Abstract
COVID-19 vaccination has been shown to be safe in patients with systemic lupus erythematosus (SLE), but data on vaccine-associated adverse events (AEs) during the antenatal and lactation period are scarce or lacking. We investigated COVID-19 vaccination-related AEs in pregnant SLE patients from the COVAD study, a global esurvey involving 157 collaborators from 106 countries. A total of 9201 complete responses were extracted. Among 6787 (73.8%) women, we identified 70 (1.1%) who were exposed to at least one COVID-19 vaccine dose during pregnancy, 11 with SLE. Delayed onset (>7 days) vaccine-related AEs were triangulated with disease activity, treatment changes due to flare after vaccination, and COVID-19 infections in vaccinated pregnant women. Health-related quality of life and physical function was recorded using PROMIS. Age of patients ranged from 28 to 39 years; 5/11 women were of Asian origin. None of these patients reported major vaccine AEs or change in the status of their autoimmune disease. Although minor AEs were common, they did not impair daily functioning, and the symptoms resolved after a median of 3 (IQR: 2.5–5.0) days. All patients reported good to excellent health status. No adverse pregnancy outcomes were reported. Importantly, none of the patients reported thrombotic events post-vaccination, which provides reassurance in a patient population with a high risk for cardiovascular comorbidity and thrombosis, especially in the presence of antiphospholipid antibodies or the antiphospholipid syndrome, a considerable portion of SLE patients. Our findings provide reassurance and can contribute to informed decisions regarding vaccination in patients with SLE and high-risk pregnancies due to their background autoimmune disease. The risk/benefit ratio of COVID-19 vaccination appears favourable, with vaccines both providing passive immunisation to the fetus and active immunisation to the mother with no signals of exacerbation of the mother's autoimmune disease.
Keywords: Systemic lupus erythematosus, Pregnancy, COVID-19, SARS-CoV-2 virus, Adverse events, Vaccines
Vaccinations comprise a part of the antenatal care of pregnant women, including patients with systemic lupus erythematosus (SLE) who are at increased risk of adverse pregnancy outcomes (APOs) [1]. While COVID-19 vaccination has been shown to be safe in patients with SLE [2], data on vaccine-associated adverse events (AEs) during the antenatal and lactation period are scarce or lacking [[3], [4], [5]]. We herein investigated the association between COVID-19 vaccination and AEs in pregnant SLE patients from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 study.
The COVAD 2 is a global e-survey involving 157 collaborators from 106 countries [6], that has gathered nearly 20,000 responses. Ethical approval for the COVAD study was obtained from the Institutional Ethics Committee of the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014. A total of 9201 complete responses were extracted on June 21st, 2022; among respondents, 6787 (73.8%) were women. We identified 70 (1.1%) women who were exposed to at least one COVID-19 vaccine dose during pregnancy, among those 11 with SLE (Supplementary Fig. S1).
Delayed onset (>7 days) vaccine-related AEs were extracted and triangulated with disease activity, treatment changes due to flare after vaccination, and COVID-19 infections in vaccinated pregnant women with SLE. Additionally, information on health-related quality of life and physical function was recorded using PROMIS at the time of survey completion.
Characteristics of the patients are depicted in Table 1 . Age ranged from 28 to 39 years; 5/11 women were of Asian origin. None of these patients reported major vaccine AEs, including four patients with self-reported active SLE prior to the vaccination. None of them reported any change in the status of their autoimmune disease, and no hospitalisation or special treatment was recorded. Six women experienced minor vaccine AEs; two of them had active disease prior to vaccination. Four patients reported COVID-19 infection; two of them while they were pregnant and post-vaccination and two prior to pregnancy and vaccination. All four patients experienced symptoms of their disease, but no overt SLE flare was reported. At the time of survey completion, all patients reported their general health as being good to excellent in all aspects evaluated. Importantly, no APOs were reported.
Fig. 1.
