Successful management of a case of SARS‐CoV‐2 infection in an advanced Rheumatoid Arthritis patient by dose reduction of immunosuppressive medication

Ahmadreza Bazmjoo Jahrom University of Medical Sciences, Jahrom, Iran Mohammad Aref Bagherzadeh Jahrom University of Medical Sciences, Jahrom, Iran Farida Farahmandpoor Fasa University of Medical Sciences, Fasa, Iran Rahim Raoo Jahrom University of Medical Sciences, Jahrom, Iran Amir Abdoli (  a.abdoli25@gmail.com ) Jahrom University of Medical Sciences, Jahrom, Iran https://orcid.org/0000-0003-4326-4586


Introduction
In late 2019, pneumonia due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, which has immediately spread around the world [1]. The major clinical manifestations of COVID-19 include a range from asymptomatic presentation to acute respiratory distress syndrome (ARDS) [2,3]. The disease has more sequels in >60 years older patients and those who have comorbidities, such as pulmonary diseases, chronic kidney diseases, diabetes, and also impaired immune systems [4][5][6]. Rheumatoid Arthritis (RA) is a chronic autoimmune in ammatory disorder that affects joints more than other parts and sometimes associated with the number of comorbidities [7]. The treatment strategy of RA is based on Disease-modifying anti-rheumatic drugs (DMARDs) and corticosteroids, hence RA patients have a higher risk of infection, including the COVID-19 [7]. However, limited data are available about the severe case of COVID-19 in Rheumatoid Arthritis (RA) patients [8][9][10][11][12].
Here we present a complicated case of SARS-CoV-2 infection in a 49-year-old female.

Case Presentation
A 49 years-old woman admitted to the hospital (Valiye Asr hospital, Iran, Fars, Fasa) at 11, March 2020 with a dry cough, fever, myalgia, respiratory distress, dizziness and nausea. Though O2 Saturation (SPO2%) was low (%) on the admission, O2 nebulizer administered (O2 5 lit/min), which resulted in the correction of O2 Saturation (87%) very soon (Table 1 and Supplementary Figure 1, A, B, and C and   Supplementary table 1). Four days before admission, she had only dry cough without other symptoms.
She declared no sign of reduced smell and taste senses. Before admission, she had a history of contact with her two daughters, her husband, and 1-year-old grandchildren, that all of them were positive for COVID-19 by real-time PCR test. She was the only member of her family with severe respiratory problems that needed to be hospitalized (and also the only person with RA in her family), whiles the rest of the family showed mild symptoms and quarantined at home. The Chest x-rays on the rst day of hospitalization showed pneumonia signs alongside with bilateral ground-glass pattern, vascular dilation, and traction bronchiectasis in the middle and secondary lobes (Figure 1, A, B, and C). Positive Real-time PCR tests con rmed the SARS-CoV-2 infection. Laboratory ndings on admission was a very low WBC count and reduced number of platelets, elevated ESR and PT (Table 1 and Supplementary table 2  Therapy with Hydroxychloroquine was started on the 1st day and continued for 10 days. Oseltamivir was added on the 2nd day and continued for 6 days. The patient's nausea was controlled by Ranitidine, Ondansetron, and Pantoprazole. Kaletra (Lopinavir/Ritonavir 200-50 mg/day and night 2 tab each) was added to the antiviral regimen on the 4th day, continued as the main antiviral medication for 7 days until symptoms relieved. A cluster of Antibiotics was prescribed for the rst week because of low WBC count and suppressed immunity to prevent secondary infection. In the following, she was treated with one period of Levo oxacin medication in the last week. Theophylline G and O2 Nebulizer treatment helped to support the airway and reduce the respiratory symptoms (Table 1
The results of this case have shown that a gradual reduction of immunosuppressive drugs led to decline the disease severity. Immunosuppressive medication in RA patients (e.g., csDMARDs and corticosteroids) in the course of SARS-CoV-2 infection may be as a double-edged sword [13]. Managing the RA disease with the lowest possible dose of csDMARDs besides antiviral therapy against SARS-CoV-2 could be an effective strategy for treatment of COVID-19 in RA patients.
Previous studies demonstrated the increased risk of infection as an adverse effect of corticosteroids [14,15]. Our report also con rms this fact. Although some previous studies clari ed that receiving Methotrexate is not associated with increased risk of infection in RA patient, previous ndings are inconsistent with the results of our study [16,17]. On the other hand, the most important cause of lung tissue damage and respiratory distress is due to the cytokine release storm (CRS) caused by the immune system in response to SARS-CoV-2. Patients with RA who are being treated with immunosuppressive drugs such as corticosteroids and methotrexate have weakened immune systems, and this weakness puts forward this theory that they are safe from CRS and its destructive effects [18]. This is not con rmed in our case.
In this case report, all the family members were infected with the virus at the same time, only this patient with RA presented with severe respiratory symptoms and needed to be admitted to hospital. These conditions may indicate that a defect in the immune system caused by rheumatoid arthritis or as a result of medication has led the patient to acute respiratory illness caused by contamination with COVID 19 [8].