|
| |
| ORIGINAL ARTICLE |
|
| Ahead of print publication |
|
|
Long COVID in patients with rheumatologic disease: A single center observational study
Horacio Quinones-Moya1, Armando Ocampo-Del Valle2, Adolfo Camargo-Coronel1, Francisco Javier Jimenenez-Balderas1, Miriam Berenice Bernal-Enriquez1, Pedro Madinabeitia-Rodríguez1, Kenia Nahomi Morales-Medino1, Cynthia Roque Ibanez1, Mario Raul Hernandez-Zavala1
1 Department of Rheumatology, Centro Médico Nacional Siglo XXI, Ciudad de México, México
2 Biotechnology Institute, Universidad Nacional Autónoma de México, Ciudad de México, México
| Date of Submission | 08-Jun-2022 |
| Date of Acceptance | 28-Aug-2022 |
| Date of Web Publication | 23-Nov-2022 |
Correspondence Address:
Horacio Quinones-Moya,
Department of Rheumatology, Centro Médico Nacional Siglo XXI, Ciudad De México
México
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/injr.injr_118_22
Background: Special attention has been paid to the sequelae caused by SARS-CoV 2 infection (Long-COVID), the prevalence of these sequelae in patients with rheumatological diseases has not been studied in detail. As these patients have immunosuppressive therapy and this syndrome has inflammatory characteristics, we postulate that these patients will have a lower prevalence of sequelae.
Methods: We conducted a retrospective, cross-sectional, single-center study in which we interrogated all the patients who had the diagnosis of rheumatological diseases who attended our hospital between August 1, 2021 and November 30 and who had a history of 3 or more months of SARS CoV2 infection. The interrogation consisted of a brief questionnaire on the persistence of symptoms 3 months after the event.
Results: We included 64 patients: 19 patients with rheumatoid arthritis (RA), 21 patients with systemic lupus erythematosus (SLE), and 24 with other rheumatological diseases. Long COVID symptoms reported were similar to those described in the literature of patients without rheumatic diseases. The prevalence of fatigue was significantly lower in SLE compared to RA and the rest of the pathologies, but there were no other significant differences between them.
Conclusions: The long COVID syndrome is common in patients with and without rheumatic diseases, and the prevalence of each of these symptoms differs little between these groups. A lower prevalence of post-COVID symptoms was seen in patients with SLE than in the rest of the rheumatological diseases, but after we run a binary logistic regression model, most of these differences were not significant and they did not differ much from the general population.
Keywords: Long COVID, lupus, post-COVID syndrome, rheumatologic
How to cite this URL:
Quinones-Moya H, Valle AO, Camargo-Coronel A, Jimenenez-Balderas FJ, Bernal-Enriquez MB, Madinabeitia-Rodríguez P, Morales-Medino KN, Ibanez CR, Hernandez-Zavala MR. Long COVID in patients with rheumatologic disease: A single center observational study. Indian J Rheumatol [Epub ahead of print] [cited 2023 Jan 30]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=361857 |
| Introduction | |  |
COVID-19 is an infectious disease identified for the first time in December of 2019 in China, by July 4 of 2021, more than 183,000,000 infected cases and more than 4,000,000 deaths had been reported.[1] As is implied by the name, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes acute respiratory illness, this is why when several patients began to report the persistence of some symptoms, not related to the respiratory system, long after the acute infection process, the majority of the medical community dismissed such claims in a phenomenon known as “medical gaslighting;” this is a phenomenon in which the physician denies the existence of the patient's symptoms or attributes them to anxiety or depression.[2] Despite this, the evidence of sequelae due to COVID-19 has continued to accumulate, which is why several terms have been created to classify these patients: “prolonged COVID,” “post-COVID syndrome,” “chronic COVID syndrome,” etc.[1],[3]
In [Supplementary Table 1], we describe some proposed terms being one of the most used terms “long COVID,” this term was first used in social networks by patients who had persistent symptoms even several months after the acute infection[4] finally being accepted by the medical community as a new clinical entity.[3],[5]
Since this syndrome was described, multiple observational studies have been carried out on patients surviving COVID-19[6],[7],[8],[9],[10] all these studies with very different characteristics (samples from 22 to 4182 patients and with a follow-up of 3–6 months) and with highly variable results (prevalence of symptoms from 40% to 90%).[11] These discordant results can be attributed to the fact that their study populations are not homogeneous and more specific analyses of subgroups were not carried out.
