Unusual Myositis of the Temporalis Muscle Occurring with Acute Covid-19

Background. SARS-CoV-2 infection can be accompanied by neuromuscular disorders. Rhabdomyolysis and Guillain-Barre syndrome have been described repeatedly. There are case reports of inflammatory myopathies manifesting during COVID-19, presenting as dermatomyositis, polymyositis or immune-mediated necrotizing myopathy, with dermatomyositis-like presentations most commonly reported. Larger cases series are from postmortem examinations of COVID-19 patients, where variable inflammatory pathology of the skeletal muscle has been found frequently but without local detection of the actual virus. Thus, autoimmune mechanisms or the systemic interferon response are discussed as causes. We report a case of focal inflammatory myopathy with perimysial pathology of the temporalis muscle occurring with acute, but mild COVID-19. Methods. Case report of clinical observations, cranial MRI, histopathological, and laboratory findings. 3T cranial MRI was performed with gadolinium contrast. Open temporalis muscle biopsy was performed. The sample underwent standard cryohistological studies as well as immunohistochemistry with antibodies against MHC-I and II, CD3, CD4, CD19, CD68, anti-MAC, p62 and MxA. Testing for auto-antibodies was based on immunoblots or ELISA. RT-PCR for SARS-CoV-2 was run with RNA extracted from cryopreserved muscle. Results. A Caucasian woman in her 60s with no history of autoimmune or muscle complaints developed swelling and pain of the right jaw musculature five days after testing positive for SARS-CoV-2 due to respiratory tract symptoms. In addition, she experienced trismus, but no further neuromuscular complaints. The course of respiratory tract symptoms stayed mild. She had been vaccinated previously with single shot SARS-CoV-2 vector vaccine. Due to persistent swelling and complaints, giant cells arteritis was excluded by unresponsiveness to five days oral steroids and sonography of the temporal artery. Cranial MRI was performed nearly four weeks after the SARS-CoV-2 infection and showed marked swelling and oedema of the temporalis muscle. Its biopsy showed numerous CD68 and acid phosphatase positive cells infiltrating from perimysial perivascular foci towards the endomysium with perimysial damage but little damage of adjacent, perifascicular muscle fibres. Muscle fibres did not react with anti-MHC-II, anti-MAC or -MxA. Capillaries did not react with anti-MAC or -MxA. SARS-CoV-2 RNA was not detected in muscle tissue. Serum creatine kinase was not elevated in the subacute phase. Slightly elevated ANA titre led to detection of autoantibodies against proliferating cell nuclear antigen (PCNA). No pathological results for other autoantibodies, including myositis-specific antibodies and anti-ds-DNA, were found in blood. Neither were antibodies against hepatitis C and B viruses. Retesting 15 weeks after infection, anti-PCNA immunoblot was still positive, but ELISA did not indicate a pathologic titre. The swelling, myalgia and trismus regressed spontaneously a month after onset, yet the latter still persists at the time of reporting. Conclusion. Our case diverges from the majority of COVID-19 associated my-ositis reports in the unusual location of the focal myositis and the histopathological pattern of predominantly perimysial damage and histiocytic infiltration. It concurs with the literature as no SARS-CoV2 RNA could be detected in the muscle. Anti-PCNA is associated very rarely with myositis. Other associated disorder (systemic lupus erythematosus, chronic viral hepatitis B or C) were not found. Increased levels of autoantibodies are reported in COVID-19 and mostly attributed to loss of self-tolerance during the acute disease phase. Interestingly, the structural protein M of SARS-CoV-2 appears to interact notably with PCNA in infected cells. Still, the causal connection between the myositis and COVID-19 in this case is based on the close temporal association in the absence of alternative, competing explanations from the medical history and findings.

Erythema nodosum -Expanding diagnostic workout in COVID-19 pandemic

Case report Erythema nodosum (EN) is considered a delayed type IV hypersensitivity reaction, triggered by exposure to an antigen, which diagnostic workout is usually challenging. Several conditions have been described as possible causes for EN, including infections, sarcoidosis, pregnancy, neoplasic and inflammatory diseases. Rarely, vaccines such as tetanus, diphtheria, BCG, hepatitis B, human papillomavirus, malaria, rabies, smallpox, typhoid, and cholera have been associated with subsequent EN. We present a 31-year- old leucodermic female with suppurative adenitis, who developed painful erythematous nodules on the pretibial area of the lower limbs. Ten days prior to presentation she had received the first dose of the COVID-19 mRNA-1273 vaccine. Fever, lymphadenopathy, fatigue, weight loss, arthritis, cough, diarrhoea, other organ-specifc symptoms and close contact with tuberculosis were excluded. She was under oral contraception for several years, that was not discontinued. Pregnancy was excluded. No positive signs were detected on physical examination besides the referred nodules. Laboratory tests revealed a normal complete blood count, erythrocyte sedimentation rate, C-reactive protein, antistreptolysin O titer, renal and hepatic tests. Interferon-gamma release assay was negative. Circulating rheumatoid factor was normal, anti-nuclear, anti-double stranded DNA and anti-neutrophil cytoplasmatic antibodies were negative. Angiotensin converting enzyme and protein electrophoresis were normal. Hepatitis B and C, HIV 1/2 and syphilis serologic profiles were negative. Urinalysis and fecal calprotectin were unremarkable. The patient was treated with naproxen and topic betamethasone dipropionate. Violaceous involution was reported, with complete resolution of the EN lesions over the following month. In the literature, there are rare reports of EN following SARS-COV2 infection and also after COVID-19 vaccination. To our knowledge this is the second report of EN after the COVID-19 mRNA-1273 vaccine. This case highlights the importance of clinical awareness for the possible association of COVID-19 vaccination and EN, adding to the already extensive list of causes included in the etiological investigation of these patients.

