Herpetic Keratitis Research Articles

Bilateral Herpes Simplex Keratoconjungtivitis: A Case Report

Introduction: Herpes Simplex Virus (HSV) is one of the DNA viruses known to infect the human eye. Herpes simplex keratitis is, in general, a unilateral disease. Simultaneous bilateral involvement is a rare occurrence that has been observed in patients with compromised immune systems. Purpose: To report a case of bilateral herpes simplex keratoconjunctivitis Case Report: A 22-year-old man arrives with the primary complaint of redness in both eyes in the last four days. The patient complained of blurred vision, tearing, and foreign body sensations. Ophthalmology examination of both eyes revealed visual acuity of 1.0 in the right eye and 0.8 in the left eye, a dendritic lesion, and a decrease in corneal sensation. Patient was diagnosed with bilateral keratoconjunctivitis HSV and was treated with acyclovir ointment, levofloxacin eye drops, acyclovir 400 mg five times a day, and vitamin C 500 mg. Discussion: Bilateral herpes simplex keratitis can occur in both immunocompromised and immunocompetent individuals. Recurrence of HSV infectious keratitis is common. Factors such as emotional stress, fever, postoperative tear dysfunction, ultraviolet (UV-A) radiation exposure, and ocular (accidental or surgical) trauma have also been related to the reactivation of the herpes simplex virus. History, physical, and laboratory examinations support the patient?s diagnosis in order to get the appropriate treatment. Conclusion: Simultaneously occurring bilateral herpetic keratitis has a high proportion of complications, either because of the greater virulence of the virus or because of altered host susceptibility. Therefore, prompt administration of medication upon diagnosis is essential to reduce the severity and frequency of viral attacks and delay the progression of corneal damage.

Formulation and Evaluation of Ophthalmic Novel In-Situ Gel Containing Acyclovir for the Treatment of Herpes Simplex Keratitis

Herpes Simplex Keratitis (HSK), which is a major reason of corneal infection. The virus (Herpes simplex virus) enters into a latent phase. It presents primary infection as conjunctiva and eyelids swelling and mild inflammation. According to global research of disease, it is around 1.4 million, including 38,000 new cases of visual impairment or blindness every year. Several oral and topical antiviral drugs for HSK are out there commercially. However, toxicity and low patient compliance hamper use in HSK. Thus, an effective and safe delivery for HSK is required. The conventional ocular delivery systems such as suspension, solutions and ointments show drawbacks like increased low efficiency, pre-corneal elimination and blurred vision respectively, resulting to poor bioavailability. Ophthalmic In-situ gels, which are viscous polymer-based liquids are instilled in eyes as drops that undergoes sol-to-gel transition that improve duration of corneal contact and ocular bioavailability and thereby reducing frequency of administration. Merits of Ophthalmic in-situ gels over conventional dosage forms are possibility of releasing drugs at constant and slow rate with increased ocular residence time, increased shelf life and accurate dosing. This research includes ion induced in-situ-forming polymeric systems using combination of gelling agents to prolong corneal contact time, eradicate drug elimination and increase the bioavailability.

Ophthalmic Solutions with a Broad Antiviral Action: Evaluation of Their Potential against Ocular Herpetic Infections.

HSV-1 can be associated with severe and recurrent eye infections characterized by a strong inflammatory response that leads to blepharoconjunctivitis, epithelial and stromal keratitis, and retinal necrosis. The incidence of HSV-1 keratitis is 1.5 million every year worldwide, including more than 40,000 new cases exhibiting serious visual failures. Generally, the therapy uses antiviral drugs to promote healing; however, there are currently no compounds that are able to completely eradicate the virus. In addition, the phenomenon of resistance is rapidly spreading among HSV-1 strains, creating mutants developing resistance to the common antiviral drugs; therefore, deep research on this issue is warranted. The efficacy of different ophthalmic solutions already on the market was evaluated for reducing HSV-1 infection. Different plaque assays were set up on epithelial cells, revealing that two ophthalmic solutions were able to inhibit viral replication in the early stages of infection. The data were further confirmed by molecular tests analyzing the expression levels of the principal genes involved in HSV-1 infection, and a strong reduction was observed after only 1 min of eye-drop treatment. Collectively, these results suggested the use of ophthalmic solutions as potential antiviral options for the treatment of ocular herpetic infection.

