|Year : 2021 | Volume
| Issue : 1 | Page : 17-22
The pattern and factors associated with COVID-19 infection among rheumatology patients
Huda Alfaris1, Eiad Alfaris2, Fahidah AlEnzi3, Farhana Irfan2, Lina El Kibbi4, Hanan Alrayes1
1 Department of Medicine, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
2 Department of Family and Community Medicine, King Saud University Chair of Medical Education Research and Development, College of Medicine, King Saud University, Riyadh, Saudi Arabia
3 Department of Clinical Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
4 Department of Medicine, Specialized Medical Center, Riyadh, Saudi Arabia
|Date of Submission||06-Jul-2021|
|Date of Decision||18-Aug-2021|
|Date of Acceptance||02-Sep-2021|
|Date of Web Publication||13-Nov-2021|
Dr. Huda Alfaris
Department of Medicine, Prince Sultan Military Medical City, Riyadh
Source of Support: None, Conflict of Interest: None
Objectives: The global coronavirus pandemic has led to a considerable concern among rheumatologists regarding the possible higher risk of infection and complications among their patients. The severity and outcome of coronavirus disease 2019 (COVID-19) infection among patients with rheumatic disease (RD) need to be studied to help guide physicians choose the best approach for different categories of patients. Therefore, we aimed to estimate the rate of COVID-19 infection among RD patients and to evaluate the risk factors and outcomes. Methodology: This study was a cross-sectional questionnaire-based study. A convenience and nonprobability sample of RD patients filled out the study questionnaire from October to November 2020. They were invited digitally through SurveyMonkey and were recruited from social support group sites of the Saudi Society of Rheumatology and the Charitable Association for Rheumatic Diseases. The Chi-square test, Mann–Whitney test, and Fisher's exact test were used as appropriate. Continuous data are expressed as the mean and standard deviation. A P < 0.05 was considered as statistically significant. Results: The study participants were composed of 530 RD patients. The ages of the participants ranged from 14 to 80 years, and women outnumbered men with a ratio 4.4:1 (329 female and 96 male patients). The rate of COVID-19 infection among the study population was 13.7% (n = 71). Previous comorbidities (liver disease and heart failure) were associated with higher risk of COVID-19 infection (P < 0.01 and 0.012) and worse outcome (P < 0.005). Conclusion: This study indicates a relatively high rate of COVID-19 infection among RD patients. Having comorbidities posed a significantly greater risk for contracting COVID-19 infection and developing worse outcomes. Therefore, close monitoring of patients with comorbidities such as liver and cardiovascular diseases is warranted.
Keywords: COVID, factors, pattern, rheumatology
|How to cite this article:|
Alfaris H, Alfaris E, AlEnzi F, Irfan F, El Kibbi L, Alrayes H. The pattern and factors associated with COVID-19 infection among rheumatology patients. Ann Rheumatol Autoimmun 2021;1:17-22
|How to cite this URL:|
Alfaris H, Alfaris E, AlEnzi F, Irfan F, El Kibbi L, Alrayes H. The pattern and factors associated with COVID-19 infection among rheumatology patients. Ann Rheumatol Autoimmun [serial online] 2021 [cited 2021 Nov 29];1:17-22. Available from: http://www.ara.ssr.com/text.asp?2021/1/1/17/330430
| Background|| |
A novel coronavirus was identified by the end of 2019 in Wuhan, China, which resulted in a pandemic and a worldwide increase in morbidity and mortality. By the end of September 2020, the reported number of people infected with coronavirus disease 2019 (COVID-19) was more than 20 million globally. In Saudi Arabia, as of August 5, 2021, around 530,000 confirmed cases of COVID-19, including 8284 deaths, have been reported. The pandemic has posed many challenges, and the medical community has had to fight against this rapidly spreading disease.