Case report of an antimelanoma differentiationassociated protein 5 antibody-associated amyopathic dermatomyositis

Autoantibodies against melanoma differentiation-associated protein 5 (MDA5) associated with dermatomyositis have recently been described in Asians with rapidly progressive respiratory disease. Here we report the case of a middle-aged white woman with anti-MDA5 antibody-associated amyopathic dermatomyositis with interstitial lung disease (ILD), which is stable with minimal immune suppression. A 55-year-old woman was referred to a virtual dermatology clinic during the COVID-19 pandemic suspected of having widespread eczema involving the chest, face, arm and hands on the background of atopy. On direct questioning, she admitted to having constitutional symptoms, exertional dyspnoea, joint pain and symptoms of proximal muscle weakness. On clinical suspicion of possible connective tissue disorder, she was urgently reviewed in the hospital, where she was found to have a photodistributed rash involving cutaneous ulceration and violaceous plaques. Hand examination showed mechanic's hand mimicking hand eczema, ragged nail cuticles and acute tenosynovitis in the left index finger. Her upper and lower limb muscle power was normal and respiratory examination revealed bi-basal fine end-expiratory crepitation. Her repeated biochemical, haematological and muscle enzymes remained normal. Skin biopsy taken from photosensitive rash over the wrist showed hypergranulosis, Civatte body formation, colloid bodies and dyskeratotic keratinocytes, in keeping with severe lichenoid eruption. Superficial dermis showed patchy red-cell extravasation, perivascular chronic infiltration, dermal oedema and serum on the surface, in keeping with ulceration secondary to severe inflammatory processes. There were no eosinophils and eccrine coils were free of inflammation, raising the suspicion of a drug eruption. Her antinuclear antibody and double-stranded DNA were repeatedly negative. Myositisspecific antibody panel was performed owing to a high clinical suspicion of photosensitive dermatoses, both clinically and histologically. Histology revealed positive anti-MDA5 antibodies;repeated positive testing confirmed this. Although lung function was normal, computed tomography revealed evidence of ILD. We made a diagnosis of anti-MDA5 antibodyassociated amyopathic dermatomyositis with ILD. Her malignancy screening was negative. The patient was started on lowdose prednisolone and hydroxychloroquine 200 mg twice daily, with topical steroid applications, which resulted in remarkable clinical improvement. Anti-MDA5 associated dermatomyositis has characteristic cutaneous lesions consisting of skin ulceration and tender palmar papules, mechanic's hands, inflammatory arthritis and rapidly progressive ILD, which is frequently fatal. Although our patient had ILD, she was relatively stable on minimal immunosuppression. It is important for clinicians to have an increased awareness of this disease as it could have a highly variable clinical presentation in the white population.

A beginner's guide to RT-PCR, qPCR and RT-qPCR

The development of the polymerase chain reaction (PCR), for which Kary Mullis received the 1992 Novel Prize in Chemistry, revolutionized molecular biology. At around the time that prize was awarded, research was being carried out by Russel Higuchi which led to the discovery that PCR can be monitored using fluorescent probes, facilitating quantitative real-time PCR (qPCR). In addition, the earlier discovery of reverse transcriptase (in 1970) laid the groundwork for the development of RT-PCR (used in molecular cloning). The latter can be coupled to qPCR, termed RT-qPCR, allowing analysis of gene expression through messenger RNA (mRNA) quantitation. These techniques and their applications have transformed life science research and clinical diagnosis.Copyright © The Authors.

NEUTROPHIL AND MONOCYTE EXTRACELLULAR TRAPS IN THE DIAGNOSIS OF POST-COVID SYNDROME

Post-COVID syndrome (long covid, post COVID-19 condition) is characterized by cognitive and mental disorders, chest and joint pain, impaired sense of smell and taste, as well as by gastrointestinal and cardiac disorders. The diagnosis of post-COVID syndrome is based mainly on the patients' complaints. To date, no optimal diagnostic method has been proposed. The study was aimed to compare the informative value of the indicators obtained during conventional assessment of patients with post-COVID syndrome and the blood levels of neutrophil (NETs) and monocyte (METs) extracellular traps. The study involved neutropils and monocytes collected from 21 patients with post-COVID syndrome aged 18-59. Fluorescence microscopy and the SYBR Green (Evrogen) fluorescent dye for double-stranded DNA were used for enumeration and imaging of extracellular traps. Clinical and laboratory indicators make it impossible to identify the changes specific for post-COVID syndrome. At the same time, post-COVID syndrome is characterized by inflammation in the vascular endothelium. The filamentous forms of NETs found in blood are a laboratory feature of such aseptic inflammation. The filamentous forms of NETs have been detected only in those patients who have a history of mild to severe СOVID-19, while the filamentous forms of METs have been found in patients having a history of severe infection. The findings show that the detection of the filamentous forms of NETs and METs in blood is the most informative diagnostic feature of post-COVID syndrome.

A case of morphea following the inactivated COVID-19 vaccine

Background: The emergence of the coronavirus disease (COVID-19) prompted pharmaceutical companies to develop effective vaccines to address the problem. While studies prove the vaccines are safe, rare systemic side effects remain possible. All types can cause various vaccine-related adverse reactions which are continuously being monitored. This paper aims to highlight new data on immunologic reactions to COVID-19 vaccines. Morphea demonstrated after COVID-19 vaccination is rare. Herein, we report a case of morphea that was most likely triggered by the immune response against inactivated COVID-19 vaccine. Method(s): A case of morphea was reviewed at the clinic in a tertiary hospital in the Philippines. Result(s): A 48 year old Japanese male had no underlying co-morbidities and no previous COVID-19 infection. He had his first dose of inactivated COVID-19 vaccine, coronaVac (sinovac) with no untoward reactions. After a month, he had his second dose. One week later, the patient started to have a red plaque on his upper back, palpable, tender on palpation and pruritic. Review of systems was unremarkable. The patient denied any insect bites or skin trauma. No medications applied or taken. No known allergies to food, medications or vaccines. He is a 32 pack years smoker. No family history of any autoimmune diseases. In five months, the skin lesion insidiously progressed, thickened and now spreading to the left side of the back. The patient sought consult with a dermatologist and rheumatologist. Physical examination revealed thickened skin and subcutaneous tissue on the upper back with post-inflammatory hyperpigmentation. Work-up showed normal complete blood count, normal chest x-ray, non-reactive Hepatitis B antigen. Antinuclear antibody (ANA) was positive with 1:80 titer and nuclear speckled pattern. Anti-double stranded DNA (anti-dsDNA), anti-smith, antinuclear ribonucleoprotein (anti-RNP), anti-SSA, anti-SSB and anti-Jo- 1 were all negative. The patient's skin biopsy to the reticular dermis showed findings that are consistent with Morphea. The patient was then started on Methotrexate. Conclusion(s): People should be educated about the possible outcomes of COVID-19 vaccines. One of these are immune-related diseases, such as morphea. The underlying mechanism of morphea is multifactorial but one hypothesis highlighted that the spike glycoprotein from vaccination drives these skin reactions. Other studies demonstrated molecular mimicry to viral epitopes. Discussing this cutaneous manifestation secondary to COVID-19 vaccine stressed the importance of this clinical condition, in order to provide a proper diagnosis and therapeutic management. Although there are novel case reports of morphea induced by COVID-19 mRNA vaccine, inactivated COVID-19 vaccine-related morphea has not been reported yet.

