Safety of coronavirus disease 2019 vaccines in 213 adult patients with sickle cell disease

Summary

Given the lack of information about safety of the COVID‐19 vaccines for sickle cell disease (SCD) patients, we sought to determine whether COVID‐19 vaccine was associated with subsequent hospital admission for vaso‐occlusive events (VOEs). We included 402 patients with SCD, including 88 regularly transfused. As of July 31, 2021, 213 (53.0%) of them had received a least one dose of COVID vaccine (Pfizer 93.0%). We showed similar risk of hospital admission for a VOE among vaccinated patients (whether transfused or not) and among a control group of non‐vaccinated patients matched for age, sex and genotype.

Abbreviations

COVID‐19

coronavirus disease 2019

SCD

sickle cell disease

TP

transfusion program

VOEs

vaso‐occlusive events

INTRODUCTION

The coronavirus disease 2019 (COVID‐19) increases the risk of hospital admission in patients with sickle cell disease (SCD). Therefore, they constitute a high‐priority population for vaccination. ¹ Nevertheless, reactions like fever, myalgia and asthenia are common after vaccines, particularly after COVID‐19 vaccines. ² These effects are benign for the general population but might result in complications in people with SCD, which in turn might trigger painful vaso‐occlusive events (VOEs). ³ Alkindi et al. reported a safety warning for the ChAdOx1 nCov‐19 vaccine from Astra Zeneca in three patients with SCD. ⁴ One other case of hospitalization for a VOE and thrombocytopenia has been reported 4 days after BNT162b2 of Pfizer‐BioNTech in a 14‐year‐old teen. ⁵ In contrast, two recent studies reported good safety results for the AstraZeneca and Pfizer vaccines in relative small cohorts, and another reported adequate levels of neutralizing antibodies in 25 patients with SCD. ⁶ , ⁷ , ⁸

Given the lack of safety data on COVID‐19 vaccines in this at‐risk population, the primary objective of our study was to determine whether this vaccination was associated with subsequent hospital admission for a VOE. The study's secondary objectives were to determine the prevalence of vaccination in our cohort of SCD patients and to describe other adverse events associated with this vaccination.

PATIENTS AND METHODS

In accordance with the French guidelines on high‐priority populations, our referral center for adults with SCD started a vaccination campaign in March 2021. ⁹ Initially, we prioritized patients with SCD aged 45 or over and those with an SC genotype (the highest‐risk group). ¹ In May 2021, all patients with SCD aged 18 or over were invited for vaccination. During this period, the Pfizer vaccine was the most widely accessible in France and recommended in people <55 years because of an increased risk of thrombotic complications among younger populations with the Astra Zeneca vaccine. ¹⁰ Our SCD patients were informed about the necessity of vaccination at each appointment and by e‐mails (sent monthly from March 2021 onwards).

By screening the patients' electronic medical records, we retrospectively identified all individuals with SCD, having consulted at or been admitted to the day hospital unit in our centre between January 1 and July 31, 2021. We contacted them by phone or by email between 1 to 2 months after the vaccination. We recorded the type of vaccine, the vaccination dates, the number of injections, the occurrence of specific adverse events (fever, myalgia, etc.) and the occurrence of VOEs managed at home. Hospital admissions for a VOE were identified by screening with the ICD‐10 code D570 or by assessing the emergency department's registration form.

Non‐vaccinated patients followed up over the same period were contacted by phone or e‐mail after July 31, 2021, in order to confirm the absence of vaccination. Patients who did not reply were excluded.

All comparisons were performed separately in patients treated by regular transfusion (TP+ group) and those not (TP‐ group). In a matched case–control analysis, vaccinated patients were matched 1:1 for age (± 2 years), sex and SCD genotype with non‐vaccinated SCD patients. Hospital admissions (or emergency department visits) for a VOE within 21 days of the date of the first vaccination were compared with the controls. A self‐controlled case series analysis compared the same outcomes in vaccinated patients during the study period with the same period of the previous year.

The statistical analysis was performed using R software (V4.1.0) and its Matchit package. ⁹ McNemar test was used for comparisons.