The clinical spectrum of COVID-19 infection ranges from asymptomatic and mild to moderate flu-like symptoms, a severe acute respiratory distress syndrome-like picture, and potential death. The clinical presentation of COVID-19 might mimic some rheumatic diseases (RDs). In addition, COVID-19 may trigger some RDs. For example, cases of Kawasaki disease, and reactive arthritis, have been reported following COVID-19 infection. COVID-19 may present with some possible manifestations of an RD or might often trigger some RDs. Thus, appropriate clinical judgment should be exercised to differentiate between RD activity and infection with COVID-19.
There is an ongoing dialog about whether having a rheumatological disease increases the risk of contracting COVID-19 among vulnerable patients. In particular, it is not yet clear whether those on immunosuppressive drugs are more vulnerable to infections. However, studies have shown that patients with RD are more likely to have multiple comorbidities and are usually on immunosuppressive therapies, so they are more vulnerable to infections. The mortality rate is around 12 times higher in patients with comorbidities compared to individuals with no other medical conditions.
While it is well known that immunosuppressive therapies are associated with a higher risk for infections, the data regarding the risk of the development of COVID-19 infection among patients on antirheumatic drugs are inconsistent., Therefore, rheumatologists are advised to be vigilant about the potential complications, and decisions regarding the alteration of immunosuppressant medications should be made on an individual basis.
RDs have diverse presentations, and patients can be at a higher risk for contracting COVID-19 if they have comorbidities. Thus, information about factors such as disease activity, comorbidities, and use of drugs is needed to better understand the impetus of increased risk and death phenomenon. Therefore, it is necessary to identify the features among RD patients who are at risk of contracting COVID-19 for their optimal management.
Unfortunately, insufficient data exist on COVID-19 infection among patients with RD in Arab regions, particularly Saudi Arabia. Therefore, we aimed to estimate the rate, severity, and factors associated with COVID-19 infection among patients diagnosed with different RDs. The objectives of this study were to estimate the rate of COVID-19 infection among RD patients during the pandemic and to determine the factors associated with COVID-19 infection and its severity.
| Methods|| |
The study design was an observational cross-sectional study, and the target population was all RD patients of both sexes living in Saudi Arabia who were above 14 years of age, regardless of nationality and other demographic factors. For sampling, Raosoft software was used to estimate the required sample size based on the estimated parameters for the study population. For a total of >10,000 patients with a 95% confidence level and 5% margin of error, the minimum sample size was estimated to be 383 patients. A convenience and nonprobability sample of RD patients was invited to fill out the electronic questionnaire through SurveyMonkey. After obtaining a sample of 530 patients, the enrolment of patients was ended.
A 31-item questionnaire was developed after a literature search and going through questionnaires from similar studies. All the authors, who were content experts, participated in this process and agreed on the items used. A pilot study was conducted with 10 people, and unclear items were modified. The questionnaire consisted of two parts:
- Questions about demographic data, primary diagnosis, and adherence with medications
- Questions seeking information on whether the patient had COVID-19 infection; the date, symptoms, and risks of infection; hospital/ICU admission; and outcome.
Data were collected from October 1 to November 14, 2020. Because of lockdown conditions, a digital questionnaire was used. It was uploaded to SurveyMonkey through a link sent to the target population. Participation was on a voluntary basis. The patients were invited to participate in the study through social support group sites: The Saudi Society of Rheumatology and the Charitable Association for Rheumatic Diseases. Relatives and attendants were allowed to fill out the survey if the patients were unable to do so or for those who had died from COVID-19 infection.