Метод лечения рецидивирующего герпетического кератита на основе послойной кератопластики с фемтосекундным сопровождением (серия клинических случаев)

Purpose. To evaluate the clinical efficacy of lamellar keratoplasty in the treatment of recurrent herpetic keratitis with femtosecond laser-assisted corneal surgery. Material and methods. In two clinical cases, lamellar keratoplasty with femtosecond laser-assisted corneal surgery was performed. Preoperative and postoperative visual acuity, refractometry, keratotopography, pachymetry were examined. Conducted courses of conservative treatment: antiviral, anti-inflammatory, desensitization therapy using vaccination «Vitogerpavak». Results. Evidence of the effectiveness of the proposed method was obtained - stabilization and relief of the inflammatory process, increased visual acuity and cosmetic effect. Conclusion. Cases of successful treatment of recurrent herpetic keratitis after intensive courses of conservative treatment followed by lamellar keratoplasty with femtosecond laser-assisted surgery are presented. The use of femtolaser technologies, which allow dosed excision of the affected tissue at a certain depth according to predetermined parameters, contributes to the achievement of high functional results. Lamellar keratoplasty with the maximum possible excision of scar tissue and its replacement with a donor cornea is a minimally invasive effective method to restore the transparency of the cornea after therapeutic treatment of recurrent herpetic keratitis. Key words: keratoplasty, herpetic keratitis, femtosecond laser

E3 ligase RNF5 inhibits type I interferon response in herpes simplex virus keratitis through the STING/IRF3 signaling pathway.

Herpes simplex keratitis (HSK), caused by the herpes simplex virus 1 (HSV-1), is a major blinding disease in developed countries. HSV-1 can remain latent in the host for life and cannot be eradicated. The infection causes the secretion of various cytokines and aggregation of inflammatory cells. In the early stage of inflammation, mainly neutrophils infiltrate the cornea, and CD4+ T cells mediate the immunopathological changes in herpetic stromal keratitis in the subsequent progression. The STING/IRF3-mediated type I interferon (IFN) response can effectively inhibit viral replication and control infection, but the activity of STING is affected by various ubiquitination modifications. In this study, we found that the expression of RNF5 was elevated in corneal tissues and corneal epithelial cells after infection with HSV-1. Immunofluorescence staining confirmed that RNF5 was mainly expressed in the corneal epithelial layer. We silenced and overexpressed RNF5 expression in corneal epithelial cells and then inoculated them with HSV-1. We found that the expressions of STING, p-IRF3, p-TBK1, and IFN-β mRNA increased after RNF5 silencing. The opposite results were obtained after RNF5 overexpression. We also used siRNA to silence RNF5 in the mouse cornea and then established the HSK model. Compared with the siRNA-control group, the siRNA-RNF5 group showed significantly improved corneal inflammation, reduced clinical scores and tear virus titers, and significantly increased corneal IFN-β expression. In addition, the expressions of the proinflammatory cytokines IL-6 and TNF-α in the corneal tissue were significantly decreased, indicating that RNF5 silencing could effectively promote IFN-I expression, inhibit virus replication, alleviate inflammation, and reduce corneal inflammatory damage. In summary, our results suggest that RNF5 limits the type I IFN antiviral response in HSV corneal epithelitis by inhibiting STING/IRF3 signaling.