Timeline showing COVID-19 vaccination and vaccination-related minor adverse events in relation to gestational and post-partum periods in eleven pregnant/lactating women with systemic lupus erythematosus.
Table 1.
Characteristics of 11 patients with SLE who received COVID-19 vaccination during pregnancy.
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 | Patient 10 | Patient 11 | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age (years) | 32 | 33 | 31 | 28 | 30 | 32 | 31 | 33 | 31 | 32 | 39 |
| Country | Costa Rica | Dominican Republic | India | Nigeria | Philippines | Taiwan | Thailand | Thailand | Thailand | United Kingdom | Venezuela |
| Ethnicity | Hispanic | Hispanic | Indian | African (Black) | Asian | Caucasian (White) | Asian | Asian | Asian | Caucasian (White) |
Mixed |
| Comorbidities | Migraine, HA, ITP | Eosinophilic fasciitis | Tuberculosis | None | None | None | HA, ITP | None | None | None | None |
| Date of delivery | 26 Nov 2021 | 22 Mar 2022 | 20 Aug 2022 | 3 Feb 2022 | 4 Jan 2022 | 25 Oct 2021 | 10 Apr 2022 | 16 Feb 2022 | 23 Mar 2022 | 5 Mar 2022 | 15 Apr 2022 |
| Vaccine doses, type, timeline (see also Fig. 1) | 3 doses 6 Jul 2021: Pf; 27 Jul 2021: Pf; 28 Jan 2022: Pf |
3 doses 11 May 2021: Sino; 8 Jun 2021: Sino; 8 Jul 2021: Sino |
2 doses 26 May 2021: Covi; 20 Aug 2022: Covi |
2 doses 12 Oct 2021: OxAZ; 23 Nov 2021: OxAZ |
3 doses 4 Oct 2021: OxAZ; 4 Nov 2021: OxAZ; 11 Mar 2022: Pf |
2 doses 1 Aug 2021; 1 Sep 2021; vaccine types not specified |
3 doses 2 Jul 2021: OxAZ; 24 Sep 2021: OxAZ; 13 Jan 2022: Pf |
3 doses 18 Aug 2021: Pf; 9 Sep 2021: Pf; 22 Apr 2022: Pf |
3 doses 4 Aug 2021: Sino; 25 Aug 2021: Sino; 8 Jan 2022: Mo |
4 doses 1 Feb 2021: Pf; 1 May 2021: Pf; 1 Nov 2021: Pf; 22 Mar 2022: Mo |
2 doses 20 Aug 2021: Sp; 9 Sep 2021: Sp |
| Minor AE | No | Yes, after the 3rd dose: minor symptoms with no further clarification | No | No | Yes, after all doses: injection site (arm) pain and soreness, fever, chills, headache, fatigue, joint pains |
No | Yes, after all doses: minor symptoms with no further clarification |
Yes: minor symptoms with no further clarification | Yes: minor symptoms with no further clarification | Yes, after all doses: injection site (arm) pain and soreness, fever |
No |
| Major AE | No | No | No | No | No | No | No | No | No | No | No |
| Hospitalisation due to AEs | No | No | No | No | No | No | No | No | No | No | No |
| Disease activity prior to vaccination | Inactive disease | Unable to judge | Stable and manageable disease | Unable to judge | Inactive disease | Inactive disease | Stable and manageable disease | Stable and manageable disease | Inactive disease | Inactive disease | Stable and manageable disease |
| Treatment until vaccination | HCQ; no GCs | HCQ; AZA; no GCs | HCQ; SSZ; no GCs | HCQ; prednisone eq. <10 mg/day | HCQ; no GCs | HCQ; prednisone eq. <10 mg/day | HCQ; no GCs | HCQ; AZA; prednisone eq. <10 mg/day | HCQ; no GCs | HCQ; CYS-A; no GCs | HCQ; MTX; prednisone eq. <10 mg/day |
| Disease activity after vaccination | No change in SLE status | No change in SLE status | No change in SLE status | No change in SLE status | No change in SLE status | No change in SLE status | No change in SLE status | No change in SLE status | No change in SLE status | No change in SLE status | No change in SLE status |
| Treatment changes after vaccination | None | None | None | None | None | None | None | None | None | None | None |