Our analysis of de‐identified patient data was approved by a local institutional review board.

RESULTS

A total of 402 patients were included (314 in the TP‐ and 88 in the TP+ groups) (Figure S1). As of July 31, 2021, 213 of them (53.0%) had received a least one dose of COVID vaccine. The median [range] age of the vaccinated patients was 30 years [17–67] and 79% had the SS or Sß⁰ genotypes (Table 1). One‐hundred‐ninety‐eight patients had received the Pfizer‐BioNTech vaccine (93.0%), 8 the Moderna (3.8%) and 7 the Astra Zeneca (3.3%).

TABLE 1.

Characteristics of the study population

	All patients (n = 402)	Non vaccinated (n = 189)	Vaccinated (n = 213)	p value
Age (years), median [range]	29 [17–73]	27 [18–73]	30 [17–67]	0.03
Sex, n (%) (F)	231 (57.46)	106 (56.08)	125 (58.69)	0.67
Genotype, n (%)
SS	301 (74.88)	140 (74.07)	161 (75.59)	0.29
Sβ0	12 (2.99)	4 (2.12)	8 (3.76)
SC	69 (17.16)	32 (16.93)	37 (17.37)
Sβ+	17 (4.23)	12 (6.35)	5 (2.35)
Others	3 (0.74)	1 (0.53)	2 (0.93)
Treatment, n (%)
e Hydroxyurea	222 (55.22)	101 (53.44)	121 (56.81)	0.56
Crizanlizumab	5 (1.24)	1 (0.53)	4 (1.88)	0.38
Regular phlebotomy	14 (3.48)	5 (2.65)	9 (4.23)	0.56
Transfusion program	88 (21.89)	37 (19.58)	51 (23.94)	0.35
Hospitalization for VOE (1 year before inclusion), median [range]	0 [0–16]	0 [0–16]	0 [0–16]	0.16

In vaccinated patients, the most frequent side effects reported within 48 h of the first vaccine administration were muscle pain at the injection site (35.2%), asthenia (25.4%), body ache (16.9%), headache (14.6%) and fever (11.3%) (Figure S2).

Fourteen of the 213 vaccinated patients (6.6%) were hospitalized for a VOE (including 3 with ACS) within 3 weeks of the first dose (6.8% in the TP‐ group and 5.9% in the TP+ group; p = 1). In both the TP‐ and TP+ groups, the median [range] time interval between vaccination and hospital admission was 15 days [0–20]. Additionally, 8/162 patients (4.9%) in the TP‐ group and 1/51 (2%) in the TP+ group reported VOEs managed at home.

To assess the risk of a post‐vaccination VOE in the TP‐ group (n = 314), we studied 129 pairs matched for age, sex and genotype (Figure 1). Nine (7.3%) of the 129 vaccinated patients had been admitted to hospital for a VOE in the 21 days following their first injection, compared to 9 of the matched non‐vaccinated patients (7.3%) during the same period (p = 1). In the self‐controlled case‐series study, 10 (7.1%) of the 141 vaccinated patients had been hospitalized for a VOE within the 21 days of the first injection in 2021, whereas 8 had been hospitalized for a VOE (5.7%) during the same calendar period in 2020 (p = 0.53) (Figure 1).

FIGURE 1.

Prevalence of hospitalisations for a post‐vaccination vaso‐occlusive events within 21 days of the date of the vaccination in a matched case–control analysis (vaccinated patients matched with non‐vaccinated SCD patients at the same date of 2021) and a self‐controlled analysis (control is the same patient at the same date of the previous year‐2020). Group of patients treated by regular transfusion (Panel B) and those not (Panel A) are presented.

We next looked at whether hospital admission for a VOE in the 30 days before vaccination was a risk factor for a VOE after vaccination. In the matched case–control analysis, 8 of the 129 (6.2%) vaccinated patients had been hospitalized for a VOE in the 30 days before the first injection, and 11 (8.5%) of the non‐vaccinated patients had been admitted during the same period (p = 0.47) (Figure 1). In the self‐controlled case‐series analysis, 10 of the 141 vaccinated patients (7.1%) had been hospitalized for a VOE before the date of vaccination in 2021, whereas 5 (3.5%) had been hospitalized for a VOE during the same calendar period in 2020 (p = 0.17).