CYSTIC LUNG DISEASE IN A YOUNG MALE WITH SYSTEMIC LUPUS ERYTHEMATOSUS

SESSION TITLE: Challenges in Cystic Fibrosis Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Pulmonary involvement in Systemic Lupus Erythematosus (SLE) is seen in 30-50% of patients (most commonly Nonspecific Interstitial Pneumonitis) but cystic lung disease is extremely rare (1). Lymphoid interstitial pneumonia (LIP) is an inflammatory lung disease that is characterized by infiltration of lymphocytes and plasma cells (2), and associated with lung cysts. Oftentimes, it is associated with HIV, lymphoma, and primary Sjogren's Syndrome (SS) (2), however there are rare reports of LIP associated with SLE (1). We present a case of a young male with incidental lung cysts who was found to have a new diagnosis of SLE. CASE PRESENTATION: A 24-year-old male with a past medical history of premature birth at 5 months and prior mild COVID-19 infection presented with 3 weeks of abdominal pain, nausea, vomiting, fever, and unintentional 15-pound weight loss. He endorsed dry mouth, frequent cavities, and a new rash involving his chest, face, and lower extremities. Physical exam was significant for malar rash and dry mucous membranes. Labs revealed pancytopenia, sedimentation rate 61 mm/hour and C-reactive protein 5.54 mg/L. Computed tomography (CT) of the chest showed several thin-walled cysts in all bilateral lung lobes (predominant in right upper lobe) and bilateral axillary lymph nodes [Figure 1]. CT abdomen and pelvis was unremarkable. Autoimmune work-up resulted in a positive antinuclear antibody >1:1280, double stranded DNA antibody elevated at 34, elevated SSA and SSB antibodies (>8.0 and 1.4 respectively), and decreased Complement 3 (59.5 mg/dl) and 4 (10.1 mg/dl) levels. Peripheral smear, right axillary lymph node and bone marrow biopsies were negative for malignancy. He was started on prednisone and Plaquenil with symptomatic improvement. There is high suspicion of LIP given the clinical and radiological findings. He will follow up in clinic to obtain PFTs and schedule a lung biopsy. DISCUSSION: Interstitial lung disease in SLE presents in middle-aged patients at a later part of their disease course, with a female preponderance (2,3). An initial presentation of SLE and secondary SS in a young male and associated cystic lung disease is rare. The suspicion for LIP in association with SLE is high in our patient given variable size and distribution of lung cysts and coexisting secondary Sjogren's syndrome, although no ground glass or nodular opacities were found on CT chest as reported in typical LIP (3). Though this patient has no pulmonary symptoms, cysts/LIP in SLE tend to progress and have a high incidence of developing lymphomas, gammaglobulinemia and amyloidosis (2,3). CONCLUSIONS: It is important to establish a histopathological diagnosis and obtain baseline PFTs to monitor pulmonary disease manifestations. In addition to controlling the primary disease with antirheumatic drugs, steroids have been found to be useful in acute pulmonary flares (2). Reference #1: Maeda R, Isowa N, Miura H, Tokuyasu H. Systemic lupus erythematosus with multiple lung cysts. Interact Cardiovasc Thorac Surg. 2009 Jun;8(6):701-2. doi: 10.1510/icvts.2008.200055. Epub 2009 Mar 12. PMID: 19282324. Reference #2: Yood RA, Steigman DM, Gill LR. Lymphocytic interstitial pneumonitis in a patient with systemic lupus erythematosus. Lupus. 1995 Apr;4(2):161-3. doi: 10.1177/096120339500400217. PMID: 7795624. Reference #3: Filipek MS, Thompson ME, Wang PL, Gosselin MV, L Primack S. Lymphocytic interstitial pneumonitis in a patient with systemic lupus erythematosus: radiographic and high-resolution CT findings. J Thorac Imaging. 2004 Jul;19(3):200-3. doi: 10.1097/01.rti.0000099464.94973.51. PMID: 15273618. DISCLOSURES: No relevant relationships by Matthew Fain No relevant relationships by Christina Fanous No relevant relationships by Rathnavali Katragadda No relevant relationships by CHRISELYN PALMA

NEW-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS AND STEVEN JOHNSONS SYNDROME WITH SEVERE ARDS HERALDED BY POST-COVID-19 INFECTION MULTISYSTEM INFLAMMATORY SYNDROME IN AN ADULT (MIS-A)

SESSION TITLE: Autoimmune Diseases Gone Wild: Rare Cases of Pulmonary Manifestations SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Post-Covid-19 Multisystem Inflammatory Syndrome (MIS) is a severe hyperinflammatory syndrome associated with either the acute or recovery phase of covid-19 infection affecting multiple organ systems requiring hospitalization. This syndrome has been described in both children (MIS-C) and adults (MIS-A). Several case reports and systematic reviews have reported an association between post-covid-19 MIS-A and several autoimmune diseases. CASE PRESENTATION: We herein report a case of a 27-year-old female with no known chronic medical condition and a non-contributory family history who was diagnosed with post-covid-19 multisystem inflammatory syndrome in adults (MIS-A). She presented with generalized partial thickness erythematous skin ulcerations with tender blistering and painful erosion of her mucus membranes (oral and vaginal mucosa). This was diagnosed as Steven Johnsons syndrome. She was pulsed with intravenous methylprednisone. During this therapy, she progressed to severe acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (fig 1). Bronchoscopy revealed mild pulmonary hemorrhage fig 2a&b). Serological testing heralded a new onset systemic lupus erythematosus in light of positive antinuclear antibodies, anti Ds DNA and anti Smith antibodies. Her course was complicated by significant proteinuria and an active renal cast suggestive of lupus nephritis. This necessitated further treatment for active lupus. She was successfully extubated and discharged home. DISCUSSION: We arrived at the diagnosis of post-covid-19 multisystem inflammatory syndrome in adults (MIS-A) in light of her presenting with fever, hypotension, persistent sinus tachycardia and new onset atrial fibrillation), acute pancreatitis, acute kidney injury, elevation in transaminases, new onset skin rash, elevated inflammatory markers and a recent history of positive SARS-CoV-2 infection. Covid-19 has been reported to induce wide spread vasculitis resulting in MIS-A or MIS-C by triggering type 3 hypersensitivity (1). Also, multiple case reports and systemic reviews have reported a direct association between MIS-A and several autoimmune diseases including SLE, SJS (2). The patient recovered with high dose corticosteroid and supportive therapy indicating her severe ARDS was most likely due associated to SJS, SLE and MIS-A. Clinicians should also keep in mind that SARS-CoV-2 PCR swab may be negative at the time patient presents with symptoms of MIS-A as the infection might have occurred about 4-5weeks prior just as in our patient(3) CONCLUSIONS: We cannot underscore enough the importance of clinicians having a high index of suspicion for this syndrome in patients with acute or recent covid-19 infection, with or without a positive PCR covid-19 test. Early involvement of a multidisciplinary approach and appropriate management is essential to mitigate morbidity and mortality in these patients. Reference #1: Roncati L, Ligabue G, Fabbiani L, Malagoli C, Gallo G, Lusenti B, et al. Type 3 hypersensitivity in COVID-19 vasculitis. Clin Immunol Orlando Fla. 2020 Aug;217:108487. Reference #2: Gracia-Ramos AE, Martin-Nares E, Hernández-Molina G. New Onset of Autoimmune Diseases Following COVID-19 Diagnosis. Cells [Internet]. 2021 Dec 20 [cited 2022 Mar 22];10(12):3592. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700122/ Reference #3: Morris SB. Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection — United Kingdom and United States, March–August 2020. MMWR Morb Mortal Wkly Rep [Internet]. 2020 [cited 2022 Mar 22];69. Available from: https://www.cdc.gov/mmwr/volumes/69/wr/mm6940e1.htm DISCLOSURES: No relevant relationships by Isaac Ikwu No relevant relationships by Anthony Lyonga Ngonge No relevant relationships by Alem Mehari No relevant relationships by Noordeep Panesar no disclosure on file for Vis al Poddar;No relevant relationships by Emnet Yibeltal