Data analysis plan
Data were coded, tabulated, and analyzed using SPSS version 25 statistical software package (IBM SPSS). Descriptive statistics such as frequencies, percentages, means, and standard deviations (SDs) were calculated for sociodemographic data. The study population was divided into patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and others as a combined group; A subgroup analysis was performed to evaluate for infection, management requirements and related complications between disease subgroups namely SLE versus the rest or RA versus the rest of the cohort. The Chi-square (χ2) test was applied to test the relationship between variables. Quantitative data were expressed as mean ± SD, and the Mann–Whitney test was applied for nonparametric variables. A P < 0.05 was considered as statistically significant.
| Results|| |
Out of the 530 patients who answered the questionnaire, 13 patients were excluded (1 below 14 years old, 6 with a primary diagnosis of fibromyalgia, and 6 were outside the country), leaving 517 patients for final data analysis. The majority of the participants were Saudi (81.2%), female (85.9%), and 18–65 years of age (95.4%). More than half of them (56.3%) lived in the central region of Saudi Arabia. Around half (51%) of the participants had a bachelor's degree or higher, and 51.1% were unemployed.
The most frequent diagnoses were SLE (37.1%) and RA (35%), followed by Behcet's disease (7%), polymyalgia rheumatica (3.1%), and ankylosing spondylitis (3.1%). The rate of COVID-19 infection among rheumatology patients during the pandemic was 13.7% (n = 71). Around 35% of patients who contracted COVID-19 infection had RA and SLE as the primary RD (32%). Only a small proportion of patients (1.4%) were current smokers, and 60.6% had comorbidities. Among the patients who developed COVID-19 infection, 8.6% were admitted to the intensive care unit (ICU), 26.8% required oxygen supply, and 12.7% needed mechanical ventilation. As for COVID-19 complications, 36.6% of the patients had some complications at home, and two (2.8%) died.
No significant association was detected between the three disease categories namely SLE, RD, and others on the one hand and different management options and prognosis [Table 1].
|Table 1: Relationship between categories and both the need for respiratory support and whether admitted to hospital among patients infected with coronavirus disease-2019 (n=71)|
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The most frequent symptom among COVID-19 patients was joint pain (70.4%), followed by muscle pain (64.8%) and fever (60.6%). The most frequently used antirheumatic drug was hydroxychloroquine (11 patients), followed by hydroxychloroquine combined with other immunosuppressive drugs (5 patients) [Figure 1]. A statistically significant association was found between the presence of comorbidities such as cardiac or liver diseases and the likelihood of having COVID-19 infection [Table 2]. However, no association was found between COVID-19 diagnosis and age (P = 0.81), gender (P = 0.315), nationality (P = 0.381), history of influenza vaccination (P = 0.858), smoking status (P = 0.49), and multiple comorbidities such as chronic kidney disease (P = 0.863), hypertension (P = 0.585), diabetes mellitus (P = 0.47), obesity (P = 0.561), and malignancy (P = 0.69) [Figure 2].
|Figure 1: The most frequently used antirheumatic drugs among COVID-19–infected patients (No. 71)|
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|Figure 2: Percentage of complete cure versus complication or death in relation to comorbidities|
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|Table 2: Comparison between rheumatic disease patients with and without coronavirus disease-2019 infection regarding the disease type, smoking status, and presence of comorbidities (n=517)|
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No significant association was found between the outcome and the drugs used, including hydroxychloroquine monotherapy or in combination with other drugs (steroids, mycophenolate, or methotrexate), as well as other drugs that do not contain hydroxychloroquine, such as methotrexate, antitumor-necrosis-factor, azathioprine, and rituximab (P = 0.6224). A significant association was detected between having comorbidities and the outcome of COVID-19 infection (P = 0.049). However, no association was detected between age and the outcome of COVID-19 infection (P = 0.668) [Table 3]. Shows the outcomes observed after COVID-19 infection among RD patients.
|Table 3: Relationship between drugs used and presence of morbidities on one hand and the outcome of coronavirus disease-2019 infection among infected patients (n=71)|
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| Discussion|| |
The rate of COVID-19 infection among RD patients is higher than the total population. The total number of positive COVID-19 cases detected constitutes 0.7% of the Saudi population as compared to 13.7% in this study. This finding in line with previous studies finding that show patients affected by RD are at an increased risk of infection compared to the general population.
