Myalgia As a Symptom at Hospital Admission by Severe Acute Respiratory Syndrome Coronavirus 2 Infection Is Associated With Persistent Musculoskeletal Pain as Long-term Post-COVID Sequelae

A Case-control Study

César Fernández-de-las-Peñas; Jorge Rodríguez-Jiménez; Stella Fuensalida-Novo; María Palacios-Ceñ; Víctor Gómez-Mayordomo; Lidiane L. Florencio; Valentín Hernández-Barrera; Lars Arendt-Nielsen


Pain. 2021;162(12):2832-2840. 

In This Article

Abstract and Introduction


This study investigated the association between COVID-related myalgia experienced by patients at hospital admission and the presence of post-COVID symptoms. A case-control study including patients hospitalised due to COVID-19 between February 20 and May 31, 2020, was conducted. Patients reporting myalgia and patients without myalgia at hospital admission were scheduled for a telephone interview 7 months after hospital discharge. Hospitalisation and clinical data were collected from medical records. A list of post-COVID symptoms with attention to musculoskeletal pain was evaluated. Anxiety and depressive symptoms, and sleep quality were likewise assessed. From a total of 1200 hospitalised patients with COVID-19, 369 with and 369 without myalgia at hospital admission were assessed 7.2 months (SD 0.6) after hospital discharge. A greater proportion (P = 0.03) of patients with myalgia at hospital admission (20%) showed ≥3 post-COVID symptoms when compared with individuals without myalgia (13%). A higher proportion of patients presenting myalgia (odds Rratio 1.41, 95% confidence interval 1.04–1.90) exhibited musculoskeletal post-COVID pain when compared to those without myalgia. The prevalence of musculoskeletal post-COVID pain in the total sample was 38%. Fifty percent of individuals with preexisting musculoskeletal pain experienced a worsening of their symptoms after COVID-19. No differences in fatigue, dyspnoea, anxiety/depressive levels, or sleep quality were observed between myalgia and nonmyalgia groups. The presence of myalgia at hospital admission was associated with preexisting history of musculoskeletal pain (OR 1.62, 95% confidence interval 1.10–2.40). In conclusion, myalgia at the acute phase was associated with musculoskeletal pain as long-term post-COVID sequelae. In addition, half of the patients with preexisting pain conditions experienced a persistent exacerbation of their previous syndromes.


Patients affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can present with heterogeneous respiratory (dyspnoea and cough), gastrointestinal (diarrhea and vomiting), or neurological (headache and anosmia) symptoms.[18] In addition, the presence of generalised myalgia (viral-induced myalgia) is also a common symptom of the acute phase of coronavirus 2, 2019 disease (COVID-19).[41] The World Health Organization (WHO) recognized that 15% of patients with COVID-19 experience viral-induced myalgia as an associated symptom.[43] Two meta-analyses have also shown that myalgia has a pooled prevalence of 19% as a symptom during the acute phase of the infection.[1,11] In fact, myalgia and arthralgia are the fifth most prevalent symptoms during the COVID-19 acute phase.[42] The presence of myalgia at the acute phase has so far not been associated with worse prognosis,[38] disease severity,[30] or mortality.[29] However, Zhang et al.[44] found that myalgia was a predictive factor for the severity of the overall disease in individuals with abnormal computed tomographic or radiographic imaging of the lungs.

Due to the COVID-19 outbreak, an increase in the incidence of musculoskeletal pain could be expected, either by increasing the number of people developing new onset chronic pain as a result of COVID-19, or by an exacerbation of preexisting pain.[12] An increase in the severity of symptoms of chronic musculoskeletal pain conditions has been observed during the COVID-19 lockdown.[24,39] Importantly, in the face of a second pandemic due to COVID-19 sequelae, the characteristics of pain in "long-haulers"[37] need to be better investigated and understood to ensure proper approach among healthcare professionals. Evidence suggests that around 75% of previously hospitalised patients with COVID-19 can exhibit post-COVID symptoms; however, specific data on pain are scarce.[32] Furthermore, the prevalence rates of this symptom are heterogeneous depending on the follow-up period: 50% of persistent pain one month after the acute infection,[26] 15% two months after,[9] 25% three months after,[5] and 3% at 6 months since the infection.[25] Musculoskeletal pain during the acute infection by SARS-CoV-2 translates a heterogeneous pathophysiological process of COVID-19.[31] It is uncertain whether these mechanisms may contribute to post-COVID pain sequelae.

The aims of this study were to investigate (1) whether the presence of myalgia at hospital admission during the acute phase could be associated with the development of long-term post-COVID pain, and (2) whether previous musculoskeletal pain may worsen after COVID-19. We hypothesized that the presence of myalgia as a symptom during the SARS-CoV-2 infection might be a predictor for the development of persistent post-COVID pain at long term and exacerbate preexistence musculoskeletal pain problems.