USE of TELEMEDICINE for FOLLOW-UP of LUPUS NEPHRITIS in the COVID-19 OUTBREAK: ONE-YEAR, PRAGMATIC RANDOMISED CONTROLLED TRIAL

Background: Patients with systemic lupus erythematosus (SLE) are at increased risk of severe COVID-19 due to the underlying disease, comorbidities and use of immuno-suppressants (IS). An alternative option would be to adopt telemedicine (TM) to maintain medical care while minimizing exposure. Despite being widely adopted during the pandemic, the evidence supporting the use of TM in rheumatology has been limited. Objectives: We primarily aimed to evaluate the effectiveness to maintain disease activity control using TM delivered care compared to conventional in-person follow-up in patients with lupus nephritis (LN). The secondary objectives were to compare the patient reported outcomes, safety and cost-of-illness from the patient's perspective between the 2 modes of health care delivery. Methods: This was a 1-year, single-center, RCT conducted at a regional hospital in Hong Kong. From May 2020, consecutive adult patients with a SLE according to the 2019 EULAR/ACR classifcation criteria followed up at the LN clinic were invited to participate in the study. Participants were randomized 1:1 to either TM (TM group) or standard FU (SF group). Patients randomized to receive TM FU were scheduled for a video consultation via a commerical software ZOOM. Patients in the SF group received standard in-person outpatient care. SLE disease activity at each consultation was assessed by SLEDAI-2k and physician global assessment (PGA). Results: A total of 144 patients with LN were randomized and 3 patients self-withdrew from the study. The mean age was 44.5±11.4 years and the median time from diagnosis to randomization was 168 months (range: 1-528). Most of the patients had class III, IV or V LN (87.2%) and were on prednisolone (89.4%, median dose 5mg daily). Many of them (68.1%) were on IS. While 66.0% of the patients were in lupus low disease activity state (LLDAS), none had disease remission. There were no baseline differences, including demographics, SLEDAI-2k (TM: 3.8±2.3, SF: 3.2±2.2, p=0.13, PGA (TM: 6.2±6.5, SF: 4.6±5.9, p=0.13) and SLE damage index (TM: 1.1±1.3, SF: 0.8±1.1, p=0.10), between the 2 groups. At one year, 80.0% and 80.2% of the patients in the TM group and SF group were in LLDAS or remission respectively. SLE disease activity indices including SLEDAI-2k, PGA, proteinuria amount and serum anti-ds-DNA level remained similar between the 2 groups. Within the study period, 28 (40%) patients in the TM group and 21 (29.6%) patients in the SF group had disease fare (p=0.20). There were no differences in the SF-36, lupusQoL and HADS scores between the 2 groups at the end of the study. The overall patient satisfaction score was higher in the TM group with a signifcantly shorter waiting time before seeing doctors. At the end of the study, 67.9% of the overall participants agreed to (versus 15.0% who did not agree to) use TM as a mode of future FU. The mean indirect costs of illness (HKD26,681 vs HKD12,016, p=0.20) and the out-of-pocket costs for health care services were similar between the 2 groups (TM: HKD13,547 vs SF: HKD12,297, p=0.83) in one year. The total number of FU was similar (TM: 6.0±2.0, SF: 5.7±1.7, p=0.40). However, signifcantly more patients in the TM group (29/70, 41.4% vs 4/71, 5.6%;p<0.01) requested change mode of FU. The proportion of patients requiring hospitalization during the study period was also higher in the TM group (TM: 23/70, 32.9% vs 11/71, 15.5%;p=0.02). After adjusting for age and pred-nisolone dosage, not being in LLDAS at baseline was the predictor of hospitalization (OR 3.4, 95%CI 1.20-9.65). None of the participants was tested positive for COVID-19. Conclusion: TM FU resulted in similar 1-year disease activity control and better satisfaction in patients with LN compared to standard care. However, a signifcant proportion of patients cared by TM required in-person visits or were hospitalized. The results of the study suggest that TM delivered care could help minimizing exposure to COVID-19, but it needs to be complemented by physical visits, particularly in those with unstable d sease.

