COVID-19 vaccines associated with vasovagal malaise: A retrospective study in two mass vaccination centers and analysis of the WHO pharmacovigilance database

Figures & data

Table 1. Characteristics of vasovagal malaise events after receipt of COVID-19 vaccine (n = 408) at two mass vaccination sites (Caen, Normandy, France), January 18, 2021-October 15, 2021.

General characteristics	n = 408
Vasovagal malaise reporting date	19/05-04/10/21
Vaccine
Pfizer® [n (%)]	408 (100.0%)
Dose administred [n (%)]
First	319 (78.2%)
Second	89 (21.8%)
No. of syncope, cases* [n (%)]	97 (23.8%)
No. vaccinated, total	249,872
Cases per 1,000 vaccinated, total	1.63
Case characteristics
Women [n (%)]	213 (52.2%)
Men [n (%)]	195 (47.8%)
Age range, years [n (%)]
12–17	96 (23.5%)
18–29	193 (47.3%)
30–39	55 (13.5%)
40–49	40 (9.8%)
50–59	15 (3.7%)
60+	9 (2.2%)
Time delay after COVID-19 vaccination (min)	5.0 ± 4.2
Time delay to recovery (min)	40.8 ± 236.7
Transported to emergency department [n (%)]	6 (1.5%)
Reported history of anxiety related to needles or medical visits [n (%)]	232 (56.8%)
Reported anxiety of COVID-19 vaccination [n (%)]	213 (52.2%)
History of vasovagal malaise [n (%)]	233 (57.1%)
Characteristic vaccination site
Outside temperature (Celsius degrees)	22.8 ± 3.6
Common signs and symptoms
Chest pain [n (%)]	21 (5.1%)
Hypotension [n (%)]	6 (1.5%)
Light-headness or dizziness [n (%)]	333 (81.6%)
Nausea/vomiting [n (%)]	140 (34.3%)
Pallor or diaphoresis [n (%)]	322 (78.9%)
Seizure-like activity [n (%)]	99 (24.3%)
Tachycardia [n (%)]	15 (4.0%) [missing = 37]

*Vasovagal malaise was defined as any of the following occurring in a person during the 15- minute postvaccination observation period at one of the two sites reporting these events: tachycardia, hyperventilation, dyspnea, chest pain, paresthesia, light-headedness, hypotension, headache, pallor, or syncope. Persons with allergic-like symptoms and those who received diphenhydramine or epinephrine were excluded.

Figure 1. Flow chart of the descriptive study in two French mass vaccination centers.

Figure 2. Flow chart of the descriptive study in Vigibase® conducted on January 26^th, 2022.

Table 2. Demographic data of COVID-19 vaccines associated with vasovagal malaise in VigiBase®.

