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Positive Anti-SSA/Ro Antibody in a Woman with SARS-Cov-2 Infection Using Immunophenotyping: a Case Report

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Positive Anti-SSA/Ro Antibody in a Woman with SARS-Cov-2 Infection Using Immunophenotyping: a Case Report medicina Case Report Positive Anti-SSA/Ro Antibody in a Woman with SARS-CoV-2 Infection Using Immunophenotyping: A Case Report 1, 2, 3 2,4 5 Po-I Huang y, Ting-Chun Lin y, Feng-Cheng Liu , Yi-Jung Ho , Jeng-Wei Lu and Te-Yu Lin 6,* 1 School of Medicine, National Defense Medical Center, Taipei 114, Taiwan; [email protected] 2 School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan; [email protected] 3 Rheumatology/Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan; [email protected] 4 Graduate Institute of Life Science, National Defense Medical Center, Taipei 114, Taiwan; [email protected] 5 Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; [email protected] 6 Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan * Correspondence: [email protected]; Tel.: +886-2-87927257 These authors contributed equally to this work. y Received: 27 August 2020; Accepted: 1 October 2020; Published: 5 October 2020 Abstract: The clinical spectrum of novel coronavirus infection appears to be wide, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia, with respiratory failure and even death. Autoantibodies, especially antiphospholipid antibodies, can occur in severe infections. Other autoantibodies are seldom reported. Here, a 60-year-old female patient without dry-mouth symptoms detected positive for anti-60 kDa SSA/Ro antibodies on day 43 after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To investigate this unique clinical case of SARS-CoV-2 infection, immunological characteristics of this case were detected by using flow cytometry and were compared to the other three groups of patients—health subjects, 2019 novel coronavirus disease (COVID-19) recovery patients, and Sjögren’s syndrome (SS) patients. Monitoring the autoantibody level and the development of subsequently related autoimmune diseases are warranted after SARS-CoV-2 infection. Keywords: COVID-19; SARS-CoV-2; Sjögren’s syndrome; autoimmune; immunophenotyping 1. Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is spreading at an alarming rate worldwide. Clinical manifestations include fever, cough, shortness of breath, sore throat, myalgia, arthralgia, headache, rhinorrhea, nausea, vomiting, diarrhea, and olfactory and gustatory dysfunctions. Autoantibodies (particularly antiphospholipid antibodies) are commonly encountered in cases of severe infection [1]. In autoimmune diseases, anti-SSA/Ro antibodies are the most common autoantibodies whose pathological role are still controversial. Anti-SSA/Ro antibodies were frequently observed in association with Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), subacute cutaneous lupus erythematosus (SCLE), neonatal lupus erythematosus (NLE), systemic sclerosis (SSc), polymyositis (PM), dermatomyositis (DM), primary biliary cirrhosis (PBC), and type 1 autoimmune hepatitis (AIH-1). In particular, Medicina 2020, 56, 521; doi:10.3390/medicina56100521 www.mdpi.com/journal/medicina Medicina 2020, 56, 521 2 of 11 the incidence of anti-SSA/Ro positive was 70–100% in SS patients and 40–90% in SLE patients [2]. Autoimmune characteristics exist at the recovery stage of some patients with severe and critical cases of the new 2019 novel coronavirus disease (COVID-19). Among twenty COVID-19 subjects, the prevalence of anti-52 kDa or anti-60 kDa SSA/Ro antibodies were 20% and 25%, respectively [3]. SARS-CoV-2 infection also had correlation with rheumatic disease [4]. However, other autoantibodies are seldom reported. In this case report, we described a female patient without dry-mouth symptom who developed positive anti-60 kDa SSA/Ro antibody at 43 days after SARS-CoV-2 infection. For this patient, we reviewed the previous medical history of this case in the hospital and conducted patient consultation. Therefore, we further ruled out the possibility of other autoimmune diseases. Comparisons of immunological characteristics between patients with this case, health subjects, COVID-19 recovery patients and SS patients were conducted to discuss this unique clinical presentation of SARS-CoV-2 infection. 