HIGH PREVALENCE of SERUM AUTOANTIBODIES in SEVERELY ILL COVID-19 PATIENTS HOSPITALIZED in the INTENSIVE CARE UNIT

Background: Coronavirus Disease-19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by a wide range of clinical manifestations 1. Although COVID-19 was initially considered a respiratory infection, it was shortly recognized as a multisystemic disorder associated with heightened infammatory responses, including autoimmune phenomena 1. The presence of autoantibodies (AAbs) has been described in COVID-19 patients, highlighting the state of immune dysregulation in COVID-19 1. The clinical signifcance of AAbs, however, is still elusive. Objectives: To assess the prevalence of AAbs in critically ill, mechanically ventilated COVID-19 patients admitted to the intensive care unit (ICU) and investigate whether AAbs influence the clinical outcome of these patients. Methods: The current study evaluated prospectively from March 8th, 2021 to May 10th, 2021 the presence of AAbs against nuclear antigens (ANA), extracta-ble nuclear antigens (ENA), neutrophil cytoplasmic antigens (ANCA), cyclic cit-rullinated peptides (anti-CCP), double stranded-DNA (anti-dsDNA), cardiolipin (anti-CL), β2-glycoprotein-I (anti-β2-GPI), thyroid peroxidase (anti-TPO), and thyroglobulin (anti-TG) in critically ill COVID-19 patients upon admission in the ICU (n=217). Samples from 60 COVID-19 patients that were available 15 days after ICU admission were further analyzed for the evaluation of de novo AAbs production. Serum samples of age and sex matched healthy individuals before the COVID-19 pandemic were used as a control group (n=117). Results: COVID-19 patients treated in ICU had more commonly at least one AAb compared to age and sex matched controls (174/217, 80.2% vs 73/217, 62,4%, p< 0,001). More specifcally, COVID-19 patients expressed more frequently ANAs (48.4% vs 21.4%, p<0.001), anti-dsDNA (5.1% vs 0%, p=0.01), anti-CCP (8.3% vs 1.7%, p=0.014) and anti-CL IgM AAbs (21.7% vs 9.4%, p=0.005) than controls. The majority of critical COVID-19 patients who were positive for AAbs (144, 82.8%) expressed reactivity in up to three autoantigens with the most prominent being ANA, anti-phospholipid, ANCA and anti-TPO AAbs. AAbs-positive patients demonstrated more robust anti-SARS-CoV-2 humoral responses compared to AAbs-negative patients [detectable anti-SARS-CoV-2 S1-protein IgG antibodies: 150 (86.2%) vs 28 (65.1%), p=0.001;adequate neutralizing activity: 159 (91.4%) vs. 33 (76.7%), p=0.007]. The two groups, however, did not differ in terms of clinicoepidemiologic characteristics or the incidence of death in the ICU. Convalescent COVID-19 patients (n=111) compared to those who died (n=106), did not differ in the prevalence of serum AAbs or antibody responses against SARS-CoV-2. Differences were only shown in clinicolaboratory parameters including patients' age, comorbidities, O2 saturation, infammatory markers, and in-hospi-tal prognostic scores as expected. Paired samples testing (n=60) revealed that 45 patients had at least one newly induced AAb, 28 patients lost at least one reactivity and only 6 patients didn't show any seroconversion. The most common new-onset AAb reactivity was against anti-CL (IgG isotype) (n=21) followed by ANA (n=20), anti-β2-GPI (IgG isotype) (n=11), myositis-related antigens (n=13) and ENAs (n=9);nevertheless, no associations with clinicoepidemiologic features or COVID-19 outcome were revealed. Conclusion: Patients with severe COVID-19 express AAbs more commonly than age and sex matched controls, suggesting that SARS-COV-2 infection may induce a hitherto unknown B-cell autoreactivity. The presence of autoantibodies does not play a role in the outcome of SARS-COV-2 infection. However, further studies are needed to defne their role in future development of systemic autoimmune disorders or the long-COVID syndrome.

EVALUATION of the POTENTIAL INDUCTION of AUTOANTIBODIES after the ANTI-SARS-COV2-VACCINATION in A COHORT of PATIENTS with TRIPLE POSITIVITY for ANTIPHOSPHOLIPID ANTIBODIES

Background: Anti-SARS-CoV2 vaccines showed a good efficacy in prevention of severe COVID-191. Their potential in induction of autoantibodies (abs) has not been well established1. One recent study demonstrated an increase of abs' titre after anti-SARS-CoV2 vaccination only in patients with already pre-existing positivity2. Objectives: To evaluate the potential induction of abs after anti-SARS-CoV2 vaccination in a triple positive antiphospholipid antibodies (aPL) cohort. Methods: 18 subjects were enrolled [M/F= 17/1;median age=52 years;5 Primary Antiphospholipid Syndrome (PAPS), 5 Systemic Lupus Erythematosus (SLE) with associated APS and 8 aPL carriers (1 Behçet Disease, 1 SLE, 4 Undifferentiated Connective Tissue Disease, 2 with no diagnosis of systemic autoimmune disease)]. Serum samples were collected before the first (T0) and at least one month after the second administration (T1) of the anti-SARS-CoV2 vaccine (16 BNT162b2, 1 mRNA-1273, 1 Gam-COVID-Vac). A wide panel of abs were evaluated through routinely methods. Results: None developed any additional sign of autoimmune diseases upon vaccination. Patients majority did not display any new autoantibody posi-tivity (Table 1). Changes were observed in 3 patients: 1) one aPL carrier patient who was antinuclear antibodies (ANA) negative at T0 was found to be ANA positive at T1 [negative anti-double stranded DNA and anti-extractable nuclear antigen (ENA)];this patient was actually ANA positive in her clinical history;2) one aPL carrier patient affected by SLE, who was IgM and IgG aCL and IgG aB2GPI positive at T0, turned positive for IgM and IgA aB2GPI;3) one aPL carrier patient affected by Behçet Disease, who was positive for IgM aCL and for IgM aB2GPI at T0, turned positive for IgA aCL and IgA aB2GPI. All emerging aPL were low titre. None of the patients displayed raising aPL titres from low to medium-high. Conclusion: Anti-SARS-CoV2 vaccination did not induce any clinical signs of autoimmunity in a cohort of patients with triple aPL positivity. Serology for autoantibodies remained stable in the majority of patients. Few patients experienced the emergence of low titre aPL, possibly as an expected inter-assay variation rather than an evolving 'serological fare'.