To the best of our knowledge, this is one of the first few reports of a cross-sectional study of patients with RD and COVID-19 in Saudi Arabia. Of all patients, more women were affected by COVID-19 which is in line with other studies, and it was expected since most RD show a considerable preponderance of females. However, sex was not found to be a statistically significant factor for contracting the COVID-19 disease. In addition, we found a low prevalence of smoking in our subjects, which is in line with previous data from the region. A possible explanation could be relatively low prevalence of female smokers in the Saudi culture. However, there was no significant association between smokers and nonsmokers which is not in line with the literature that shows active smoking to increase the risk of having severe COVID-19.
In the study cohort, the most prevalent rheumatic diseases was SLE (37.1%) followed by RA (35%), which is contrast to a recent study published among RD patients with COVID-19 in Saudi Arabia that showed RD (53.2%), followed by SLE (21.3%). As this observation is based on a very small group of patients, it should be confirmed in larger studies. This study reports 35% of RD; the prevalence of RA in the Kingdom of Saudi Arabia is estimated to be 2.2 per thousand people. Currently, epidemiological results found in the literature regarding RA in SA are suboptimal. In fact, the exact prevalence of RA in the Saudi population remains uncertain.
Saudi Arabia's digital response to the COVID-19 pandemic is noteworthy. MOH established call centers to answer inquiries related to COVID-19, teleconsultation apps, WhatsApp was the preferred messaging app, some hospitals and medical centers-initiated WhatsApp numbers to help patients register their medication refill requests, arrange for remote routine follow-ups, and inquire regarding their laboratory results (e-prescription) services. These services are on par with those used worldwide.
In the current study, the presence of comorbidities was associated with poor outcome after COVID-19 infection. The higher rate of COVID-19 infection among RD patients compared to the general population is not in line with a different trial that found similar rates. In a meta-analysis that included data on immunocompromised RD patients from 15 countries, the rate of COVID-19 infection (1.1%) and another study in 15 Arab countries (2.8%), which is much lower than in the current study (13.7%). There are considerable heterogeneities. A few plausible explanations for such differences could be potentially explained by a relatively small sample size of the study, use of drugs, before developing COVID-19, study location, the sensitivity of nasopharyngeal swab. Hence, these issues might affect the result of the prevalence data. The outlook of COVID-19 research is rapidly changing, and therefore, it is difficult to draw firm conclusions as the evidence of epidemiological implication of this outbreak on these vulnerable populations is limited. Overall, future studies on the reasons for higher rate of infection among Saudi population are needed. This finding could be attributed to the differences between the regions and countries, distribution of the disease, and disease-specific factors such as disease activity, level of control with medications, and frequency of comorbidities.
In this cohort of RD patients, no association was found between the diagnosis of COVID-19 and other sociodemographic factors such as of age, sex, nationality, region of residence, educational status, and occupation. This is in line with previous studies findings. Moreover, the presence of comorbidities was associated with higher risk of COVID-19 infection and worse outcome. Comorbidities in RDs have obtained an extreme significance as they are associated with increased risks of complications in the present era of coronavirus-19 pandemic. The findings of the study show a significant association with the cardiovascular disease, heart failure, which is in line with the literature as the one of the most common comorbidities. This is comparable with the findings of the COVID-19 Global Rheumatology Alliance regarding the presence of additional underlying health conditions being associated with hospitalization. Patients with liver disease and heart failure also showed a positive association in the current study. Thus, it is recommended for treating physicians to be more vigilant with RD patients who have comorbidities. This relationship is bidirectionally detrimental.
Our cohort showed a significantly low rate of mortality (0.4%) compared to a study locally and worldwide reporting a mortality rate ranging from 2.1% to 19%.,,
The present study showed no specific association between Disease-modifying antirheumatic drug (DMARD) and the outcome, which is similar to the results of a study by Santos et al. Among the COVID-19 symptoms, joint pain (70.4%), muscle pain (64.8%), and fever (60.6%) were the most commonly reported symptoms by our patients which is inconsistent with the report of previous study that showed fever, myalgia, and cough (78.7%, 78.7%, and 74.5%, respectively).
