Abbreviations
- COVID
coronavirus disease
- SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
Among the anti COVID-19 vaccine arsenal, ChAdOx1 nCov-19 vaccine relies on a replication-deficient chimpanzee adenovirus vector containing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) structural surface spike glycoprotein. The vaccine, administered as two intramuscular injections with a 4–12 week interval, has been approved in the UK on 30 December 2020, and across the European union on 29 January 2021 [1], [2]. Safety and efficacy have been demonstrated across four clinical trials among adult population [3], [4]. In an interim analysis, adverse events and especially serious ones were balanced between groups. Among the vaccinated population, authors report two cases of transverse myelitis, including one possibly related to the vaccine, and one case of high fever (above 40 °C) that recovered spontaneously [3]. However, local and systemic transient reactogenicity was very common, with fatigue reported in more than 50% of participants, and headache and malaise in up to 40% [5]. In the European product information, the most frequently noted symptoms included injection site tenderness or pain (respectively 64 and 54%), headache (53%), fatigue (53%), myalgia (44%), pyrexia [including feverishness (34%) and fever >38 °C (8%)], chills (32%) and arthralgia (26%) [2]. We report here our preliminary experience on the first days of healthcare workers massive immunization in a University hospital with ChAdOx1 nCov-19 vaccine.
We implemented the vaccination of healthcare professionals with ChAdOx1 nCov-19 vaccine in our 903-bed University hospital on 9th February 2021. All vaccinated healthcare professionals have been contacted by phone the third day after receiving the vaccine. Among the 68 persons (median age 34 [IQR 29–42] years) who were first vaccinated (batch number ABV 3025, expiration date May 2021), 54 (79%) reported adverse reactions compatible with systemic reactogenicity (Table 1 ). Typical presentation consisted in severe flu-like syndrome lasting from 1 to 3 days. Importantly, 32 professionals (47%) reported more than three different marked symptoms, that led to sick leave in 25 (37%). Seven reported fever ≥ 39 °C (10%) and two reported hallucinations/delirium. None required in-hospital management. No association with sex, medical history, or previous report of COVID-19 and reactogenicity severity was found. Since the implementation of the ChAdOx1 nCov-19 vaccine in France, similar observations were reported across the country to the French Pharmacovigilance Network [6]. These observations lead the French Medicines Agency to raise a possible safety signal shared with the European Medicine Agency [7]. This possible safety signal does not alter the very substantial benefit-risk balance of the ChAdOx1 nCov-19 vaccine ).
Table 1.
Cohort presentation.
| Vaccinated professionals (N = 68) | Vaccinated professionals without adverse reactions (N = 14) | Vaccinated professionals with adverse reactions (N = 54) | |||
|---|---|---|---|---|---|
| Overall (N = 54) | Adverse reactions leading to sick leave (N = 25) | Adverse reactions without sick leave (N = 29) | |||
| Median age–years | 34 | 34 | 34 | 34 | 34 |
| [Interquartile range] | [29–42] | [29–42] | [29–42] | [28–41] | [29–42] |
| Sex male: female | 22:46 | 4:10 | 18:36 | 10:15 | 8:21 |
| Comorbidities (N =) | |||||
| None | 59/68 (87%) | 10/14 (71%) | 49/54 (91%) | 22/25 (88%) | 27/29 (93%) |
| 1 | 7/68 (12%) | 3/14 (21%)a | 4/54 (9%)b | 3/25 (16%)c | 1/29 (3%)d |
| 2+ | 2/68 (3%) | 1/14 (7%)a | 1/54 (2%)b | 0c | 1/29 (3%)d |
| Past history of COVID-19 | 6/68 (9%) | 0 | 6/54 (11%) | 2/25 (8%) | 4/29 (14%) |
| Systemic reactogenicity | |||||
| Systemic symptoms–n | 53/68 (78%) | 53/54 (98%) | 23/25 (92%) | 29/29 (100%) | |