A RARE CASE of ACUTE INFLAMMATORY DEMYELINATING POLYRADICULOPATHY FOLLOWING the SECOND DOSE of PFIZER COVID-19 VACCINE

Background: We present a case of a 36 year-old female who developed Acute Immune-mediated Demyelinating Polyneuropathy (AIDP) after receiving the second dose of Pfzer COVID-19 vaccine. Objectives: To report a rare auto-immune complication of COIVD-19 vaccination. To educate and inform physicians about the approach to diagnosing AIDP and narrowing down its etiology. Methods: Case report and literature review Results: A 36 year-old female with no signifcant past medical history presented to the hospital with progressive bilateral paresthesia. She started to experience numbness and tingling sensation in her extremities 1 week after receiving the second dose of Pfzer COVID-19 vaccine. Following 5 days of symptoms onset, she was no longer able to hold onto objects and experienced difficulty ambulating without assistance. Physical exam was notable for decreased distal sensation to touch and pain in all 4 limbs, otherwise, the rest of her neurological and musculoskeletal evaluation was normal. MRI-head showed small scattered foci of increased FLAIR signal in the white matter, suggesting an underlying infammatory process. Electromyography (EMG) was performed and showed evidence of acute diffuse sensorimotor neuropathy with mixed axonal and demyelinating features. These results along with the clinical features allowed us to diagnose our patient with Acute Immune-mediated Demyelinating Polyneuropathy (AIDP). Extensive autoimmune workup, including anti-GM1, GD1b, Gq1b, ANA, DS-DNA, RF, CCP, and C/P ANCA, were unremarkable. She had positive anti-Ro atb but did not have any clinical or physical features that would suggest Sjogren's Syndrome. Vitamin levels (B12, folate, thiamine) were found to be normal. Infectious workup of serum and CSF which included hepatitis serologies, Campylobacter jejuni serology, Lyme atb, CMV atb, EBV atb were all negative. The possible etiology of her disease was attributed to Pfzer COVID-19 vaccine given the temporal correlation. She was subsequently treated with 6 cycles of IVIG which resulted in moderate symptomatic improvement. Conclusion: AIDP is an autoimmune-guided infammatory neuropathy which result in axonal degeneration of myelinated nerves [1]. In some extremely rare cases, molecular mimicry following vaccination may lead to this disease [1]. There have been reports of AIDP linked to Johnson & Johnson and AstraZeneca COVID-19 vaccines [2]. Recently, a few cases have also been observed with Pfzer COVID-19 vaccine [2-3]. Interestingly, the majority of these cases occurred after the frst dose of the vaccine, making our case even more peculiar [2]. We report this case as physicians should be made aware that AIDP is a potential complication of COVID-19 vaccination. Given the extreme rarity of these cases, it is also important to note that more common infectious and autoimmune etiology of AIDP should be investigated before attributing any potential causal relationship to COVID-19 vaccines.

DEVELOPMENT of INFLAMMATORY MYOPATHY after COVID-19

Background: It has been more than a year and a half since the WHO announced a pandemic of a new coronavirus infection caused by SARS-CoV-2. The virus belongs to the respiratory group, but it it can damage various organs and tissues of the body. COVID-19 infection is characterized by pathological activation of immunity, violated synthesis of pro-infammatory, immunoregulatory, anti-infammatory cytokines, such as interleukins-1 and-6, tumor necrosis factor α and others. These features contribute to the development of rheumatic diseases and syndromes in people who have had COVID-19. Cellular and humoral immune responses are also of primary importance in the pathogenesis of infammatory myopathies. Objectives: Description of a case of severe dermatomyositis after COVID-19. Methods: The 34-year-old female patient complained of pain and weakness in the proximal muscles of the upper and lower extremities, difficulty swallowing solid and liquid food, rash on the face, neck, chest and arms. In August 2020 she had a mild case of COVID-19. A month later, faky erythematous papules like Gottron's sign appeared on the extensor surfaces of the metacarpophalangeal joints and proximal interphalangeal joints of the hands. Six months later, sore throats, hoarseness of voice, belching of air, choking on solid food and episodes of subfebrility joined. Refux esophagitis, duodenitis was detected by fbrogastroduodenoscopy. After 9 months, there were muscle pains and muscle weakness, erythema on the face, neck and chest, the patient lost 11 kg. She was hospitalized in the rheumatology department with suspected dermatomyositis. Results: On objective examination: proximal myopathy, erythematous rashes on the face, neck, chest, Gottron's erythema on the hands. In the analyses: clinical analysis of blood and urine without pathology, ANA 1:1280, creatinkinase 5370 IU/l, with an increase in dynamics up to 9260 IU/l, CRP 0.03 mg/dl, LDH 1023 IU/l, rheumatoid factor and anti-ds DNA were negative. Nasal regurgitation was detected during radiography of the pharynx with contrast. Instrumental examination revealed no signs of a tumor process. Fibrogastroduodenoscopy-superfcial refux-esophagitis, duodenitis, Chest CT-interstitial pneumonitis, abdominal ultrasound without pathology, ECG-sinus rhythm, normal EOS position, accelerated A-V conduction, echocardiography-minor separation of pericardial leaves (up to 5 mm), colonoscopy-dolichosigma. The patient was diagnosed with idiopathic dermatomyositis of high activity. Because of progressive myopathy and increasing dysphagia, pulse therapy with methylpredniso-lone500 mg for 3 days and rituximab 1000 mg was performed. She also received metipred 48 mg per day orally, methotrexate 15 mg per week subcutaneously and folic acid 5 mg per week. Against the background of therapy, positive dynamics was noted: swallowing normalized, the severity of myopathy decreased, after 10 days CKdecreased to 2049 IU/l. After 6 months during the control examination: there are no skin rashes, muscle strength is restored, CK 300 IU/l. The dose of methylprednisolone is reduced to 10 mg per day, the patient continues injections of methotrexate 15 mg per week. Conclusion: COVID-19 may be a trigger for the development of infammatory myopathy. In this clinical case there are features of the course and therapy of infammatory myopathies in patients after coronavirus infection.

SLE After SARS-COV-2 Infection

SARS-COV-2 infection is often associated with exaggerated immune response, also referred to as a ‘cytokine storm’. There is growing concern that it may be linked to autoimmunity, with many cases of autoimmune diseases either triggered by or related to SARS-COV-2 having been reported, ranging from Guillain-Barre syndrome, Graves’ disease, multiple sclerosis, Kawasaki-like disease. Our patient was a 20-year-old female with a history of hidradenitis who presented with malaise, feet and ankle swelling, asthenia, anorexia, weight loss of 50 Ibs of 4 months. She had COVID pneumonia 7 months prior and was also seen in the ER thrice afterwards for ankle pain and fatigue managed with antibiotics and analgesics. Exam findings included tender bilateral lower extremity edema, diffuse hyperkeratotic and hyperpigmented purpuric rashes and bilateral suppurative axillary swellings. She was admitted for protein-energy malnutrition. Blood work showed WBC 13.5, low Hb 9.3, AST 509, ALT 104, BUN 29, Creatinine 0.9, Protein 7.5, albumin 1.5 (globulin gap of 6). Urine assay showed 3+ proteinuria Hb 3+ with RBC 3-10/hpf, absent nitrite, LE 1+, protein/creatinine ratio was 2949 mg/g. Blood cultures returned negative. US showed trace pericardial effusion and normal kidneys. Infectious workup returned negative for anti-streptolysin O, HIV, hepatitis B and C. Two days after, she developed AMS, fever, tachycardia and neck stiffness concerning for possible meningoencephalitis. CT head was normal. Lumbar puncture was performed. IV vancomycin and piperacillin-tazobactam was started. CSF fluid analysis revealed total protein of 125mg/dl, elevated IgG 79.8, concerning for an underlying inflammatory pathology. EEG was unremarkable. She became oliguric with creatinine and BUN both peaking at 2.6 and 58 respectively. Renal ultrasound revealed medical renal disease. Urine microscopy showed granular cast and no dysmorphic RBCs. ANA, anti-smith SSA, SSB, DS-DNA, RF, smooth muscle, anti-histone, anti-centromere, JO-1 and RNP antibodies were markedly elevated. She was unstable for CT trocar biopsy of the kidney. She subsequently went into cardiac arrest multiple times about a week into admission, before eventually expiring. Though causation was not established in our patient, SARS-COV-2 infection causing exaggerated immune response may unmask SLE or be associated with SLE.

