	1 (11.1)	4 (44.4)	3 (33.3)	1 (11.1)	0 (0)	0.006

COVID-19: Corona-virus disease-2019, RD: rheumatic disease. Bold values are significant at p < 0.05.

4. Discussion

Recently, different types of COVID vaccines became available. Safety and effectiveness of the vaccine greatly contribute to expand its use, helping in reducing the viral spread. So, studying the vaccine adverse effects and efficacy are important issues to reassure the recipients and improve their awareness [17]. Patients with rheumatic diseases may show diminished immune response because of their illness or its therapy. Therefore, they are more risky for infections, hospitalizations and deaths [16].

In the present study, out of 126 RD patients, 25.4 % were infected with COVID19 before taking vaccine, of them, 9.2 % needed hospitalization and 6.3 % needed ICU admission. In line, Assar et al. [18] reported 22.1 % of 1000 studied RD patients recorded COVID19 infection, 17.2 % of them needed hospitalization and 6 % needed ICU admission.

COVID19 infection in RD patients was significant less frequent than in control before or after vaccination. That may reflect less susceptibility of these patients to infection [19] and these results being explained by patients close adherence to treatment, increased worrying and isolation fearing from catching infection. Another explanation by Braun-Moscovici et al. [20] was suggested, that the immune-modulating role of anti-rheumatic drugs gives it antiviral prophylactic or therapeutic effect. Similarly, Poustchi et al. [21] revealed that COVID-19 infection in rheumatic patients was the same as other participants. Also, Favalli et al. [22] found that RDs did not show increased liability to develop COVID19 infection.

Hospitalization among infected RD patients was significantly higher than control before and after vaccine with higher ICU admission before vaccination. In agreement, D’Silva et al. [23] found increased need for ICU in RDs patients. And in partial agreement, Assar et al. [18] reported that RDs patients were not at higher risk for COVID-19 although receiving immunosuppressant drugs and the prognosis was not worse compared with others.

Although not all RD patients achieved the full vaccinated status, there was dramatic decrease in both infection and need for ICU after vaccination. That reflected the efficacy of vaccine in decreasing infection as well as disease severity. This comes in concordance with Machado et al. [24] who concluded that COVID19 infections in RD patients after vaccination occurred less frequent especially in fully vaccinated ones. Moreover, Bieber et al. [25] reported decrease in both infection and need to be hospitalized between vaccinated RD patients. Regarding control, infection and need for ICU were decreased after receiving vaccine. In agreement, Polack et al. [26] compared vaccine versus placebo injection and revealed 95 % protection against Covid-19 in vaccinated persons >16 years of age.

Current findings go in hand with those of Thomas et al. [27] who showed that vaccine was effective in preventing serious illness by 96.7 %. There were reassuring results while studying adverse events of the vaccine. Most of patients with RDs complained of mild and well tolerated side effects, as found by Machado et al. [24] and Braun-Moscovici et al. [28] who showed that the vaccine is safe in their patients, only minor side effects were reported.

Among the recorded adverse effects in RD patients, bodyache was the commonest in 44.4 % followed by headache in 41.3 %, pain at site of injection in 33 %; fever in 32.5 %; swelling in 31.7 % and redness in 27 %. There was no life threatening events. In accordance, Machado et al. [24] and Li et al. [29] recorded vaccine adverse effects including pain at injection site in 19 %, body aches in 7 % and fever in 7 %. Similarly, Esquivel-Valerio et al. [30] and Furer et al. [31] provided reassuring results regarding vaccination of RD patients. As they demonstrated that localized pain, fatigue, headache and muscle ache were common post vaccine events with no serious events needed hospitalization.

In the control, pain at site of injection was the commonest adverse effect followed by body ache, fever, swelling, headache and redness. In harmony, Polack et al. [26] and Elgendy et al. [32] demonstrated similar post vaccination side effects.

It has been previously reported by Machado et al. [24] and Sattui et al. [33], that adverse effects in RD patients were comparable to control and were mostly mild. In accordance, Braun-Moscovici et al. [28] and Akiyama et al. [34], found that unfavorable events of different types of COVID vaccines in RD patients did not differ much from the control.

Trying to assess the safety of different types of vaccines, ChAdOx1 (AstraZeneca) vaccine recorded the highest incidence of local and systemic side effects while mRNA1273 (Moderna) recorded the lowest. On the contrary, Li et al. [29] and Meo et al. [35] concluded that mRNA1273 (Moderna) had higher incidence of side effects. Also Al Khames Aga et al. [36], reported that BBIBP-CorV (Sinopharm, Beijing, China) had the lowest incidence of side effects.

This study had some limitations; all information was reported by volunteers themselves that may give misleading results. Detecting immunogenicity after vaccine by measuring the antibody titer was not performed. Time of adverse events occurrence had not been recorded. Retrospective design did not give information about mortality either from the disease or the vaccine.

In conclusion, different types of COVID-19 vaccine were effective in decreasing both infection and severity of the disease in RD patients and control with nearly similar and mild adverse effects. This work supports the safety of COVID-19 vaccine and may reassure the rheumatologists and their patients regarding recommending the vaccine.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

CRediT authorship contribution statement

Fatma M. Aboud: Conceptualization, Writing - original draft, Writing - review & editing. Rasha S. Hussein: Methodology, Data curation, Formal analysis, Writing - review & editing. Rasha M. Hassan: Conceptualization, Writing - original draft, Writing - review & editing.

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.