Comparative analyses for the TP+ group gave similar results than TP‐ group (Figure 1).

DISCUSSION

Our results demonstrate that the COVID‐19 vaccines have a good safety profile in adult patients with SCD. The observed adverse events were as expected, very similar to those observed in the general population. ² More importantly, the risk of hospital admission after vaccination was similar for patients with SCD (whether enrolled in a transfusion program or not) vs. a control group of non‐vaccinated patients with SCD matched for age, sex, genotype and disease severity. This conclusion was confirmed in a self‐controlled analysis, which took account of inter‐individual variability. Moreover, COVID‐19 vaccination during or after hospitalization for a VOE did not appear to be associated with a greater risk of a second hospital admission for a VOE after vaccination.

The literature data on the safety of various vaccines (against influenza, pneumococcal infections and yellow fever) in SCD children indicate that the risk of a VOE or hospital admission is not abnormally elevated; however, with the exception of one study, there are no published data for adult patients. ¹¹ , ¹² , ¹³ , ¹⁴ If the majority of these studies lacked control groups, Hambidge et al. found no evidence of a greater risk of hospital admission for a VOE after influenza vaccine compared to non‐vaccinated matched SCD children, but no details of VOEs managed at home were reported. ³ , ¹² Recently, Friedman et al. reported no increased risk of hospitalization after COVID‐19 vaccine in a self‐controlled study for 71 SCD patients in the week after injection comparatively with the risk of average hospitalization per week in 2019. ⁷ Of note, we observed vaccine reported fever in only 11.3% of our patients, which is similar to that reported by Jan et al with ARNm vaccines in SCD adult patients (16%), with no evidence of an elevated risk of admission in these individuals. ⁶

Our study had some limitations, including the retrospective design, the limited sample (which represent 5–8% of adult SCD patients living in the Paris area) and the predominant used of the Pfizer vaccine. Thus, we cannot rule out an association between the risk of hospital admission in patients with SCD having received another vaccine.

From the start of the vaccination campaign, we proactively and regularly informed patients. Despite our efforts, we failed to convince them. Indeed, the vaccination rate among our patients was lower than that recorded for the general population on July 31, 2021, particularly for the 18–39 age group (48.9% vs. 72.3%) (Supplemental Data Figure 3). ¹⁵ This difference was perhaps linked to mistrust of the vaccine promulgated over social networks. Studies in many countries have shown that the socio‐professional category, ethnicity, geographical origin and political affiliations can influence the level of vaccination. ¹⁶ However, a study of a population of patients with SCD in London found that vaccination uptake was around 80%, higher than among older people of African origin in general. ¹⁷

These safety results for COVID‐19 vaccines are reassuring and might help to promote vaccination among reluctant patients at a high risk of COVID‐19.

AUTHOR CONTRIBUTIONS

Laure Joseph and Jean‐Benoit Arlet designed the study. Anne Corbasson, Sandra Manceau and Djamal Khimoud collected the datas. Anne‐Sophie Jannot and Estelle Lu performed the analyses. Benoit Meunier, Geoffrey Cheminet and François Lefrere followed patients. All authors participated in data interpretation, revised the manuscript for critical content and approved the final manuscript.

FUNDING INFORMATION

NA.

CONFLICT OF INTEREST

The authors declare no competing financial interests.

PATIENT CONSENT STATEMENT

Patients were informed orally with a note of no objection.

PERMISSION TO REPRODUCE MATERIAL OTHER SOURCES

NA.

Supporting information

Table S1

Figure S1

Figure S2

Figure S3

Joseph L, Corbasson A, Manceau S, Khimoud D, Meunier B, Cheminet G, et al. Safety of coronavirus disease 2019 vaccines in 213 adult patients with sickle cell disease. Br J Haematol. 2022;00:1–5. 10.1111/bjh.18547

DATA AVAILABILITY STATEMENT

Data available on request due to privacy/ethical restrictions and data available in article supplementary material.