Pathophysiology
There is still no specific explanation for why COVID-19 could leave long-term symptoms, SARS-CoV-2 is a virus whose route of entry into the body is the upper respiratory tract and whose main manifestations are respiratory.[12] One explanation for why it would have short- and long-term effects on various devices and systems is that this virus is internalized in the cell by binding to the receptor for angiotensin-converting enzyme type 2,[13] and these receptors have been found in the lungs, heart, kidneys, spleen, gastrointestinal tract, liver, vascular endothelium, etc.;[14] once internalized, the virus begins its replication, which causes the activation of the immune system, migration and invasion of leukocytes, and release of abundant cytokines;[1] this will cause inflammation and therefore dysfunction of the affected tissues.
At the beginning of this pandemic, it was postulated that the immunosuppressive therapy received by patients with rheumatological diseases could reduce the cytokine storm that occurs in COVID-19 and therefore reduce mortality.[15],[16] This was partially disproved a few months later with the arrival of large randomized trials[17],[18] and partially confirmed by others,[19],[20],[21] being tocilizumab and dexamethasone the main current therapies for the treatment of COVID with oxygen requirement from what we consider it is possible that immunosuppressive therapy decreases the impact of COVID-19 on the body.
However, little is really known about the effect that this pandemic had and will have on patients with immunosuppressive therapies, so we decided to carry out a observational study to evaluate the long-term effect of COVID-19 on patients with rheumatological diseases.
| Methods | | |
This was an observational, retrospective, cross-sectional, single-center study. It was done in the hospital “Centro Médico Nacional Siglo XXI” which is a tertiary care hospital located in the center of the country and is one of the main reference hospitals nationwide in Mexico. Study was approved by CONBIOETICA 09 CEI 0232017082.
To be included, patients must be over 18 years of age, have a diagnosis of some established rheumatic disease, have had a confirmed symptomatic infection of SARS-CoV-2 by any laboratory test (polymerase chain reaction, viral antigen test, or positive antibodies after an event acute) and at least 3 months after the acute infectious event. All patients without a definite diagnosis of rheumatological disease, under 18 years of age, with a diagnosis of fibromyalgia (this was because long COVID symptoms closely resemble those of fibromyalgia),[22] <3 months after the infectious event or those without laboratory tests that confirmed said infectious event were excluded.
All patients who attended the rheumatology outpatient clinic in a period of 3 months (October 1 to November 30, 2021) were questioned about the history of symptomatic infection by SARS-CoV-2 confirmed by laboratory tests, in case if they referred said event, they were given a brief questionnaire on residual symptomatology, the characteristics of the patient and their underlying rheumatologic disease, clinical characteristics of the infectious process, and if the infection modified in any way his rheumatological disease.
The following complications were evaluated: anosmia, fatigue, myalgia, arthralgia, palpitations, ageusia, exanthema, headache, depression, alopecia, dyspnea, attention disorders, or others. We also questioned if, according to the patient's own criteria, his rheumatological disease had worsened, improved, or had remained unchanged after the infectious event. The data collected were stored electronically.
Initially, it was planned to analyze the prevalence of the post-COVID syndrome and its characteristics in each of the rheumatological diseases, but due to the rare nature of rheumatological diseases, the sample size obtained was small, so it was decided to subdivide the sample into three groups: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and miscellaneous. In this last group, all rheumatic diseases that did not reach a sample number >10 were included.
When capturing the patients, they were questioned in a directed manner about the presence of the most reported symptoms in the medical literature, the symptoms should have started at the time of corroborating the SARS CoV2 infection through laboratory tests, in case they had been present in a regular way, prior to the infection, they were only taken as positive if these symptoms were exacerbated after the infection, in addition, they had to persist at the time of the interrogation.
The information collection was carried out through the clinical record. From which information such as age, sex, date of diagnosis, admission to hospitalization, and use of supplemental oxygen was extracted. Together to evaluate the recovery and the presence of post-COVID complications, a medical examination of the patients was carried out. The glm package (v 3.6.2) was applied to run a binary logistic regression model to evaluate the influence of complications in long COVID syndrome and its association in patients with lupus erythematosus and arthritis patients by calculating relative risk (RR). The model was adjusted to age and gender. Results are presented as RR with corresponding 95% confidence intervals (CIs) with statistical significance levels set to 0.05, P value, and z score. The plots were generated by the ggplot2 package (v 3.3.5). Finally, the statistical analysis was performed by the R software version 4.2.1.
For the analysis of post-COVID complications in rheumatoid patients, univariate descriptive statistics were performed. Complications were taken as categorical variables from their presence or absence in the study groups, allowing for evaluating the frequency of presentation during the assessment.
| Results | | |
We interviewed a total of 64 patients: 21 with SLE, 19 with RA, 7 patients with systemic sclerosis (SSc), 4 patients with axial spondyloarthropathies, 3 patients with Sjogren syndrome, 3 patients with granulomatosis with polyangiitis (GPA), 2 patients with antiphospholipid antibody syndrome, 1 patient with juvenile idiopathic arthritis, 1 patient with adult-onset Still disease, 1 patient with psoriasis arthritis and 1 patient with dermatomyositis.
