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


From 1200 hospitalised patients due to SARS-CoV-2 infection from February 20 to May 31, 2020, a total of 369 (30.7%) reporting myalgia as a symptom during the acute phase of the infection and at hospital admission, and 369 age- and sex-matched patients without reporting myalgia during the acute phase of the disease were included. All were Caucasian. Figure 1 shows a flow diagram summarizing the hospitalization patients, the number of deaths at hospital and follow-up, and excluded patients.

Figure 1.

Flowchart showing of the number of patients throughout the study.

COVID-19–Related Symptoms at Hospital Admission

The most common symptoms at hospital admission due to COVID-19 infection were fever, dyspnoea, cough, and headache. Dyspnoea and cough were less frequent in patients presenting with myalgia (22.5% and 20.5%, compared with 38.5% and 27.5%, respectively, P < 0.01). No other significant differences in symptoms at onset were observed (Table 1). Almost 90% of patients reporting myalgia at hospital admission described this symptom as generalized muscle diffuse pain. Three hundred (40.5%) patients had no comorbidity, 393 (53.5%) had 1 or 2 comorbidities, and the remaining 45 (6%) reported ≥3 comorbidities. Patients reporting previous history of musculoskeletal pain were more prone to suffer from viral-induced myalgia at hospital admission (24% vs 15%, respectively; OR 1.79, 95% CI 1.23–2.60, P = 0.023). Neck and low back pain were the most prevalent preexisting musculoskeletal pain conditions reported by patients before infection, without differences between myalgia and nonmyalgia groups. Clinical and hospitalisation data of both groups are summarized in Table 1.

Post-COVID Symptoms

Participants were assessed a mean of 7.2 months (SD 0.6) after hospital discharge. At the time of the evaluation, only 257 (35%) were completely free of any post-COVID symptom, 357 (48.5%) had 1 or 2 symptoms, and the remaining 123 (16.5%) had 3 or more post-COVID symptoms. A significantly greater proportion (X2: 10.651, P = 0.03) of patients reporting viral-induced myalgia during the acute phase experienced ≥3 post-COVID symptoms when compared to those without viral-induced myalgia. However, no significant differences in the total number of general post-COVID symptoms (OR 1.09, 95% CI 0.98–1.20, P = 0.1) between individuals with (mean: 2.2, SD 1.5) and without (mean: 2.0, SD 1.4) myalgia at hospital admission were found.

Figure 2 graphs the distribution of the 6 most prevalent post-COVID symptoms in patients with and without myalgia during the acute phase of the disease at 7 months after hospitalisation. The most prevalent long-term post-COVID symptoms were fatigue, dyspnoea on exertion, musculoskeletal pain, dyspnoea at rest, hair loss, and memory loss. No significant differences in the presence of persistent fatigue (OR 1.05, 95% CI 0.77–1.42, P = 0.74), dyspnoea on exertion (OR 0.98, 95% CI 0.73–1.31, P = 0.88), or dyspnoea at rest (OR 0.83, 95% CI 0.59–1.17, P = 0.322) were found based on the presence or absence of myalgia at hospital admission (Table 2).

Figure 2.

Distribution of the most prevalent post-COVID symptoms (fatigue, dyspnoea on exertion, musculoskeletal pain, dyspnoea at rest, hair loss, and memory loss) in patients with and without viral-induced myalgia at the acute phase of infection.

A significantly greater proportion (OR 1.41 95% CI 1.04–1.904, P = 0.02) of patients suffering from myalgia at hospital admission developed musculoskeletal post-COVID pain (42.5%) as compared to those not reporting myalgia at hospital admission (34.5%). Overall, the prevalence of musculoskeletal post-COVID pain in the sample was 38.4% (n = 284/738). From 284 individuals suffering musculoskeletal post-COVID pain (Table 2), 143 (50.3%) reported preexisting history of musculoskeletal pain conditions. Among these, 76/143 (53.1%) patients suffering from preexisting musculoskeletal pain condition before infection experienced an increase of their symptoms in intensity (53%), extension (25%-27%), or frequency (17%-21%), without differences regarding the presence of myalgia at hospital admission (Table 2). Therefore, a total of 208 individuals (67/143 patients with preexisting musculoskeletal pain and 141 patients without a preexisting musculoskeletal pain) developed new-onset musculoskeletal post-COVID pain. Hence, the prevalence of new-onset post-COVID musculoskeletal pain was up to 73.2%. The location of persistent musculoskeletal post-COVID pain was similar in both groups, the spinal region being the most prevalent (Table 2).

No significant differences in HADS-A (P = 0.388), HADS-D (P = 0.825), and PSQI (P = 0.291) scores were observed between both groups. In fact, no significant association between the presence of myalgia at hospital admission with depressive symptoms (OR 1.06, 95% CI 0.72–1.55, P = 0.77), anxiety symptoms (OR 1.13, 95% CI 0.80–1.60, P = 0.479), and poor sleep quality (OR 1.02 95% CI 0.76–1.38, P = 0.770) was either found (Table 2).

The multivariate analysis revealed that after adjusting by all variables, individuals with viral-induced myalgia at the acute COVID-19 phase had a more frequent preexisting history of musculoskeletal pain conditions (OR 1.62, 95% CI 1.10–2.40, P = 0.015).