Evaluating the therapeutic efficacy of triptolide and (S)-10-hydroxycamptothecin on cutaneous and ocular Herpes Simplex Virus type-1 infections in mice

ObjectiveThe emergence of Acyclovir-Resistant Herpes Simplex Virus type-1, which is the result of clinical over usage calls for the urgent need of a novel anti-HSV agent. Hence, the activity of Triptolide (TP) and (S)-10-Hydroxycamptothecin (10-HCPT) were investigated as natural products in two infection models of HSV-1. MethodsThe antiviral efficacy of TP and 10-HCPT was evaluated in mice ocular and cutaneous infection models of HSV. Groups of 10 mice were infected with HSV-1. Both compounds were administered topically on corneal and skin. The disease severity, viral titer (plaque reduction assay), and histopathology were evaluated in the ocular and cutaneous models of HSV-1 infection on days 3, 5, 7, 9, and 12 post infection, as well as genome loads on days 3 and 12. ResultsTopical treatment of corneal with TP, 10-HCPT, and ACV was effective in reducing stromal disease (after day 3, P = 0.001), plus TP and ACV on vascularization (after day 7, P = 0.001). The virus titer decreased significantly in the infected treated groups after day 3 (P < 0.05). Also, on day 12 post-infection, the virus genome volume in the TP and ACV groups was significantly reduced. With respect to virus titers and the DNA yield, significant difference was observed, merely in the ACV group in comparison to the control (P = 0.013). Immunohistochemistry analysis showed that corneal epithelium healing was partially visible in the 10-HCPT group, which gradually increased in TP, and was the highest in the ACV group. The skin epithelium healing was only observed in TP and ACV groups, and was superior in the ACV group. ConclusionsThis study revealed the virologic and clinical potential of TP in-vivo to treat ocular mouse model.

Herpetic Eye Disease Following the SARS-CoV-2 Vaccinations

ABSTRACT Purpose To describe herpetic ocular infections following SARS-CoV-2 vaccinations. Methods A retrospective study of herpetic ocular infections after BNT162b2mRNA vaccination and a literature review. Results A cohort of five patients: three varicella zoster virus (VZV) and two herpes simplex virus (HSV) cases, as well as 19 literature cases: 9 cases of VZV and 10 cases of HSV post BNT162b2mRNA, AZD1222, mRNA-1273, and CoronaVac vaccinations. All cases presented within 28 days post vaccination. Most VZV and HSV cases (15/19) reported in the literature presented post first vaccine dose, while in our cohort 2 VZV cases presented post second dose and both HSV cases and one VZV case post third dose. The most common presentations were HZO with ocular involvement and HSV keratitis. All eyes had complete resolution; however, one had retinal detachment and three corneal scars. Conclusion Herpetic ocular infections may develop shortly after SARS-CoV-2 vaccinations. Overall, the outcome is good.

Hypopyon after Periocular Corticosteroid Injection: A Case Series

ABSTRACT Purpose The purpose of this study was to describe a case series of hypopyon after periorbital corticosteroid injection. Methods This was a retrospective, observational case series investigating hypopyon cases after injection of periorbital steroid patients. Results We presented three patients manifested hypopyon after periocular corticosteroid injection. All three cases were diagnosed as HSV stromal keratitis or endotheliitis and treated successfully with topical steroids as well as systemic and topical antiviral treatment. Conclusion HSV keratitis is not recommend when treated with periocular corticosteroid injection. Topical corticosteroid is the best choice for HSV stromal keratitis and HSV endotheliitis.

Recent approaches to combat various infections in eye

The prevalence of various eye related disorder is increasing rapidly among the global population and the microorganism borne ocular infections are emerging as biggest threat to the healthy functioning of eye during the past few years. Conjunctivitis, keratitis, endophthalmitis, blepharitis, uveitis, cellulitis, and ocular herpes are a few of the more common ocular illnesses. The arrival of novel technologies including nanotechnology and ocular implant are giving a hope to the healthcare sector via improved therapeutic potential and safety profile in the field of ocular infections treatment. This article enlisted major ocular infections, along with the physiology, prevention and treatment methods. The review article also highlighted information related to the available treatments for various ocular infections and recent patent insight of emerging technologies.

Swarms of chemically modified antiviral siRNA targeting herpes simplex virus infection in human corneal epithelial cells.

