Post COVID-19 joint pain: Preliminary report of the relationship with antinuclear antibodies and inflammation.

INTRODUCTION

Post‐COVID syndrome includes a variety of symptoms after a SARS‐CoV2 infection. Close to 25% of the post‐COVID patients have muscle or joint pain and there are case series reporting a prevalence of up to 50% of antinuclear antibodies (ANAs) in acute critically ill COVID‐19 patients. Our aim is to present a preliminary comparison of post‐covid patients and their self‐reported joint and muscle pain, their inflammatory markers, and ANAs.

METHODS

We conducted a cross‐sectional study of the initial patients evaluated at our post‐COVID clinic. To be included in the post‐COVID clinic patients had to have a positive test for SARS‐CoV‐2 and have symptoms 3 months after the initial COVID‐19 diagnosis.

We collected post‐COVID symptoms using the CDC chronic fatigue symptom inventory as self‐reported by patients. The CDC inventory collects a battery of 22 symptoms and has been validated in chronic fatigue. We report the presence of joint pain, along with the frequency and severity, as well as the contribution of the symptom to feeling ill.

We report information on C‐reactive protein (CRP) and ANAs. ANAs were measured using immunofluorescence and for positive patients, we reported the pattern and the titer. We also collected if patients had a previous positive or negative screen. A positive ANA screen was defined as a positive test regardless of the pattern and titter.

RESULTS

We included the first 15 patients who enrolled in our post‐COVID clinic. Table 1 reports the baseline characteristics of the included patients. The majority of patients were female, belonged to a minority group, 20% were hospitalized for COVID‐19, 26% were healthcare workers and were seen in the post covid clinic around 7 months after the initial infection. Table 1 shows the entire cohort stratified by having a positive ANA screen. The prevalence of a positive ANA screen was 53% (95% confidence interval [CI]: 28–79). Those who had a positive ANA were more likely to be female, white, and more likely to be hospitalized. Five patients had a speckled ANA pattern and the others had a homogenous pattern. The median ANA titer was 120 (interquartile range [IQR]: 60–240). Three patients had a prior positive ANA and their median titer before COVID was 80 (IQR: 40–120), and in those three patients, the titer increased. None of the patients had a diagnosis of connective tissue disease and two patients had fibromyalgia. Patients with a positive ANA had a higher CRP compared with those with a negative ANA. Those who had a positive ANA screen presented earlier than those who had a negative screen. Figure 1 shows the association between the ANA and joint pain reported on the CDC inventory.

Table 1

Baseline characteristics

Characteristic	Entire cohort	ANA positive	ANA negative
Number	15	8	7
Age	52.6 ± 13.4	54.1 ± 7.4	51.2 ± 17.5
Female gender, %	53	63	43
Black race, %	40	25	57
Hispanic ethnicity, %	47	50	43
Healthcare worker, %	27	13	43
Number of days after the SARS‐CoV2 infection	200.6 ± 116.5	186.3 ± 80.5	217 ± 153.3
Hospitalized for COVID, %	20	25	14
Mean C‐reactive protein (SD)	2.8 (2.1)	3.1 (2.4)	2.5 (1.9)
Body mass index	29 ± 2.9	30 ± 1.6	28.2 ± 3.6
Depression, %	38	43	33
Hypertension, %	31	33	29
Hypothyroidism, %	23	33	14
Obstructive sleep apnea, %	31	67	0

Abbreviation: ANA, antinuclear antibody.

Figure 1

Association between joint pain and ANA screen in post COVID syndrome. ANA, antinuclear antibody

DISCUSSION

Our study shows a high prevalence of ANA positive screen with a high titer of antibodies in post‐COVID patients. We also found that patients with a positive ANA screen had more joint pain. Our main limitations are the small sample size and the cross‐sectional design.

Several manuscripts have documented an association between ANA and COVID‐19. , , ,  Two recent studies have documented the relationship between ANA and post‐COVID syndrome. In the first, Seesle et al. included 96 patients after 5 months after an acute COVID‐19 infection and found that after 12 months patients who had a positive ANA had more neurocognitive symptoms. The second, Peluso et al. reported 115 patients after 4–6 months of the initial infection and showed that only 3 out of 69 patients at 8 months had a positive ANA. Our study stands out in that we document the presence of ANA positivity in post‐COVID rather than acute disease. Furthermore, this high prevalence was documented in patients who had fairly mild COVID‐19.

Joint pain is common in post‐COVID patients and there are case reports of inflammatory arthritis in this group of patients. Our study contributes to this field as it associates post‐COVID syndrome with self‐reported joint pain and ANA positivity. There are several explanations for our findings. First, ANAs have been found in 5% of screened healthy adults. Second, ANAs are antibodies that bind to cellular components in the nucleus and autoimmunity has been proposed as a potential underlying etiology of post‐COVID. , ,

In conclusion, our study documents a high frequency of positive ANA screens in patients with post COVID syndrome and ta association between the positive screen with self‐reported joint pain. Future studies should evaluate the prognostic significance of this finding.

AUTHOR CONTRIBUTIONS

Study conception and design: Ana Palacio, Elizabeth Bast, Pat Caralis, Leonardo Tamariz, and Nancy Klimas. Data collection: Pat Caralis, Leonardo Tamariz, Maria Abad. Analysis: Leonardo Tamariz and Maria Abad. Interpretation of results: Elizabeth Bast, Ana Palacio, Leonardo Tamariz, Nancy Klimas, and Pat Caralis. Draft manuscript preparation: Maria Abad, Leonardo Tamariz, Ana Palacio, and Elizabeth Bast. Revision of the final draft: Nancy Klimas, Ana Palacio, Elizabeth Bast, and Pat Caralis.

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.