Most of our patients were women (76.56%), did not require supplemental oxygen (68.19%), and did not require hospitalization (90.63%). The rest of the demographics and clinical characteristics of the infectious process of each group are described in [Table 1]. | Table 1: Characteristics of the patients analyzed and characteristics of the acute infectious process
Click here to view |
Many of our patients, 62.5% (40/64), reported not having noticed any change in their disease after the infectious process; a third of the patients, 34.38% (22/64), reported worsening of their rheumatological disease; and a small part 1.32% (2/64) reported an improvement in their underlying rheumatic disease.
Fifty (78%) of the analyzed patients reported persistence of symptoms after 3 months of the acute infectious event. The prevalence of long COVID similar among the 3 groups: 15 of 21 patients (71.4%) in the SLE group, 15 of 19 patients (78.9%) for the RA group, and 20 of 24 patients (83.3%) for the miscellaneous group, with a close number of symptoms present at the time of the interrogation: 4.2, 5.7, and 5.4 respectively [Table 2]. | Table 2: Patients with persistence of symptoms after the acute infectious process and frequency of these symptoms
Click here to view |
The three most common symptoms reported by group were fatigue (33%), hair loss (28%), and sleep disturbances (28%) for SLE; fatigue (63%), headache (47%), and muscular weakness (42%) for RA; and fatigue (58%), arthralgias (45%), and palpitations (37%) for miscellaneous.
The frequency of symptoms was compared between each group, finding a lower prevalence of most of these symptoms in SLE compared to the other 2 groups [Table 3] and [Table 4]. | Table 3: Comparison of the prevalence of symptoms between systemic lupus erythematosus and rheumatoid arthritis
Click here to view |
 | Table 4: Comparison of the prevalence of symptoms between systemic lupus erythematosus and miscellaneous
Click here to view |
The RR of presenting manifestations in the long COVID syndrome is shown comparing patients with SLE and RA [Table 3] and [Figure 1]. The univariate analysis of fatigue (the most common symptom) as post-COVID sequelae in rheumatoid patients describes a lower number of cases in SLE patients (33%) compared to patients with RA (63%) or miscellaneous diseases (58%). The results obtained describe that there is a lower risk of presenting fatigue with a RR of 0.55 (95% CI: 0.44–0.69) in patients with SLE when compared to RA and a RR of 0.57 (95% CI: 0.44–0.73) when compared to miscellaneous (P = 0.02 and P = 0.046, respectively). | Figure 1: Comparison of risk of developing sequels in the long COVID syndrome in lupus erythematosus patients and rheumatoid arthritis patients
Click here to view |
We also found a lower risk of developing arthralgias in SLE patients when compared to the miscellaneous group [Table 4] and [Figure 2] with a RR of 0.47 (95% CI: 0.31–0.7); there were no other statistically significant differences. | Figure 2: Comparison of risk of developing sequels in the long COVID syndrome in lupus erythematosus patients and miscellaneous patients
Click here to view |
| Discussion | | |
Our study found a high prevalence of post-COVID syndrome in patients with rheumatic diseases, with few differences between the analyzed groups. We note that even though over 30% of the patients included in the study required the use of supplemental oxygen, only 10% received hospital care, the reason for this was not investigated.
As has already been reported in recent literature, SARS-CoV-2 infection has been related to the appearance of rheumatic diseases,[23] in this study, at least 3 previous healthy patients started with rheumatologic symptoms after the infectious process and were subsequently diagnosed with a rheumatologic disease (1 PM, 1 SLE, and 1 GPA).
The prevalence of post-COVID syndrome has been reported in very different proportions through several observational studies, but there are few who have described the presence of this syndrome in patients with rheumatic diseases.[24] Our study had multiple limitations; the total sample size and for each disease was small, there were considerable differences in the baseline characteristics of the patients belonging to each group, the time elapsed between the interrogation and the infectious process was very variable, and an analysis of the treatments received during the acute infectious process or of their rheumatological disease was not carried out.
Overall, patients with SLE presented a lower prevalence of most symptoms compared to RA and the miscellaneous group, but as mentioned above, most were not statistically significant.