Seronegative Full-House Immune Complex Glomerulonephritis Post-mRNA COVID-19 Vaccination

Immunization with COVID-19 mRNA vaccines has been associated with new-onset and relapse of glomerulonephritis (GN)1,2. We present a case of new onset, seronegative, full-house immune-complex GN after mRNA COVID-19 vaccination. A 24-year-old male with history of idiopathic portal vein thrombosis in childhood, portal hypertension post splenorenal shunt and splenectomy 5 years prior presented with 9 weeks of progressive edema, ascites, and foamy urine. His symptoms started then worsened after his 1st and 2nd doses of the mRNA- 1273 COVID-19 vaccination (Moderna). Cr peaked at 3.04mg/dl (baseline 0.7) and UPCR at 50.52 g/g. Serum albumin 0.9 g/dl. Complements were low. ANA and anti-DS DNA were negative as were other serologies. Infectious work up was also negative. Kidney biopsy showed membranoproliferative pattern of injury on light microscopy with one fibrocellular crescent and without IFTA. IF revealed “full house” staining and EM showed severe subepithelial deposits with subendothelial and mesangial deposits. No tubuloreticular inclusions were present (Figure 1). The patient received cyclophosphamide 750 mg and high dose steroids. One month after treatment, Cr improved to 0.92 and proteinuria fell to 6.05g/g. Complements returned to normal. The high potency of mRNA COVID-19 vaccine can induce a robust immune response which may incite or unmask GNs2. Our patient had a rapid and robust response to immunosuppression. Seronegative full-house immune complex GN may occur after receiving mRNA SARS-CoV-2 vaccination and nephrologists should be aware of potential association. Prompt recognition and treatment may lead to favorable outcomes. (Figure Presented)

CULTURAL BARRIERS AND PANDEMIC RESTRICTIONS RESULT IN A DELAYED DIAGNOSIS OF DRUG INDUCED LUPUS (DIL) AND SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

CASE: A 58-year-old female with a history of hypertension, type 2 diabetes and hyperlipidemia presented with a two- week history of abdominal pain and fevers. Per the patient, family history was unremarkable, and she denied alcohol, tobacco, or recreational drug use. She denied recent travel or sexual activity and had moved to the U.S. in the 1970s from Cambodia. Medications included amlodipine, atorvastatin, dapagliflozin, lisinopril, metformin and sitagliptin. Physical exam was notable for bilateral axillary lymphadenopathy, hepatomegaly, and right sided abdominal tenderness. Laboratory data was notable for microcytic anemia, thrombocytopenia, and elevated transaminases, D-dimer, and C- reactive protein. Urinalysis demonstrated microscopic hematuria and proteinuria. Imaging showed diffuse lymphadenopathy and hepatomegaly. Autoimmune work-up was strongly positive for ANA, anti-histone, and anti DS DNA. Kidney biopsy was suggestive of glomerulonephritis. Liver biopsy was suggestive of drug induced liver injury or autoimmune hepatitis. A diagnosis of DIL and SLE was not reached until additional historical data from the patient's son was provided on hospital day 4;namely that the patient had a 30-lb unintentional weight loss, took unknown herbal supplements and had a daughter who passed away from complications of lupus. IMPACT/DISCUSSION: DIL is a rare adverse reaction to many drugs that generally manifests with mild systemic symptoms such as low-grade fevers, anorexia, and fatigue and rarely involves classic symptoms of SLE such as skin findings and major organ involvement. Notably, DIL can unmask clinically silent SLE and thereby lead to lupus like syndromes. This patient presented with mild symptoms and underwent an extensive workup due to missing key historical data which led to a delayed diagnosis. Due to COVID-19 restrictions on visitation, it was not until hospital day 4 when the patient's son visited that the team became aware of an unintentional 30-lb weight loss, unknown herbal supplement use, and a family history of SLE. The lack of such critical information stemmed from the fact that we did not ask about the use of supplements properly and never revisited it in a different manner. The patient did not share the cause of her daughter's passing as she was unaware of it, which may speak to cultural limitations in sharing health information among family members. It is imperative that as clinicians we constantly revisit the history and diversify our questions. A more complete history would optimize our workup and limit unnecessary testing, including blood draws and painful biopsies, which unfortunately occurred in this patient. CONCLUSION: A thorough history is important to achieving a timely diagnosis and to avoid excessive testing and procedures. Revisiting the history is necessary to finding key information and clinicians should consider incorporating available family members early in the diagnostic work up, especially if the diagnosis is unclear.

Targeting Mycobacterium tuberculosis dUTPase to fight against the TB disease

While the new coronavirus has turned our lives upside down causing millions of deaths, the historically known tuberculosis (TB) disease caused by Mycobacterium tuberculosis (MTB) was responsible for the loss of approximately 1.5 million lives alone in 2021. New anti- TB drugs are in an urgent need. A promising target is dUTPase, an enzyme preventing uracil incorporation into DNA. It is present in all multicellular species and in most microbes. Abolition of its activity potentially leads to DNA double strand breaks and cell death. Therefore, species-specific inhibition of MTB dUTPase may be a successful way of TB disease treatment. Currently no species-specific dUTPase inhibitor exists, but an interaction partner, protein Stl shows significantly different ability to inhibit dUTPase homologues from various species. We use Stl as a model to understand how species- specific differences in dUTPase structure may be harnessed in future inhibitor development. A remarkable species-specific characteristic of MTB dUTPase is a small surface sequence loop playing no direct role in enzyme activity but being essential for mycobacterial survival in a yet unknown way. What is the exact structural background of MTB dUTPase-Stl interaction? For this reason, we have crystallized a complex of MTB dUTPase and a truncated Stl protein mutant. And how the loop sequence may affect the MTB dUTPase protein structure on its own? For this answer, we obtained another X-ray diffraction dataset of a loop-lacking mutant of MTB dUTPase with 1.3 Å resolution. Surprisingly, electron density of the flexible C-terminal “arm” segment of the mutant dUTPase was missing from our dataset, contrary to the already crystallized wildtypeMTB dUTPase structures. We postulate that the loop sequence may restrict conformational flexibility of the dUTPase “arm”, making it more inhibitable by Stl compared to the loop-lacking mutant, as we know from our comparative steady-state enzyme activity inhibition measurements.

