key: cord-278306-wdj5v3rh
authors: Alharthy, Abdulrahman; Faqihi, Fahad; Nasim, Nasir; Noor, Alfateh; Akhtar, Saima; Balshi, Ahmed; Balhamar, Abdullah; Alqahtani, Saleh A.; Memish, Ziad A.; Karakitsos, Dimitrios
title: COVID-19 in a patient with a flare of systemic lupus erythematosus: a rare case-report
date: 2020-10-15
journal: Respir Med Case Rep
DOI: 10.1016/j.rmcr.2020.101252
sha: 
doc_id: 278306
cord_uid: wdj5v3rh

This is a rare case-report of a young female with systemic lupus erythematosus and end-stage kidney disease (on maintenance hemodialysis) who was admitted to our intensive care unit due to life-threatening COVID-19. The patient was diagnosed with a flare of lupus; while being on maintenance hydroxychloroquine therapy. However, after the administration of steroids she made an uneventful recovery and was discharged home. In this report, the diagnostic dilemmas and the therapeutic challenges due to the overlapping clinical, imaging, and laboratory findings between lupus and COVID-19 pneumonitis are outlined. In conclusion, patients with lupus may be affected by COVID-19 despite the administration of hydroxychloroquine. The administration of steroids may have a beneficial effect on mitigating both the flare of SLE and the COVID-19 associated hyperinflammation.

The novel coronavirus SARS-CoV-2 disease (COVID-19) emerged in Wuhan, the capital of Hubei province, in China, and progressively spread worldwide [1] [2] [3] . A minority of patients can develop fulminant disease, which is characterized by acute respiratory distress syndrome (ARDS), sepsis, thromboembolic disease, and multi-system organ failure [4, 5] . Old age and underlying disorders such as arterial hypertension, diabetes mellitus, end-stage kidney disease (ESKD), and compromised immune status are risk factors affecting the morbidity and the mortality of COVID-19 patients [6] [7] [8] . The incidence of COVID-19 in patients with autoimmune disorders was not extensively studied. Also, great controversy exists about the potential role of hydroxychloroquine as protective therapy against COVID-19 in patients with systemic lupus erythematosus (SLE). Hydroxychloroquine was used in COVID-19 therapy due to its in vitro antiviral effects such as inhibition of the glycosylation of host receptors, and endosome acidification, amongst others, preventing likely the viral entry into the host cells (in vivo).

However, the results in human trials were indeed controversial or even discouraging [9] [10] [11] . This report outlines diagnostic and treatment challenges in a young female COVID-19 patient with a flare of SLE.

A 28 year old female with a past medical history of SLE was admitted to the emergency department due to recent onset fever (38.8 o C), persistent cough, fatigue and progressive dyspnea.

Also, she had ESKD due to lupus nephritis Grade VI, and being on maintenance hemodialysis via an arteriovenous fistula for the last three years. The patient's medications integrated hydroxychloroquine and mycophenolic acid as part of her SLE home management. Her mother revealed that she had protected (wearing a surgical mask) contact (one week ago) with one of her sisters who had just recovered from a flu-like illness. Since the endemic wave of COVID-19 had already affected Riyadh, the capital city of Saudi Arabia, we were alerted for a possible SARS-CoV-2 infection; hence, nasopharyngeal swabs were derived urgently and sent for testing.

Moreover, we contacted the family physician requesting that her sister should be tested according to our Ministry of Health recommendations for COVID-19. Consequently, the sister was also tested positive for COVID-19 but was asymptomatic at that time. Hence, in our patient, the time period from symptoms onset to emergency department admission was approximately nine days.

On physical examination decreased breath sounds and crepitations at the lung bases were evident. Her saturation of peripheral oxygen (SpO 2 ) was 88%, on room air, and she had minor respiratory distress. She received 5 liters of oxygen via a nasal cannula. Thereafter, the patient desaturated further (SpO 2: 75%) and developed a picture of septic shock. Therefore, she was intubated and resuscitated by the intravenous administration of 500 ml of normal saline and low dose of noradrenaline to maintain a mean arterial pressure of 70 mm Hg. Electrocardiogram, cardiac enzymes, and echocardiography were normal. Laboratory findings were normal apart from lymphocytopenia (0.59×10 /l, normal: 1.1-3.2 ×10 /l), and increased C-reactive protein infections were negative. We continued her usual maintenance hemodialysis regime and steroid therapy. Oxygen supportive care was discontinued on day-10, and the methylprednisolone was tapered down to 60 mg per day (1mg/kg/day). RT-PCR test for COVID-19 and repeated microbiology tests were negative on day-17. The patient refused any follow-up testing, thus she was discharged to home isolation on day-19, on maintenance oral steroid therapy, and she is thereafter followed-up by her family physician.