As reported in a previously published meta-analysis of the prevalence and characteristics of post-COVID symptoms,[25] the prevalence of these symptoms after the infectious event does not differ between patients with or without rheumatological diseases when compared with our results (presence of post-COVID syndrome: 80% vs. 78%, fatigue: 58% vs. 52%, headache: 44% vs. 34.4%, hair loss: 25% vs. 21.9%, etc.).
| Conclusions | | |
The prevalence of post-COVID syndrome reported in our study did not differ from that reported in the meta-analysis by Lopez-León et al.,[23] the main symptoms reported were the same and their prevalence was similar, so we can conclude that the post-COVID syndrome presents in a very similar way in patients with rheumatological diseases to patients without these conditions. A lower prevalence of fatigue, but not other of these symptoms, was found in patients with SLE compared to RA. Larger studies are required to confirm these findings.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
[27]
| References | | |
| 1. | Crook H, Raza S, Nowell J, Young M, Edison P. Long covid-mechanisms, risk factors, and management. BMJ 2021;374:n1648.  |
| 2. | Yong SJ. Long COVID or post-COVID-19 syndrome: Putative pathophysiology, risk factors, and treatments. Infect Dis (Lond) 2021;53:737-54. |
| 3. | Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV, WHO Clinical Case Definition Working Group on Post-COVID-19 Condition. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis 2022;22:e102-7. |
| 4. | Raveendran AV, Jayadevan R, Sashidharan S. Long COVID: An overview. Diabetes Metab Syndr. 2021;15:869-75. doi: 10.1016/j.dsx.2021.04.007. Epub 2021 Apr 20. Erratum in: Diabetes Metab Syndr. 2022 May;16(5):102504. |
| 5. | Fernández-de-Las-Peñas C, Palacios-Ceña D, Gómez-Mayordomo V, Cuadrado ML, Florencio LL. Defining post-COVID symptoms (Post-Acute COVID, long COVID, persistent post-COVID): An integrative classification. Int J Environ Res Public Health 2021;18:2621. |
| 6. | Arnold DT, Hamilton FW, Milne A, Morley AJ, Viner J, Attwood M, et al. Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: Results from a prospective UK cohort. Thorax 2021;76:399-401. |
| 7. | Bellan M, Soddu D, Balbo PE, Baricich A, Zeppegno P, Avanzi GC, et al. Respiratory and psychophysical sequelae among patients with COVID-19 four months after hospital discharge. JAMA Netw Open 2021;4:e2036142. |
| 8. | Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, et al. Features of 20133 UK patients in hospital with covid-19 using the ISARIC WHO clinical characterisation protocol: Prospective observational cohort study. BMJ 2020;369:m1985. |
| 9. | Dennis A, Wamil M, Alberts J, Oben J, Cuthbertson DJ, Wootton D, et al. Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: A prospective, community-based study. BMJ Open 2021;11:e048391. |
| 10. | Garrigues E, Janvier P, Kherabi Y, Le Bot A, Hamon A, Gouze H, et al. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J Infect 2020;81:e4-6. |
| 11. | Alkodaymi MS, Omrani OA, Fawzy NA, Shaar BA, Almamlouk R, Riaz M, et al. Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: A systematic review and meta-analysis. Clin Microbiol Infect 2022;28:657-66. |
| 12. | Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA 2020;323:1239-42. |
| 13. | Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271-80.e8. |
| 14. | Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004;203:631-7. |
| 15. | Hyrich KL, Machado PM. Rheumatic disease and COVID-19: Epidemiology and outcomes. Nat Rev Rheumatol 2021;17:71-2. |
| 16. | Lu C, Li S, Liu Y. Role of immunosuppressive therapy in rheumatic diseases concurrent with COVID-19. Ann Rheum Dis 2020;79:737-9. |
| 17. | Recovery Collaborative Group, Horby P, Mafham M, Linsell L, Bell JL, Staplin N, et al. Effect of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med 2020;383:2030-40. |
| 18. | Recovery Collaborative Group. Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet Respir Med 2021;9:1419-26. |
| 19. | Recovery Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021;384:693-704. |
| 20. | Recovery Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet 2021;397:1637-45. |
| 21. | Bartoszko JJ, Siemieniuk RAC, Kum E, Qasim A, Zeraatkar D, Ge L, et al. Prophylaxis against covid-19: Living systematic review and network meta-analysis. BMJ 2021;373:n949. |
| 22. | Ursini F, Ciaffi J, Mancarella L, Lisi L, Brusi V, Cavallari C, et al. Fibromyalgia: A new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey. RMD Open 2021;7:e001735. |
| 23. | Gracia-Ramos AE, Martin-Nares E, Hernández-Molina G. New onset of autoimmune diseases following COVID-19 diagnosis. Cells 2021;10:3592. |
| 24. | Batıbay S, Koçak Ulucaköy R, Günendi Z, Göğüş F. The prevalence and clinical spectrum of post-Covid syndrome in patients with rheumatic diseases: A single-center experience. Reumatismo 2022;74:22-8. [doi: 10.4081/reumatismo.2022.1481]. |
| 25. | Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, et al. More than 50 long-term effects of COVID-19: A systematic review and meta-analysis. Sci Rep 2021;11:16144. |
| 26. | Greenhalgh T, Knight M, A'Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ 2020;370:m3026. |
| 27. | Nath A. Long-haul COVID. Neurology 2020;95:559-60. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]
|