		Malaise^*1	Total	Age class available	<18	18–44	45–64	65–74	75+	Sex available	Men	Women	Death	Serious^*2	Hospitalization*^3	Life threatening* ^4
COVID-19 mRNA COVID-19 mRNA
Elasomeran – Moderna®		Malaise -	531,151: 89.8%	486,862: 98.8%	9,231: 96.1%	199,291: 88.0%	164,447: 88.5%	68,942: 92.9%	44,951: 92.9%	527,987: 89.8%	161,311 : 90.0%	366,676 : 89.7%	5,884: 89.2%	8,012: 44.2%	35,262: 88.6%	7513: 88.1%
		Malaise +	60,117: 10.2%	5,758: 1,2%	370: 3.9%	27,106: 12.0%	21,441: 11.5%	5,237: 7.1%	3,426: 7.1%	59,886: 10.2%	17,948: 10.0%	41,938: 10.3%	712: 10.8%	10,096: 55.8%	4,534: 11.4%	1,013: 11.9%
Tozinameran – Pfizer®		Malaise -	1,374,099: 89.4%	1,139,320: 88.9%	47,306: 83.7%	529,519: 87.9%	366,307: 90.1%	103,209: 90.7%	92,979: 91.3%	1,357,401 : 89.3%	411,258 : 89.7%	946,143 : 89.2%	21,344: 90.0%	317,824: 90.5%	123,073: 89.3%	26,953: 88.7%
		Malaise +	163,626: 10.6%	141,959: 11.1%	9,193: 16.3%	73,199: 12.1%	40,102: 9.9%	10,559: 9.3%	8,906: 8.7%	162,498: 10.7%	47,453: 10.3%	115,045 : 10.8%	2,381: 10.0%	33,485: 9.5%	14,715: 10.7%	3,434: 11.3%
COVID-19 Ad
ChAdOx1 – Astrazeneca®		Malaise -	631,758: 98.7%	57,824: 42.2%	1,708: 92.9%	243,645: 86.9%	235,733: 87.5%	70,937: 91.5%	26,217: 92.0%	616,462: 88.2%	191,478 : 90.7%	424,984 : 99.9%	4,168: 90.2%	210,665: 91.3%	30,561: 90.4%	8,885: 90.0%
		Malaise +	8,337: 1.3%	79,249: 57.8%	130: 7.1%	36,681: 13.1%	33,589: 12.5%	6,557: 8.5%	2,292: 8.0%	82,408: 11.8%	19,608: 9.3%	628: 0.1%	454: 9.8%	20,076: 8.7%	3,245: 9.6%	983: 10.0%
NRVV Ad26 – Janssen®		Malaise -	110,859: 83.3%	89,047: 81.3%	1,467: 96.8%	44,846: 76.6%	33,236: 84.7%	6,572: 93.4%	2,926: 91.9%	10,9816: 98.0%	49,821: 85.1%	59,995: 81.7%	2,458: 89.3%	21,003: 88.9%	9,905: 89.4%	2481: 87.7%
		Malaise +	22,161: 16.7%	20,509: 18.7%	49: 3.2%	13,717: 23.4%	6,019: 15.3%	467: 6.6%	257: 8.1%	2,211: 2.0%	8,706: 14.9%	13,404: 18.3%	293: 10.7%	2632: 11.1%	1,171: 10.6%	349: 12.3%
NRVV Ad26 – Sputnik® I		Malaise -	4,013: 96.5%	3,902: 96.5%	20: 100.0%	2,454: 96.5%	1,209: 96.5%	168: 97.1%	51: 94.4%	3,971: 96.5%	1,562: 97.2%	2,409: 96.0%	17: 85.0%	119: 87.5%	67: 90.5%	16: 88.9%
		Malaise +	146: 3.5%	142: 3.5%	0: 0.0%	90: 3.5%	44: 3.5%	5: 2.9%	3: 5.6%	145: 3.5%	45: 2.8%	100: 4.0%	3: 15.0%	17: 12.5%	7: 9.5%	2: 11.1%
NRVV Ad5 – Sputnik® II		Malaise -	4,269: 96.5%	4,164: 96.5%	19: 100.0%	2,584: 96.6%	1,314: 96.7%	189: 95.9%	58: 93.5%	4,226: 96.5%	1,612: 97.4%	2,614: 96.0%	20: 87.0%	151: 90.4%	94: 94.0%	19: 90.5%
		Malaise +	153: 3.5%	149: 3.5%	0: 0.0%	92: 3.4%	45: 3.3%	8: 4.1%	4: 6.5%	152: 3.5%	43: 2.6%	109: 4.0%	3: 13.0%	16: 9.6%	6: 6.0%	2: 9.5%
Others
HB02 – Sinopharm®		Malaise -	43,207: 92.2%	42,457: 92.1%	263: 92.3%	28,325: 91.3%	10,999: 93.4%	2,077: 96.6%	793: 95.0%	43,073: 92.2%	20,959: 93.7%	22,114: 90.8%	89: 83.2%	535: 88.7%	243: 89.3%	67: 89.3%
		Malaise +	3,678: 7.8%	3,631: 7.9%	22: 7.7%	2,711: 8.7%	782: 6.6%	74: 3.4%	42: 5.0%	3,669: 7.8%	1,417: 6.3%	2,252: 9.2%	18: 16.8%	68: 11.3%	29: 10.7%	8: 10.7%
CZ020 – Coronavac®		Malaise -	45,553: 94.0%	43,841: 93.9%	219: 92.8%	21,648: 92.6%	1,443: 69.1%	4594: 95.3%	295: 54.6%	4,519: 61.1%	19,115: 94.5%	26,075: 93.6%	2103: 92.2%	5467: 91.5%	2,446: 89.6%	339: 95.5%
		Malaise +	2,905: 6.0%	2,863: 6.1%	17: 7.2%	1,728: 7.4%	644: 30.9%	229: 4.7%	245: 45.4%	2,881: 38.9%	1,104: 5.5%	1,777: 6.4%	179: 7.8%	505: 8.5%	284: 10.4%	16: 4.5%
NIV-2020-770 – Covaxin®		Malaise -	16: 10.6%	1,591: 92.2%	7: 100.0%	1,036: 89.6%	375: 96.6%	66: 100.0%	107: 99.1%	1,598: 92.2%	755: 91.7%	843: 92.6%	80: 98.8%	146: 98.0%	58: 98.3%	1: 100.0%
		Malaise +	135: 89.4%	134: 7.8%	0: 0.0%	120: 10.4%	13: 3.4%	0: 0.0%	1: 0.9%	135: 7.8%	68: 8.3%	67: 7.4%	1: 1.2%	3: 2.0%	1: 1.7%	0: 0.0%

^*1: Malaise – are reports of adverse effects without malaise. Malaise + are reports of adverse effects including a malaise

^*2: seriousness criteria include among others caused/prolonged hospitalization^*3 and life threatening^*4 adverse effects

Table 3. Number of reports of COVID-19 vaccines associated adverse effects per country shared to VigiBase® during the period of the study in a list of eight countries.

	Number of reports per countries*^1
	France	USA	UK	PRC	RF	India	Philippines	Morocco
COVID-19 mRNA
Elasomeran – Moderna®	20,147	379,628	36,290	0	0	0	4,444	0
Tozinameran – Pfizer®	86,213	585,174	166,102	0	0	1	11,912	1,653
COVID-19 Ad
ChAdOx1 – Astrazeneca®	28,245	3	264,727	0	0	22,481	34,135	13,511
NRVV Ad26 – Janssen®	1,438	77,373	10	0	0	0	3,850	731
NRVV Ad26 or Ad5 Sputnik®	1	0	1	0	0	74	852	0
Others
HB02 – Sinopharm®	0	0	0	0	0	0	181	19,993
CZ02 – Coronavac®	0	0	0	0	0	0	32,336	0
NIV-2020-770 – Covaxin®	0	0	0	0	0	1,575	0	0
TOTAL
Total of COVID- 19 vaccines reports	136,615	1,044,118	464,636	3	0	24,136	87,314	36,314
Total reporting (including all drugs*^2)	207,441	2,241,045	565,736	264,345	0	74,757	91,016	37,441

aROR: adjusted reporting odds ratio; CI: confidence interval

Multivariate analysis: results were adjusted on age class, sex, region and qualification of reporter. Analysis population: reports with COVID-19 vaccines from 01/01/2021 to 26/01/2022 (reference: Influenza vaccines)

*¹: In rare cases, reporting is not precise enough to identify a specific vaccine (i.e., “COVID-19 vaccine mRNA S”)

*²: not restricted to covid-19 vaccines

USA: United States of America UK: United Kingdom PRC: People’s Republic of China RF: Russian Federation