In this case-report, a puzzling clinical scenario is encountered. Our patient had COVID-19 pneumonia and a flare of SLE. Her presenting symptoms of fever, cough, dyspnea, hypoxia, and J o u r n a l P r e -p r o o f 6 lung crepitations can be observed both in lupus and COVID-19 pneumonitis [2] [3] [4] [5] [6] [7] [8] [16] [17] [18] [19] .

Moreover, lymhocytopenia can be a hallmark feature in both disorders [4] [5] [6] 20] . Apart from lymphocytopenia, other hematologic abnormalities including hemolytic anemia, leukopenia, and thrombocytopenia are included in the 2019 classification criteria for SLE by the American College of Rheumatology [20] . However, the aforementioned laboratory findings were not evident in our patient. Also, lupus pneumonitis could exhibit non-specific radiography and histology findings. Chest X-rays could demonstrate unilateral or bilateral infiltrates; while chest CT scans could depict ground-glass opacities. Findings on histology include alveolar wall damage, inflammatory cell infiltrates, edema, hemorrhage and necrosis [16] [17] [18] [19] . There is a significant overlap of findings between lupus and COVID-19 pneumonitis, and thus confusion may arise when trying to establish a diagnosis of lupus pneumonitis during the COVID-19

pandemic [16-19, 21, 22] . SLE patients with serious viral pneumonitis can be treated by the administration of steroids [23, 24] . However, our COVID-19 patient with SLE had life-threatening features such as rapidly evolving septic shock and ARDS [2] [3] [4] [5] [6] [7] [8] , which were not documented in previous reports [24] .

ESKD might have at least partially contributed to the severity of the clinical picture, although not affecting unfavorably the outcome in our case [2] [3] [4] [5] [6] [7] [8] . Moreover, the standardized hemodialysis sessions along with the administration of other therapies, and the supportive ICU care may also contributed to the improvement of the patient's oxygenation. Antiviral agents such as remdesivir along with immunomodulatory therapies such as convalescent plasma transfusions, the new monoclonal antibody against interleukin-6 (tocilizumab), and plasma exchange showed promise in the treatment of COVID-19 but remain largely empiric [25] [26] [27] [28] [29] .

The administration of steroids was not recommended in COVID-19, until recently, when the J o u r n a l P r e -p r o o f results of the beneficial role of low-dose dexamethasone therapy were reported in the RECOVERY trial [30] . In contrast, other recently published data showed no effect on 28-day mortality in critically ill COVID-19 patients after the administration of methylprednisolone (METCOVID trial), although patients over 60 years had a lower mortality in a subgroup analysis [31] . In our study, steroids were administered due to the flare of lupus in a young female patient.

We are uncertain whether methylprednisolone mitigated as well the cytokine storm related to COVID-19 [27-29, 32, 33] ; however, given the severity of our patient's clinical picture it might have helped. The putative beneficial effect of steroids on viral pneumonitis was previously advocated in critically ill patients with Middle East Respiratory Syndrome [34] . This remains to be further studied in critically ill patients with COVID-19 along with the potential sequela of the administration of steroid therapy such as delaying of the viral clearance, and increasing the rate of secondary bacterial infections [6] [7] [8] .

The most common signs and symptoms of lupus pneumonitis are fever, cough with lung crepitations and ensuing hypoxemia, which were also observed in our patient with SLE. Several pulmonary manifestations of SLE such as pleural and lung parenchymal involvement, pulmonary hypertension, diffuse alveolar hemorrhage, and thromboembolic disease, amongst others, are well documented [16] [17] [18] [19] [20] . However, lupus pneumonitis occurs only in a minority (1-4%) of SLE patients and carries a poor prognosis; while its therapy is still empiric. The basis of treatment is the administration of prednisone (1-1.5 mg/kg/day), and if there is no response, intravenous methylprednisolone (1g/day) can be added for three days [16] [17] [18] [19] [20] . The administration of steroid therapy, early in the course of lupus pneumonitis, is important due to its high mortality rate. If steroid therapy fails, other immunosuppressive or cytotoxic agents can be used. Fortunately, our patient responded favorably to the administration of steroid therapy.

Notably, this case-report underlines another trending controversy: the putative protective action of hydroxychloroquine in COVID-19. Recent data from the COVID-19 Global Rheumatology Alliance Registry recorded nineteen patients suffering from SLE out of the one hundred and ten rheumatologic patients who were diagnosed with COVID- 19 [35] . Other studies provided evidence that the administration of hydroxychloroquine was not protective against COVID-19, which is in accordance with our current observations [36].

This case-report, albeit its many limitations that prevent its generalizability, carries important messages. Patients with SLE may be affected by COVID-19 despite the administration of hydroxychloroquine. The diagnostic dilemmas and the therapeutic challenges should be carefully processed due to the overlapping clinical, imaging, and laboratory findings between lupus and COVID-19 pneumonitis. In conclusion, the administration of steroids may have a beneficial effect on suppressing both the flare of SLE and the COVID-19 associated hyperinflammation.

Further large prospective studies are required to confirm or refute the present findings. 

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