Diagnosing SARS-CoV-2 vaccination-related rhabdomyolysis requires the exclusion of all differential causes

Letter to the Editor,

We read with interest the article by Pucchio et al. about a 16-year-old male with rhabdomyolysis that appeared a few hours after the first dose of the BNT162b2 vaccine [1]. The patient manifested clinically with severe, progressive myalgia and cola-like urine with a maximum creatine-kinase (CK) value of 147,600 U/l on hospital day 2 [1]. The patient benefited from intravenous fluids and sodium bicarbonate and made a full recovery [1]. The study is appealing but raises concerns that warrant further discussion.

According to a literature review, more than the two pediatric patients with SARS-CoV-2 vaccination-associated rhabdomyolysis as described by Pucchio et al. [1] have been documented. In addition to the index patient and the 16-year-old female with rhabdomyolysis after the second BNT162b2 dose [1], several other pediatric and adult patients with SARS-CoV-2 vaccination-associated rhabdomyolysis have been noted in publications (Table 1). SARS-CoV-2 vaccination-related rhabdomyolysis was also reported in a 16-year-old female after the second BNT162b2 dose [2], in a 19-year-old male after receiving the Johnson and Johnson vaccine [3], and in a 16-year-old male after receiving the second dose of BNT162b2 (Table 1).

Table 1.

Pediatric and adult patients with SARS-CoV-2 vaccination-related rhabdomyolysis reported as per the end of 2022

Age	Sex	Dose	Brand	Max. CK (U/l)	Comorbidities	Reference
Pediatric cases
16	F	2	BPV	984,900	Heterozygote DYSF mutation	[Katz et al. 2022]
16	F	1	BPV	141,300	Asthma, previous COVID-19	[Pucchio et al. 2022]
16	F	2	BPV	Several 100	None	[Kim et al. 2023]
19	M	Nr	JJV	44,180	None	[Gelberegger et al. 2021]
16	M	2	BPV	71,339	None	[Sutcu et al. 2022]
Adult cases
80	M	2	MOV	6546	DM	[Mack etal. 2021]
81	M	1	BPV	7799	CHD, CVD, PF	[Elias et al. 2021]
21	M	1	BPV	22,000	Asthma	[Nassar et al. 2021]
28	F	1	MOV	17,959	None	[Faissner et al. 2022]
79	F	2	BPV	14,342	Vasculitis	[Hakroush et al. 2021]
30	F	2	MOV	203,088	Previous rhabdomyolysis, RYR1	[Salter et al. 2021]
37	M	1	BPV	150,000	None	[Al-Rasby et al. 2022]
85	F	2	MOV	> 14,000	CVD, asthma, rheumatoid arthritis	[Ajmera et al. 2021]
80	M	2	BPV	280,609	COPD, asthma, CHD, AHT	[Ruijters et al. 2022]
27	M	Nr	AZV	250,000	CPT-II deficiency	[Tan et al. 2021]
69	F	2	BPV	8394	DM, CHD, AHT, asthma, HLP	[Unger et al. 2022]
31	F	Nr	AdC68-S	15,000	None	[Kalekar et al. 2022]
68	M	1	AZV	793,280	None	[Cirillo et al. 2022]

AHT, arterial hypertension; BPV, BioNTech Pfizer vaccine; CHD, coronary heart disease; CVD, cerebrovascular disease; DM, diabetes; f, female; HLP, hyperlipidemia; JJV, Johnson and Johnson vaccine; m, male; MOV, Moderna vaccine; nr, not reported; PF, pulmonary fibrosis

The number of adult patients with SARS-CoV-2 vaccination-associated rhabdomyolysis is higher than presented in Table 1 of Pucchio’s article [1]. More than eight adult patients have been reported. When searching PubMed through the end of December 2022, five pediatric and at least 13 adult cases with SARS-CoV-2-associated rhabdomyolysis were collected (Table 1). Additionally, SARS-CoV-2-associated rhabdomyolysis has been reported to the vaccine adverse event reporting system (VAERS) in 20 cases through July 2021 [4]. Ten more cases have been reported to the Netherlands Pharmacovigilance Centre Lareb and 536 cases to VigiBase, the World Health Organization’s (WHO) global individual case safety report (ICSR) database [4]. A search of VAERS in November 2021 revealed 386 reported cases of COVID-19 vaccine-related rhabdomyolysis [7]. However, system limitations make the utility of the latter information problematic [5].

We also note that there are other causes of rhabdomyolysis that should be considered. In addition to trauma, excessive workout, immobility, illicit drug or alcohol use, or malignant neuroleptic syndrome, as mentioned in the introduction [1], rhabdomyolysis also can be due to medications, infections, vaccinations, snakebites, intoxications, malignant hyperthermia susceptibility (MHS), seizures, immunological disorders, and primary or secondary myopathy [6].

It would be interesting to know why the neurological examination was normal [1]. In a patient with rhabdomyolysis, one would expect fatigue, tiredness and exercise intolerance, muscle soreness, decreased tendon reflexes, pain with passive or voluntary movements, and even muscle weakness.

Because of the individual history positive for asthma, and because asthma attacks can be complicated by rhabdomyolysis, we should know whether the patient experienced an asthma attack shortly prior to onset of myalgia.

Overall, the interesting study carries some limitations that require re-evaluation and discussion. Clarifying these weaknesses would strengthen the conclusions and could make the study even more interesting. Before attributing rhabdomyolysis to a SARS-CoV-2 vaccination, all differential causes need to be thoroughly ruled out.

Author contribution

JF, design, literature search, discussion, first draft, critical comments, and final approval. FS, literature search, discussion, critical comments, and final approval.

Data availability

All data are available from the corresponding author.

Code availability

Not applicable.

Declarations

Ethics approval

Only secondary data were used.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Conflict of interest

The authors declare no competing interests.