2. Case Report A 60-year-old female had a history of hypertensive cardiovascular disease with regular follow up. The case departed Taiwan on 2 January 2020, for a trip to the Czech Republic and New York. On 10 March 2020, she presented with fever, dry cough, diarrhea, and throat pain. The case returned to Taiwan on 16 March 2020, at which time she was still suffering from coughing. Upon arrival at our emergency department, she was admitted to the isolation ward. A physical examination performed on admission showed bilateral crackles. The initial laboratory results were as follows: (1) white cell count, 4.04 103 cell/mm3; (2) absolute neutrophil count, 3.06 103 cell/mm3; (3) absolute lymphocyte × × count, 0.69 103 cell/mm3; (4) hemoglobin levels, 13.4 g/dL; (5) platelets, 149 103 cell/mm3; × × (6) Ferritin, 707.9 µg/L; (7) C-reactive protein, 5.77 mg/dL. Chest radiographs showed increased infiltration over bilateral lower lung fields (Figure1A). Chest computed tomography scans revealed diffuse ground-glass opacities throughout both lungs. Throat swabs obtained on 17 March 2020, tested positive for SARS-CoV-2. On 19 March 2020, the case was transferred to the intensive care unit on account of respiratory failure. Endotracheal insertion was performed until 15 April 2020, at which time tracheostomy was done due to difficulties in weaning from the ventilator. Besides, the patient received hydroxychloroquine plus with azithromycin treatment from 16 March to 6 April. According to Taiwan Centers for Disease Control (CDC) regulations, three consecutive samples of throat swab returned negative results for SARS-CoV-2, and the case does not require isolation measures. Although the results were negative for SARS-CoV-2, the case still continued to suffer from intermittent fever. (Figure1B). Following a complete fever workup, the autoimmune disease survey was performed, the case presented anti-60 kDa SSA/Ro antibodies, which is an important criterion for diagnosis with SS, an autoimmune disease. The clinical condition improved gradually under supporting care, and the case recovered well and was discharged on 18 May 2020 (Figure1C). This study was approved by the Institutional Review Board (IRB) of Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, and complied with guidelines (IRB No. 2-106-05-001, date of approval 26 January 2020; Patient informed consent No. 2-106-05-001. Medicina 2020, 56, 521 3 of 11 Medicina 2020, 56, x FOR PEER REVIEW 3 of 9 FigureFigure 1. 1. TheThe progress progress of of the the disease disease and and the the course course of of clinical clinical treatment. treatment. (A (A) )Computed Computed tomography tomography (CT)(CT) of of the the chest. chest. The The cross cross-section-section and and longitudinal longitudinal-section-section of of CT CT revealed revealed diffuse diffuse ground ground-glass-glass opacitiesopacities throughout throughout both both lungs lungs on on 17 17 March March, 2020 2020,, and and recovered recovered on on 23 23 April April, 2020. 2020. ( (BB)) The The temperaturetemperature recordrecord during during the the whole whole hospitalized hospitali period.zed period. The blue The arrow blue means arrow severe mean acutes severe respiratory acute respiratorysyndrome coronavirussyndrome coronavirus 2 (SARS-CoV-2) 2 (SARS (-). The-CoV red-2 dotted) (-). The frame red means dotted a periodframe ofmean intermittents a period fever. of intermittent(C) The disease fever. progression (C) The disease of the case. progression The gray of line the means case. theThe total gray disease line mean progressions the total of thedisease case. progressionThe hollow of arrow the case. points The out hollow the time arrow points point froms out the the beginning time points symptoms, from the SARS-CoV-2 beginning symptoms, positive to SARSnegative,-CoV and-2 positive the level to of anti-Ro.negative, The and yellow the level arrow of means anti-Ro. a period The ofyellow intermittent arrow fever.means The a period green lineof intermittentmeans the hospitalization fever. The green until line discharge. means the The hospitalization green arrow meansuntil discharge. the medical The treatments green arrow of the mean case.s the medical treatments of the case. Comparative analysis of the case was conducted versus a group of patients who had recovered fromComparative SARS-CoV-2 analysis infection of withoutthe case positivewas conducted anti-60 versus kDa SSA a group/Ro antibody of patients (recovery who had group, recoveredn = 4), frompatients SARS diagnosed-CoV-2 infection with SS without (n = 4), positive and healthy anti- volunteer60 kDa SSA/Ro (healthy antibody control (recovery group, n group,= 4). Forn = the4), patientsrecovery diagno group,sed there with are SS two(n = males,4), and aged healthy 22 andvolunteer 66 years (healthy old; andcontrol two group, females, n = aged 4). For 60 andthe recovery28 years old,group, who there had are mild two symptoms males, aged of COVID-19, 22 and 66 years and who old; haveand two received females, hydroxychloroquine aged 60 and 28 years plus old,with
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