Herpes simplex virus type 1 (HSV-1) is a common virus of mankind and HSV-1 infections are a significant cause of blindness. The current antiviral treatment of herpes infection relies on acyclovir and related compounds. However, acyclovir resistance emerges especially in the long term prophylactic treatment that is required for prevention of recurrent herpes keratitis. Earlier we have established antiviral siRNA swarms, targeting sequences of essential genes of HSV, as effective means of silencing the replication of HSV in vitro or in vivo. In this study, we show the antiviral efficacy of 2´-fluoro modified antiviral siRNA swarms against HSV-1 in human corneal epithelial cells (HCE). We studied HCE for innate immunity responses to HSV-1, to immunostimulatory cytotoxic double stranded RNA, and to the antiviral siRNA swarms, with or without a viral challenge. The panel of studied innate responses included interferon beta, lambda 1, interferon stimulated gene 54, human myxovirus resistance protein A, human myxovirus resistance protein B, toll-like receptor 3 and interferon kappa. Our results demonstrated that HCE cells are a suitable model to study antiviral RNAi efficacy and safety in vitro. In HCE cells, the antiviral siRNA swarms targeting the HSV UL29 gene and harboring 2´-fluoro modifications, were well tolerated, induced only modest innate immunity responses, and were highly antiviral with more than 99% inhibition of viral release. The antiviral effect of the 2’-fluoro modified swarm was more apparent than that of the unmodified antiviral siRNA swarm. Our results encourage further research in vitro and in vivo on antiviral siRNA swarm therapy of corneal HSV infection, especially with modified siRNA swarms.

CD137 costimulation is associated with reduced herpetic stromal keratitis and with developing normal CD8+ T cells in trigeminal ganglia.

Costimulatory interactions can be critical in developing immune responses to infectious agents. We recently reported that herpes simplex type 1 (HSV-1) infections of the cornea require a functional CD28-CD80/86 interaction to not only reduce the likelihood of encephalitis, but also to mediate herpetic stromal keratitis (HSK) following viral reactivation. In this same spirit we decided to determine the role that CD137 costimulation plays during HSK. Using both B6-CD137L-/- mice, as well as antagonistic and agonistic antibodies to CD137 we characterize the immune response and to what extent CD137 plays an important role during this disease. Immune responses were measured in both the cornea and in the trigeminal ganglia where the virus forms a latent infection. We demonstrate that CD137 costimulation leads to reduced corneal disease. Interestingly, we observed that lack of CD137 costimulation resulted in significantly reduced CD8+ T expansion and function in the trigeminal ganglia. Finally, we showed that viruses that have been genetically altered to express CD137 display significantly reduced corneal disease, though they did present similar levels of trigeminal infection and peripheral virus production following reactivation of a latent infection. CD137 interactions lead to reduced HSK and are necessary to develop robust trigeminal CD8+ T cell responses.

Bioengineering corneal transplantation for treatment of herpes simplex keratitis complicated corneal leukoplakia

<p indent="0mm">Bioengineering cornea used for lamellar keratoplasty holds significant efficacy, high safety and good prognosis in the treatment of severe corneal disorders, which may be used as a substitute when donor cornea is deficient. The most important characteristics to be considered for bioengineering cornea are suitable mechanical properties, biocompatibility, and transparency, which have been shown to mimic the human corneal extracellular matrix and enhance cell differentiation. Currently, the bioengineering corneal transplantation is the most common tissue equivalent in the treatment of infectious corneal ulcer. We reports here a case of bioengineering corneal transplantation for herpes simplex keratitis (HSK) complicated corneal leukoplakia.

Neurotrophic Keratopathy in the United States: An Intelligent Research in Sight Registry Analysis