| COVID positive test (date, symptoms, need for special treatments, days needed to resolve) | No | Yes, once: 4 Jan 2022 (a) |
No | No | No | No | Yes, once: 23 Mar 2021 (b) |
No | Yes, once: 3 Mar 2022 (c) |
No | Yes, once: 5 Apr 2021 (d) |
| Test for anti-SARS-CoV-2 antibodies | Not done | Yes 2 Feb 2022: (+) |
Not done | Not done | Not done | Not done | Not done | Not done | Not done | Not done | Not done |
| Health status | |||||||||||
| General health | Excellent | Good | Very good | Excellent | Excellent | Very good | Very good | Very good | Good | Very good | Good |
| Quality of life | Excellent | Excellent | Very good | Excellent | Excellent | Good | Very good | Excellent | Very good | Very good | Good |
| Physical health | Very good | Good | Very good | Very good | Excellent | Very good | Very good | Very good | Good | Very good | Good |
| Mental health | Excellent | Excellent | Very good | Good | Very good | Good | Very good | Excellent | Very good | Very good | Good |
| Satisfaction in social activities | Excellent | Excellent | Very good | Very good | Very good | Good | Very good | Excellent | Very good | Excellent | Good |
| Ability to perform social activities | Excellent | Good | Very good | Good | Excellent | Good | Very good | Excellent | Excellent | Very good | Excellent |
| During the seven days before the survey | |||||||||||
| Emotional problems | Never | Rarely | Rarely | Rarely | Rarely | Sometimes | Rarely | Never | Never | Rarely | Sometimes |
| Fatigue | Mild | Mild | Mild | Mild | Mild | Mild | None | Mild | None | Mild | Mild |
| VAS pain | 1 | 1 | 0 | 3 | 1 | 0 | 0 | 0 | 0 | 2 | 0 |
AZA: azathioprine; Covishield (Serum Institute of India); CYS-A: cyclosporine A; GC: glucocorticoid; HA: haemolytic anaemia; HCQ: hydroxychloroquine; ILD: interstitial lung disease; ITP: idiopathic thrombocytopenic purpura; MTX: methotrexate; Mo: Moderna; OxAZ: Oxford/Astra Zeneca; Pf: Pfizer-BioNTech; Sino: Sinovac-CoronaVac; Sp: Sputnik; SSZ: sulfasalazine; VAS: Visual Analogic Scale (0−10).
(a) Fever, muscles aches, cough, loss of smell, loss of taste, congestion, throat pain/scratchiness. No hospitalisation. No special treatments. Symptoms lasted for 12 days. SLE did not flare up after COVID-19 infection.
(b) Fever, loss of smell, loss of taste, running nose, congestion, throat pain/scratchiness. No hospitalisation. No special treatments. Symptoms lasted for 5 days. SLE did not flare up after COVID-19 infection.
(c) Fever, cough, running nose, congestion. No hospitalisation. No special treatments. Symptoms lasted for 4 days. Reported uncertainty regarding whether SLE flared up after COVID-19 infection.
(d) Fever, cough, fatigue, difficulty in breathing or shortness of breath, loss of smell, loss of taste, diarrhoea. No hospitalisation. No special treatments. SLE did not flare up after COVID-19 infection.
It is worth noting that none of the patients reported thrombotic events post-vaccination, which provides some reassurance regarding COVID-19 vaccination in a patient population with a high risk for cardiovascular comorbidity and thrombosis, especially in the presence of antiphospholipid antibodies or in patients diagnosed with the antiphospholipid syndrome, a considerable portion within SLE populations [7]. Moreover, it was reassuring to note an absence of association between experienced vaccine AEs and active disease prior to vaccination. Although minor AEs were common, they did not impair daily functioning, and the symptoms resolved in all patients after a median of 3 (IQR: 2.5–5.0) days.