This knowledge is valuable for the physicians treating patients with RD during this pandemic, as it can serve as guidance for them to be more vigilant.
The current study has some limitations. The convenience nonprobability sampling increased the likelihood of bias. Furthermore, the nature of the data collection in which patients who volunteered and were willing to fill out the questionnaire may have reduced the proportion of patients who were not well versed with the internet and social media use, those who were less educated, and older patients. For example, only one patient was above 65 years of age. The use of age and sex matched control group to show the difference between non-RD controls and RD patients in relation to COVID-19 affection is beyond the capacity of the paper as there is no control. Nevertheless, we believe that the findings of this study could guide rheumatologists in this period of dilemma in risk factors and patients' management.
| Conclusion and Recommendations|| |
This study indicates a high rate of COVID-19 infection among RD patients. Having comorbidities posed a significantly greater risk for contracting COVID-19 infection and developing worse outcomes. Therefore, close monitoring of patients with comorbidities such as liver and cardiovascular diseases is warranted. It is recommended that treating physicians be more vigilant with RD patients who have comorbidities, particularly liver disease, and heart failure.
We thank the Saudi Society for Rheumatology and the Charitable Association for Rheumatic Diseases for their permission and help in the data collection.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jones VG, Mills M, Suarez D, Hogan CA, Yeh D, Segal JB, et al
. COVID-19 and Kawasaki disease: Novel virus and novel case. Hosp Pediatr 2020;10:537-40.
Shaigany S, Gnirke M, Guttmann A, Chong H, Meehan S, Raabe V, et al
. An adult with Kawasaki-like multisystem inflammatory syndrome associated with COVID-19. Lancet 2020;396:e8-10.
Ono K, Kishimoto M, Shimasaki T, Uchida H, Kurai D, Deshpande GA, et al
. Reactive arthritis after COVID-19 infection. RMD Open 2020;6:e001350.
Liew IY, Mak TM, Cui L, Vasoo S, Lim XR. A case of reactive arthritis secondary to coronavirus disease 2019 infection. J Clin Rheumatol 2020;26:233.
Mikuls TR. Co-morbidity in rheumatoid arthritis. Best Pract Res Clin Rheumatol 2003;17:729-52.
Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S, et al
. Coronavirus disease 2019 case surveillance – United States, January 22-May 30, 2020. MMWR Morb Mortal Wkly Rep 2020;69:759-65.
Atzeni F, Masala IF, di Franco M, Sarzi-Puttini P. Infections in rheumatoid arthritis. Curr Opin Rheumatol 2017;29:323-30.
Monti S, Balduzzi S, Delvino P, Bellis E, Quadrelli VS, Montecucco C. Clinical course of COVID-19 in a series of patients with chronic arthritis treated with immunosuppressive targeted therapies. Ann Rheum Dis 2020;79:667-8.
Damiani G, Pacifico A, Bragazzi NL, Malagoli P. Biologics increase the risk of SARS-CoV-2 infection and hospitalization, but not ICU admission and death: Real-life data from a large cohort during red-zone declaration. Dermatol Ther 2020;33:e13475.
Mikuls TR, Johnson SR, Fraenkel L, Arasaratnam RJ, Baden LR, Bermas BL, et al
. American college of rheumatology guidance for the management of rheumatic disease in adult patients during the COVID-19 pandemic: Version 2. Arthritis Rheumatol 2020;72:e1-12.
Alahmari AA, Khan AA, Elganainy A, Almohammadi EL, Hakawi AM, Assiri AM, et al
. Epidemiological and clinical features of COVID-19 patients in Saudi Arabia. J Infect Public Health 2021;14:437-43.