Subacute cutaneous lupus erythematosus after COVID-19 vaccination

Numerous cutaneous reactions have been reported secondary to COVID-19 vaccinations. The most commonly reported include local site reactions, delayed large local reactions, urticaria and morbilliform eruptions. Here we report a case of de novo subacute cutaneous lupus erythematosus (SCLE) after COVID-19 immunization. A 56-year-old woman presented with a 3-month history of a rash. The onset was 1 week following the first dose of the AstraZeneca COVID-19 vaccine. She reported lesions characterized by erythema, pruritus and a burning sensation. She also described mouth dryness. Examination revealed scaly annular erythematous plaques on the chest, arms, legs and scalp. Blood results were positive for anti-Ro antibodies and strongly positive for anti-nuclear antibodies (1: 2560 titre). Anti-Smith, anti-centromere and double- stranded DNA antibodies were negative. Skin biopsy revealed the histological appearance of an interface of dermatitis. Direct immunofluorescence was negative. These clinical and histopathological findings are consistent with a diagnosis of SCLE. The patient was treated with hydroxychloroquine, a weaning course of prednisolone, topical steroids and topical tacrolimus. Her hydroxychloroquine dose was 200 mg twice daily for the first 3 months and then increased to 400 mg twice daily. This resulted in an improvement of her presentation although she has yet to achieve complete remission. It has been suggested that enhanced interferon responses with COVID-19 vaccination and interactions of the SARS-CoV-2 spike protein with cytoplasmic RNA-binding proteins could contribute to disease flares in lupus. There are two other recent reports of SCLE developing or being exacerbated by COVID-19 vaccination. More research is required to determine how COVID-19 vaccinations affect patients with autoimmune skin diseases.

DE NOVO DOUBLE GLOMERULOPATHY (MEMBRANOUS NEPHROPATHY, MN AND COLLAPSING FOCAL SEGMENTAL GLOMERULOSCLEROSIS, CFSGS) ASSOCIATED TO POSITIVE MYELOPEROXIDASE-O (MPO) ANTIBODY FOLLOWING PFIZER - BIONTECH MRNA VACCINATION COVID 19

BACKGROUND AND AIMS: In the COVID 19 pandemic era, anti SARS-CoV-2 vaccination showed high efficacy at preventing the infection and its most severe complications. The aim of this report is to describe an unusual double glomerulopathy related to anti SARS-CoV-2 vaccination and the good results obtained with the immunosoppressive treatment. METHOD: An 80-year-old caucasian woman developed a nephrotic syndrome, progressive renal insufficiency and microhematuria. The patient presented a medical history of thrombocytopenic purpura treated and resolved by steroids in 2013, hypothyroidism, hypertension, ischaemic heart disease treated with surgical bypass in 2019 and pacemaker in 2020 for atrial ventricular block. Due to pandemic COVID 19 status, she received two doses of the Pfizer BioNTech mRNA COVID-19 vaccine in March 2021. Two weeks after the second dose her weight increased of 23 kg. The family physician added furosemide to her therapy for generalized edema with no diuretic effect. In April, creatinine was 1.38 mg/dL (versus 0.8 mg/dL 1 year before);urinalysis showed proteinuria (300 mg/dL) and microscopic hematuria;serum total cholesterol level was 218 mg/dL and triglycerides 178 mg/dL;then it was suggested to increase the doses of furosemide. In May 2021, creatinine resulted 2 mg/dL, serum albumin 2 g/dL, and urinalysis confirmed proteinuria and microscopic hematuria;proteinuria was 10 g/day. Abdomen ultrasound showed normal liver, kidneys and spleen, not ascites. Lower limb eco-Doppler showed right superficial femoral artery stenosis of 60% and absence of venous thrombosis. The physical examination evidenced anasarca. The patients were admitted to the nephrology unit;hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus antigen and antibody were negative. Both complement C3 and C4 levels resulted within the normal range. Cryoglobulins were absent. Urinary Bence Jones, antinuclear antibody (ANA), anti-extractable nuclear antigen (ENA), anti-double stranded DNA (nDNA) antibodies were negative. Antineutrophil cytoplasm antibodies (ANCA) were 1:2560 with Perinuclear pattern and anti-MPO positivity (716 UA/mL);anti-proteinase-3 antibodies (PR3) were negative. Antiphosholipase A2 receptor antibody (PLA2R Ab) was positive with high titre. A kidney biopsy was performed showing a double nephropathy: a focal segmental glomerulosclerosis (FSGS) with some collapsing features, superimposed on membranous glomerulonephritis (Fig. 1). RESULTS: We started the Ponticelli regimen (alternate months steroids and cyclophosphamide). After the first month of therapy, blood tests revealed creatinine 1.7 mg/dL, haemoglobin 11.7 g/dL;serum albumin 2.7 g/dL and urinalysis without microscopic haematuria. At the third month of therapy, the patient developed atrial fibrillation and started anticoagulation;blood tests were as follows: creatinine 1.1 mg/dL, serum albumin 3.0 g/dL, Ab anti-MPO 7 UA/mL and PLA2R Ab was absent. A left ocular, frontal and parietal herpes zoster induced a short discontinuation of therapy and responded well to Acyclovir;then we concluded the fourth month of therapy. At the fifth month, a SARS CoV 2 RT PCR unexpectedly resulted positive;the patient remained asymptomatic, but we stopped definitively the therapy. One month later, blood tests showed: creatinine 1 mg/dL, serum albumin 4 g/dL, proteinuria 0.7 g/die, MPO 2 UA/mL and PLA2R Ab absent. CONCLUSION: To our knowledge, this is the first case of nephrotic sindrome secondary to a De novo MN and FSGS, associated with positive MPO antibody, following Pfizer-BioNTech mRNA vaccination COVID 19;the patient responded well to immunosoppression going in remission and regaining renal function. (Figure Presented).