Our report adds relevant evidence concerning the sensitive issue of COVID-19 vaccine AEs and flares in SLE patients during the antenatal and lactation period. Despite the small sample size, the findings provide some reassurance and can contribute to informed decisions regarding vaccination in patients with SLE and high-risk pregnancies due to their background autoimmune disease. Based on the present data, the risk/benefit ratio of COVID-19 vaccination appears favourable, with vaccines both providing passive immunisation to the fetus and active immunisation to the mother with no signals of exacerbation of the mother's autoimmune disease.
This study was not designed to ascertain causality. Further exploration in long-term prospective studies exploring AEs in the gestational and post-partum periods is necessary. Pregnant women with SLE who receive COVID-19 vaccines should be encouraged to report AEs. Alongside, it is crucial to be vigilant to widespread misinformation regarding the safety of COVID-19 vaccination in this group of patients.
Funding
I.P. is supported by grants from the Swedish Rheumatism Association (R-941095), King Gustaf V's 80-year Foundation (FAI-2020–0741), Professor Nanna Svartz Foundation (2020–00368), Swedish Society of Medicine (SLS-974449), Ulla and Roland Gustafsson Foundation (2021–26), Region Stockholm (FoUI-955483) and Karolinska Institutet.
CRediT authorship contribution statement
Nefeli Giannopoulou: Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing – original draft, Writing – review & editing. Latika Gupta: Conceptualization, Data curation, Investigation, Methodology, Software, Validation, Writing – review & editing. Laura Andreoli: Conceptualization, Data curation, Investigation, Methodology, Validation, Writing – original draft, Writing – review & editing. Daniele Lini: Data curation, Formal analysis, Investigation, Methodology, Validation, Writing – review & editing. Elena Nikiphorou: Conceptualization, Data curation, Investigation, Methodology, Validation, Writing – review & editing. Rohit Aggarwal: Data curation, Investigation, Methodology, Software, Validation, Writing – review & editing. Vikas Agarwal: Data curation, Investigation, Methodology, Software, Validation, Writing – review & editing. Ioannis Parodis: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Software, Validation, Writing – original draft, Writing – review & editing.
Declaration of Competing Interest
R.A. has a consultancy relationship with and/or has received research funding from Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Kyverna Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, Roivant, Merck, Galapagos, Actigraph, Scipher, Horizon Therapeutics, Teva, Beigene, ANI Pharmaceuticals, Biogen, Nuvig, Capella Bioscience, and CabalettaBio. I.P. has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis, and F. Hoffmann-La Roche AG. The other authors declare that they have no conflict of interest.
Acknowledgements
The authors are grateful to all respondents for completing the questionnaire. The authors also thank the Myositis Association, Myositis India, Myositis UK, Myositis Association of Australia, Myositis Support and Understanding, the Myositis Global Network, Deutsche Gesellschaft für Muskelkranke e. V. (DGM), Dutch and Swedish Myositis patient support groups, Cure JM, Cure IBM, Sjögren's India Foundation, Patients Engage, Scleroderma India, Lupus UK, Lupus Sweden, Emirates Arthritis Foundation, EULAR PARE, ArLAR research group, AAAA patient group, APLAR myositis special interest group, Thai Rheumatism association, PANLAR, AFLAR, NRAS, Anti-Synthetase Syndrome support group, and various other patient support groups and organizations for their contribution to the dissemination of this survey. Finally, the authors wish to thank all members of the COVAD study group (see supplementary material) for their invaluable role in the data collection.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.autrev.2023.103292.
Appendix A. Supplementary data
Supplementary material
Data availability
Data will be made available on request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary material
Data Availability Statement
Data will be made available on request.