To describe the characteristics of neurotrophic keratopathy (NK) in the United States. Retrospective database study. Thirty-one thousand nine hundred fifteen eyes of 27 483 patients with a diagnosis of NK. Retrospective analysis of visits associated with a diagnosis of NK between 2013 and 2018 using the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry. Demographic information, prevalence, visual acuity (VA), concomitant diagnosis and procedure codes, and risk factors impacting VA most closely after NK onset date. Mean ± standard deviation (SD) age at initial diagnosis of NK was 68.0 ± 16.0 years, and 58.91% of patients were women (P &lt; 0.0001). Presentation was unilateral in 58.14%, bilateral in 16.13%, and unspecified in 25.73%. Average 6-year prevalence of NK in the IRIS Registry was 21.34 cases per 100 000 patients. Mean ± SD VA was 0.60 ± 0.79 logMAR before diagnosis and 0.88 ± 0.94 logMAR after diagnosis (P &lt; 0.0001). Most common concomitant diagnoses included herpetic keratitis (33.70%), diabetes (31.59%), and corneal dystrophy (14.28%). Common procedures for NK management included the use of amniotic membrane (29.90%), punctal plugs (29.65%), and bandage contact lenses (22.67%). Age, male sex, Black race, Hispanic or Latino ethnicity, unilateral involvement, concomitant diagnoses of diabetes, corneal transplantation, and herpetic keratitis were associated significantly with worse VA. Based on the IRIS Registry, the prevalence of NK is 21.34 cases per 100 000 patients. Visual acuity was significantly worse after NK diagnosis compared with other time points. Neurotrophic keratopathy was associated most commonly with herpetic keratitis and diabetes. Worse VA in patients with NK was associated with several demographic characteristics, history of diabetes, corneal transplantation, and herpetic keratitis.

Incidence and Risk Factors of Bilateral Herpetic Keratitis: 2022 Update.

Simultaneously occurring bilateral herpetic keratitis is a rare clinical manifestation of ocular herpes. Immunocompromised patients are more susceptible to develop bilateral disease. The purpose of this study is to review recent literature on the topic and to highlight latest updates, regarding risk factors and possible correlations to the disease, as well as new therapeutic options.

Infectious keratitis: A review.

Globally, infectious keratitis is the fifth leading cause of blindness. The main predisposing factors include contact lens wear, ocular injury and ocular surface disease. Staphylococcus species, Pseudomonas aeruginosa, Fusarium species, Candida species and Acanthamoeba species are the most common causal organisms. Culture of corneal scrapes is the preferred initial test to identify the culprit organism. Polymerase chain reaction (PCR) tests and in vivo confocal microscopy can complement the diagnosis. Empiric therapy is typically commenced with fluoroquinolones, or fortified antibiotics for bacterial keratitis; topical natamycin for fungal keratitis; and polyhexamethylene biguanide or chlorhexidine for acanthamoeba keratitis. Herpes simplex keratitis is mainly diagnosed clinically; however, PCR can also be used to confirm the initial diagnosis and in atypical cases. Antivirals and topical corticosteroids are indicated depending on the corneal layer infected. Vision impairment, blindness and even loss of the eye can occur with a delay in diagnosis and inappropriate antimicrobial therapy.

Commentary: Corneal neurotization

Commentary: Corneal neurotization

Prevalence and characteristics of ocular diseases in Sphynx cats: A retrospective assessment (2012-2021) and comparison with non-Sphynx cats.

To describe the prevalence of ocular diseases in Sphynx cats, and compare disease characteristics with other feline breeds. Medical records of Sphynx cats presented to an ophthalmology referral center between 1/2012 and 4/2021 were examined. Cats of other breeds examined during the same period served as controls. One hundred ten Sphynx cats were examined during the study period, diagnosed with corneal sequestrum (n= 42 cats), lower eyelid entropion (n= 25), presumed herpetic keratoconjunctivitis (n= 19), conjunctivitis (n= 7), corneal ulcers (n= 6), nasolacrimal duct atresia/obstruction (n= 6), corneal dystrophy (n= 3), eosinophilic keratitis (n= 2), uveitis (n= 2), non-ulcerative keratitis (n= 1), and cataract (n= 1). Corneal sequestrum was significantly more common in Sphynx versus non-Sphynx cats (odds ratio=8.0, 95% CI=5.3-12.2, p< .001), and age of diagnosis was significantly younger in Sphynx cats (2.0± 1.5 years vs. 5.9± 4.0 years, p< .001). Corneal sequestrum recurrence was noted in 19.4% Sphynx eyes and 6.4% non-Sphynx eyes undergoing surgery (p= .015). Lower eyelid entropion-most often bilateral (80%)-was significantly more common in Sphynx versus non-Sphynx cats (odds ratio=4.1, 95% CI=2.3-7.1, p< .001), and age of diagnosis was significantly younger in Sphynx cats (0.9± 1.4 years vs. 3.5± 3.3 years, p< .005). Corneal sequestrum and entropion were overrepresented and diagnosed at an earlier age in Sphynx cats when compared with the general feline population. Given the high prevalence, early age of onset, and relatively high recurrence of corneal sequestrum in Sphynx cats, further studies are warranted to better understand etiopathogenesis and preferred therapies.