| No symptom | 3/68 (4%) | 3/54 (6%)h | 2/25 (8%)h | 1/29 (3%)h | |
| 1 symptom | 11/68 (16%) | 11/54 (20%) | 3/25 (12%) | 8/29 (28%) | |
| 2 symptoms | 8/68 (12%) | 8/54 (15%) | 7/25 (28%) | 1/29 (3%) | |
| 3+ symptoms | 32/68 (47%) | 32/54 (59%) | 13/25 (52%) | 19/29 (66%) | |
| Type of symptoms–ng | |||||
| Fever | 32/68 (47%) | 32/54 (59%) | 18/25 (72%) | 14/29 (48%) | |
| Fatigue | 27/68 (40%) | 27/54 (50%) | 11/25 (44%) | 16/29 (55%) | |
| Headache | 18/68 (26%) | 18/54 (33%) | 6/25 (24%) | 12/29 (41%) | |
| Myalgia/arthralgia | 34/68 (50%) | 34/54 (63%) | 16/25 (64%) | 18/29 (62%) | |
| Chills | 31/68 (46%) | 31/54 (57%) | 16/25 (64%) | 15/29 (52%) | |
| Othere | 5/68 (7%) | 5/54 (9%) | 4/25 (16%) | 1/29 (38%) | |
| Duration | |||||
| One day | 31/68 (46% | 31/54 (57%) | 12/25 (48%) | 19/29 (66%) | |
| Two days | 19/68 (28%) | 19/54 (35%) | 10/25 (40%) | 9/29 (31%) | |
| Three days | 3/68 (4%) | 3/54 (6%) | 3/25 (12%) | 0 | |
| Local reactogenicityf (N =) | 10/68 (15%) | 10/54 (19%) | 4/25 (16%) | 6/29 (21%) | |
Data are presented as median [interquartile range] or n (%). COVID-19: coronavirus disease 2019.
Comorbidities included: type 2 diabetes (N = 2), and hypertension, cardiac disease, and pituitary adenoma (N = 1, each).
Comorbidities included: hypothyroidism (N = 2), including one with obesity, hypertension, past history of preeclampsia, asthma (N = 1, each).
Comorbidities included: hypertension, past history of preeclampsia, and asthma (N = 1, each).
Comorbidities included: hypothyroidism (N = 2), including one with obesity (N = 1, each).
Other symptoms included tachycardia, paresthesia, neck stiffness, hallucinations and dizziness (N = 1, each).
Local reactogenicity consisted in local pain or erythema at injection site.
Total number of symptoms exceeds total number of patients.
These professionals have only local reactogenicity symptoms.
While vaccination is central instrumental to control the SARS-CoV-2 pandemic, this report highlights that the reactogenicity profile of the vaccine should be part of the equation when implementing large scale vaccination of healthcare professionals. Unlike mRNA vaccines, local reactions were not very common in our study [8]. Hence, local reactions were reported in up to 75.2% in mRNA vaccinated and in only 15% of our healthcare worker cohort vaccinated with the ChAdOx1 nCov-19 vaccine. On the opposite, systemic reactions were more frequent in our cohort. For instance, fever was reported in 47% of the healthcare workers receiving the vaccine, compared to 8.6% with a first dose of mRNA vaccine, in a population-based study [8]. Foremost, in our cohort, such systemic reactogenicity led to sick leave in more than one third of the vaccinated. This issue should be taken into account to address the paramount needing of rapidly protecting our professionals while maintaining the operation of high-demand services as the pandemic continues to unfold.
Contributors
LC and CC designed the study, performed statistical analysis and drafted the paper. EC and ACo collected the data. RB, ACa and JMT critically reviewed the paper. All the authors approved the final version of the paper. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Disclosure of interests
The authors declare that they have no competing interests.
Ethical approval
This research was found to be in conformity with the French regulations by the local Ethical Review Committee and has been approved under the number 2021-08009. In line with the French law, these individual case safety reports have been reported anonymously to the National Pharmacovigilance Database.
Acknowledgments
The authors would like to thanks to all the healthcare workers and the French Pharmacovigilance Network involved in large immunization campaign and in its safety monitoring [6].
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