Hasseli R, Mueller-Ladner U, Schmeiser T, Hoyer BF, Krause A, Lorenz HM, et al
. National registry for patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 in Germany (ReCoVery): A valuable mean to gain rapid and reliable knowledge of the clinical course of SARS-CoV-2 infections in patients with IRD. RMD Open 2020;6:e001332.
Fairweather D, Frisancho-Kiss S, Rose NR. Sex differences in autoimmune disease from a pathological perspective. Am J Pathol 2008;173:600-9.
Alzahrani ZA, Alghamdi KA, Almaqati AS. Clinical characteristics and outcome of COVID-19 in patients with rheumatic diseases. Rheumatol Int 2021;41:1097-103.
Zhao Q, Meng M, Kumar R, Wu Y, Huang J, Lian N, et al
. The impact of COPD and smoking history on the severity of COVID-19: A systemic review and meta-analysis. J Med Virol 2020;92:1915-21.
Almoallim HM, Alharbi LA. Rheumatoid arthritis in Saudi Arabia. Saudi Med J 2014;35:1442-54.
Hassounah M, Raheel H, Alhefzi M. Digital response during the COVID-19 pandemic in Saudi Arabia. J Med Internet Res 2020;22:e19338.
Favalli EG, Monti S, Ingegnoli F, Balduzzi S, Caporali R, Montecucco C. Incidence of COVID-19 in patients with rheumatic diseases treated with targeted immunosuppressive drugs: What can we learn from observational data? Arthritis Rheumatol 2020;72:1600-6.
Akiyama S, Hamdeh S, Micic D, Sakuraba A. Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis. Ann Rheum Dis. 2020 Oct 13:annrheumdis-2020-218946. doi: 10.1136/annrheumdis-2020-218946. Epub ahead of print. PMID: 33051220; PMCID: PMC7554412.
Ziadé N, El Kibbi L, Hmamouchi I, Abdulateef N, Halabi H, Hamdi W, et al
. Impact of the COVID-19 pandemic on patients with chronic rheumatic diseases: A study in 15 Arab countries. Int J Rheum Dis 2020;23:1550-7.
Strangfeld A, Schäfer M, Gianfrancesco MA, Lawson-Tovey S, Liew JW, Ljung L, et al
. COVID-19 Global Rheumatology Alliance. Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2021 Jul;80(7):930-942. doi: 10.1136/annrheumdis-2020-219498. Epub 2021 Jan 27. PMID: 33504483; PMCID: PMC7843211.
Santos CS, Morales CM, Álvarez ED, Castro CÁ, Robles AL, Sandoval TP. Determinants of COVID-19 disease severity in patients with underlying rheumatic disease. Clin Rheumatol 2020;39:2789-96.
Hyrich KL, Machado PM. Rheumatic disease and COVID-19: Epidemiology and outcomes. Nat Rev Rheumatol 2021;17:71-2.
Zaky S, Alboraie M, El Badry M, Metwally MA, Abdelaziz A, Fouad Y, et al
. Management of liver disease patients in different clinical situations during COVID-19 pandemic. Egypt Liver J 2021;11:21.
D'Silva KM, Serling-Boyd N, Wallwork R, Hsu T, Fu X, Gravallese EM, et al
. Clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and rheumatic disease: A comparative cohort study from a US 'hot spot'. Ann Rheum Dis 2020;79:1156-62.
Sanchez-Piedra C, Diaz-Torne C, Manero J, Pego-Reigosa JM, Rúa-Figueroa Í, Gonzalez-Gay MA, et al
. Clinical features and outcomes of COVID-19 in patients with rheumatic diseases treated with biological and synthetic targeted therapies. Ann Rheum Dis 2020;79:988-90.
Santos CS, Férnandez XC, Moriano Morales C, Álvarez ED, Álvarez Castro C, López Robles A, et al
. Biological agents for rheumatic diseases in the outbreak of COVID-19: Friend or foe? RMD Open 2021;7:e001439.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]