Analyse vectorielle de la correction de l’astigmatisme par incisions arciformes au laser femtoseconde dans les astigmatismes géants post-kératoplastie transfixiante

To study the results of femtosecond laser-assisted arcuate keratotomy in extreme astigmatism after penetrating keratoplasty, using a Ziemer LDVZ6 with a modified Lindstrom nomogram. Case series, retrospective study. Consecutive eyes that underwent femtosecond laser-assisted arcuate keratotomy between 2014 and 2019 in the Nantes University Hospital for extreme astigmatism after penetrating keratoplasty were included. Twenty-four eyes of 24 patients were included. The mean age was 53.3±12.2 years at the time of the arcuate keratotomies. Indications for penetrating keratoplasty were keratoconus in 66.7% of cases, herpes keratitis in 16.7% of cases, and corneal dystrophy in 16.7% of cases. The mean initial best corrected visual acuity was 0.36±0.23 logMar versus 0.26±0.15 logMar at the 3-month postoperative visit (P=0.04). At the postoperative visit, 54% (13/24) of eyes had improved best corrected visual acuity (BCVA), and 25% had no change in BCVA, with a mean cylinder reduction of 3.3 diopters. The mean preoperative topographic cylinder was 9.5±3.2 diopters versus 6.2±2.8 diopters postoperatively (absolute values; P<0.001), i.e. a 34.7% reduction in astigmatism. At the 3-month postoperative visit, 20.8% of eyes (5/24) had topographic astigmatism less than 3 diopters with a mean astigmatism reduction of 97±55% (range: 17; 201) using the Alpins method. No suppurative keratitis or endophthalmitis were observed. Twenty-one percent of patients underwent a second arcuate keratotomy after 3 to 6 months due to insufficient refractive results. Development of new nomograms designed for extreme astigmatism after penetrating keratoplasty would enhance the precision and reproducibility of femtosecond laser-assisted arcuate keratotomy in these cases.

Initial TK-deficient HSV-1 infection in the lip alters contralateral lip challenge immune dynamics

Primary infection with herpes simplex type 1 (HSV-1) occurring around the mouth and nose switches rapidly to lifelong latent infection in sensitive trigeminal ganglia (TG) neurons. Sporadic reactivation of these latent reservoirs later in life is the cause of acute infections of the corneal epithelium, which can cause potentially blinding herpes simplex keratitis (HSK). There is no effective vaccine to protect against HSK, and antiviral drugs provide only partial protection against recurrences. We previously engendered an acute disease-free, non-reactivating latent state in mice when challenged with virulent HSV-1 in orofacial mucosa, by priming with non-neurovirulent HSV-1 (TKdel) before the challenge. Herein, we define the local immune infiltration and inflammatory chemokine production changes after virulent HSV-1 challenge, which were elicited by TKdel prime. Heightened immunosurveillance before virulent challenge, and early enhanced lymphocyte-enriched infiltration of the challenged lip were induced, which corresponded to attenuation of inflammation in the TG and enhanced viral control. Furthermore, classical latent-phase T cell persistence around latent HSV-1 reservoirs were severely reduced. These findings identify the immune processes that are likely to be responsible for establishing non-reactivating latent HSV-1 reservoirs. Stopping reactivation is essential for development of efficient vaccine strategies against HSV-1.

MO230: 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

Abstract 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. Anti-phosholipase 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.