COVID-19 among Rheumatoid Arthritis Patients on ‎Immunosuppressive Therapy During the First Wave of the COVID-‎‎19 Pandemic: a Prospective Comparative Study ‎

INTRODUCTION

Coronavirus disease 2019 (COVID-19) has quickly become a pandemic virus that has resulted in severe morbidity and mortality around the world. Since the outbreak of COVID-19 in late 2019, global healthcare systems have faced numerous problems, ranging from many patients to a shortage of approved therapy alternatives. A lot of work has been done around the world to find effective ways to treat the virus [1].

According to the World Health Organization, there is insufficient evidence to recommend any specific COVID-19 treatment for patients who have been diagnosed with COVID-19 [2]. RA is a T-cell and B-cell-mediated autoimmune disease that primarily affects the joints but can also cause systemic symptoms [3]. The profile of RA includes increased levels of proinflammatory cytokines, tumor necrosis factor (TNF) and interleukin (IL6) [4], which is similar to the profile of COVID-19 [5], as disease severity of COVID-19 was correlated with hypercytokinaemia, characterized by increased serum IL-2, IL-7, IL-10, granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein 1, and granulocyte chemoattractant protein 1 [6].

People with rheumatic and musculoskeletal diseases have been impacted during this pandemic through their greater risk of infection due to immune dysregulation, comorbidities, and immune modulating treatments [7]. At the same time, many of these immune modulating treatments (e.g., hydroxychloroquine [HCQ], glucocorticoids [GCs], interleukin1 [IL1], IL6 inhibitors, JAK inhibitors) are being tested to prevent or treat COVID-19 [8], which have caused some confusion and concerns about the actual risks posed to individuals with rheumatic and musculoskeletal diseases [9]. Also, the available data on COVID19 infection rates and outcomes among patients receiving disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis are quite reassuring [10]. To date, data on the epidemiology of COVID-19 in rheumatoid arthritis patients is still scarce.

Therefore, this study was conducted to study COVID-19 severity and outcome among rheumatoid arthritis patients, including hospitalization, ICU admission, and mortality compared to others.

PATIENTS AND METHODS

Study design and setting:

A prospective comparative study was undertaken on 146 patients at Zagazig University Hospitals from July to December 2020 .Protocols from the Egyptian Ministry of Health and Population were used to treat the people who took part in the study.

Participants:

They were divided into 3 groups: Group I: Included 52 patients suffering from RA,Group II included 44 patients suffering from RA with COVID-19, Group III included 50 COVID-19 patients.

The RA with COVID-19 cohort included all patients who were 18 years of age or older, had a pre-existing diagnosis of RA, and were diagnosed with COVID-19 anytime from January 20, 2020 to December 2020. The diagnosis of RA was based on the 2010 ACR/EULAR criteria for RA [11], and the diagnosis of COVID-19 was based on clinical findings and SARS-CoV-2 polymerase chain reaction (PCR) positivity. The comparison group was made up of any adult without a known history of RA who was diagnosed with COVID-19 between January 20, 2020 and December 20, 2020.

Instruments and tools for data collection:

-       Demographic characteristics (age, sex, level of education, marital status, special habits, and Occupation).

-       The practice of preventive measurement (Hygienic hands wash, safe space more than two meter, surfaces disinfectants, and wearing masks).

-       Data on RA-related parameters:

1. The disease's duration,
2. The clinical evaluation:

• The Modified Health Assessment Questionnaire (MHAQ) is a self-reported outcome questionnaire that helps doctors figure out how well RA patients can do their jobs. It included questions about the perceived patient’s satisfaction regarding the same daily activities as well as the change in the degree of difficulty [12].
• The disease activity of RA patients was calculated using the Modified Disease Activity Score (DAS-28) [13], equation with the number of swollen joints (NSJ), number of tender joints (NTJ), ESR, and patient response on visual analogue using the Global Assessment (PGA) of disease activity. DAS classified A patients as mild (2.4), moderate (2.5-3.7), or severe (> 3.7) [14].

1. The RA treatment protocol's: Medication for RA patients from medical records included conventional synthetic DMARDs as methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide.

-  COVID-19 symptoms and outcomes

1. The acute COVID-19 symptoms.
2. COVID-19 outcomes included mortality, hospitalization, intensive care unit-ICU admission, mechanical ventilation, severe COVID-19 (a composite of mechanical ventilation and mortality), and acute respiratory distress syndrome-ARDS. All examined outcomes were assessed within 30 days after the COVID-19 diagnosis.
3. The COVID 19 treatment protocol's; a uniform prescription form was produced and issued with the documented treatment protocol. The prescription called for hydroxychloroquine to be taken for five days, starting with 400 mg twice a day on day one and then 200 mg twice a day for the next four days. Patients with renal or hepatic impairment should not modify their dose. Zinc sulphate, 60 mg orally once daily for 5 days, paracetamol, and an antihistamine were also included in the prescription. The antibiotic azithromycin was not included in the prescription. Follow up within 3-7 days after starting therapy.

Data analysis:

The outcome variables included reported treatment protocol outcomes such as the percentages of patients who were hospitalized, admitted to the ICU, or died. IBM SPSS Statistics version 21 was used to analyze all the data. Considerations on morality Following a description of the study, the treating physician got informed permission from the participants. Those who refused to participate in the trial were removed from the study and were given standard supportive care instead. All information gathered will be kept private and used solely for the purpose of the study. Patients who were unstable at the time of presentation or who showed clinical progression/deterioration on days 3-7 were referred to the hospital, and the study team followed up on their progress.

RESULTS

This study included 146 randomly selected   patients attending Zagazig university hospitals. The socio-demographic characteristics of the participants are shown in [table 1]. The three studied groups were matched and showed no statistically significant difference (p > 0.05) as regards age, sex, level of education, and marital status. But there was a statistically significant difference between the groups in terms of occupation and smoking hashish.

There was a statistically significant difference (p < 0.05) as regards the practice of preventive measurements (including safe spacing greater than 2 meters, applying surface disinfectants, and always wearing masks) among the studied groups except hygienic hands wash to be significantly higher among the RA group and Group II (RA and COVID19) in comparison   to COVID - 19 infected cases [table 2].

There was an analytical difference, as regards the acute symptoms of COVID-19 among the studied groups, between the studied RA group (Group 1) in comparison with the other groups; COVID-19 cases (COVID-19 only and Rheumatoid with COVID-19). There was no marked difference in symptoms between group II and group III but both had significantly more symptoms than RA group, in other terms all symptoms increase with COVID-19 infection (group 2 and 3) except fatigue (non-significant). COVID-19 infection is accompanied by significant worsening of symptoms in RA with COVID-19 group compared to the COVID-19 group. RA with COVID-19 (group II) patients suffered from 38 (86.4%) muscle pain, 40(90.9%) fatigue, and 36 (81.8%) sore throat. COVID-19 group had presented with more fever 46 (92.0%), headaches 34 (68.0%) and skin rash 36(72%) than combined disease [Table 3], after adjusting for gender and occupation with binary logistic regression models, there were statistically significant differences between groups 2 and 3, RA with COVID-19 group did tend toward higher hospital admission rates (OR 0.81, 95% CI 0.35-0.88, p = 0.03) [table 4].  As regards the clinical assessment of RA, The mean of MHAQ was 5.5 in RA group versus 8 in RA-COVID-19 group ,with ‎ statistically significant difference between group I and II as regard DAS28, the time from diagnosis to recovery was significantly shorter than in COVID-19 cases [table 5]. As regards the medications and their outcomes [table 6].

Table (1): The Demographic Characteristics of the Studied Groups.

*p

Table (2): The Practice of preventive measurements among the studied groups.

*p

Table (3): The acute symptoms of COVID-19 among the studied groups.

*p

Table (4): COVID-19 complication and outcome among the studied groups.

*p

Table (5): The clinical assessment of Rheumatoid arthritis among the studied groups.

*p

Table (6): The Frequency Distribution of Medications among the studied groups.

* p < 0.05 there was a statistically significant difference

DISCUSSION