Persistent COVID-19 in immunocompromised patients-Israeli society of infectious diseases consensus statement on diagnosis and management.

BACKGROUND: Immunocompromised patients with impaired humoral immunity are at risk for persistent COVID-19 (pCOVID), a protracted symptomatic disease with active viral replication. OBJECTIVES: To establish a national consensus statement on the diagnosis, treatment, management, isolation, and prevention of pCOVID in adults. SOURCES: We base our suggestions on the available literature, our own experience, and clinical reasoning. CONTENT: Literature on the treatment of pCOVID is scarce and consists of few case reports and case series. The available studies provide low-quality evidence for monoclonal antibodies, convalescent plasma, antiviral drugs, and immunomodulators. Different combination therapies are described. Continuous viral replication and antiviral treatment may lead to the development of mutations that confer resistance to therapy. IMPLICATIONS: To reduce the risk of resistance and improve outcomes, we suggest treating pCOVID with a combination of antibody-based therapy and two antiviral drugs for duration of 5-10 days. Immunomodulatory therapy can be added in patients with an inflammatory clinical picture. In cases of treatment failure or relapse, prolonged antiviral treatment can be considered. For the prevention of pCOVID, we suggest active and passive vaccination and early initiation of treatment for acute COVID-19. Additional research on pCOVID treatment is urgently needed.

Dual anti-viral treatment for persistent COVID-19 in immunocompromised hemato-oncological patients is associated with a favorable prognosis and minor side effects.

In hemato-oncological patients, COVID-19 can present as a persistent infection with ongoing symptoms and viral replication over a prolonged period of time. Data are scarce on the preferred treatment options for these patients. We describe our experience with a five-day course of dual anti-viral treatment with remdesivir and nirmatrelvir/ritonavir for hemato-oncological immunocompromised patients with persistent COVID-19. Fifteen patients with a history of lymphoma, CLL, and MM were included. Eight were male, median age was 74. All patients had an immediate clinical and virological response. In 73 % of patients, PCR for SARS-CoV-2 became negative at the end of treatment and the rest had an increase in PCR cycle threshold (CT) values, with a median increase of 6 cycles. After a follow-up of three months, 60 % of patients remained in full clinical and virological remission. None required invasive mechanical ventilation or died. The side effects we observed, neutropenia, lactatemia and elevated transaminases, were mild and almost all transient in nature. We conclude that dual anti-viral treatment appears to be a valid treatment option for persistent COVID-19.

The clinical significance of Dientamoeba fragilis and Blastocystis in human stool-retrospective cohort study.

OBJECTIVES: The aim of this study was to assess the clinical significance of Dientamoeba fragilis (DF) and Blastocystis species (Bs) in human stool. METHODS: Observational study of patients ≥18 years, who were tested by stool multiplex PCR for bacteria and parasites between April 2019 and March 2022. Although DF and Bs are part of the PCR kit, these results are not routinely reported to the patient or the ordering physician. The main outcomes were the incidence of symptoms during 14 days before the referral to stool PCR test, and the incidence of several clinical outcomes during 60 days after the PCR test (symptoms, referrals to further evaluation, prescription of symptomatic, or antibiotic treatment). RESULTS: A total of 27 918 patients were tested by stool PCR during the 3 study years. A total of 6215 (22.3%) and 5337 (19.2%) were positive for DF and Bs, respectively. The incidence of symptoms before the test was similar in those positive for Bs or DF and those with all-negative PCR (adjusted OR and 95% CI of 0.87 [0.80-0.95] and 0.82 [0.76-0.88] for Bs and DF, respectively), whereas significantly higher (2.47 [2.23-2.73]) in those positive for the other multiplex PCR assay components. During the 60 days after the test, the prevalence of any of the outcomes was similar in those positive for Bs or DF and those with negative PCR (adjusted OR and 95% CI of 0.92 [0.83-1.02] and 0.89 [0.81-0.97] for symptoms, 0.84 [0.75-0.94] and 0.93 [0.85-1.01] for referrals, 0.88 [0.75-1.03] and 0.82 [0.71-0.94] for symptomatic treatment, and 0.88 [0.75-1.02] and 0.86 [0.75-0.98] for antibiotic treatment in the Bs and DF positive individuals, respectively). The PCR cycle threshold was not associated with any of the outcomes. DISCUSSION: Positive stool PCR for DF or Bs was not associated with any of the measured clinical outcomes.

Emergence of artemisinin-based combination treatment failure in patients returning from sub-Saharan Africa with P. falciparum malaria.

BACKGROUND: Artemisinin-based combination therapies (ACTs) are recommended as first-line treatment against uncomplicated Plasmodium falciparum infection. Mutations in the PfKelch13 (PF3D7_1343700) gene led to resistance to artemisinin in Southeast Asia. Mutations in the Pfcoronin (PF3D7_1251200) gene confer reduced artemisinin susceptibility in vitro to an African Plasmodium strain, but their role in clinical resistance has not been established. METHODS: We conducted a retrospective observational study of Israeli travellers returning from sub-Saharan Africa with P. falciparum malaria, including patients with artemether-lumefantrine (AL) failure. Blood samples from all malaria-positive patients are delivered to the national Parasitology Reference Laboratory along with personal information. Confirmation of malaria, species identification and comparative parasite load analysis were performed using real-time PCR. DNA extractions from stored leftover samples were analysed for the presence of mutations in Pfkelch13 and Pfcoronin. Age, weight, initial parasitaemia level and Pfcoronin status were compared in patients who failed treatment vs responders. RESULTS: During 2009-2020, 338 patients had P. falciparum malaria acquired in Africa. Of those, 15 (24-69 years old, 14 males) failed treatment with AL. Four were still parasitemic at the end of treatment, and 11 had malaria recrudescence. Treatment failure rates were 0% during 2009-2012, 9.1% during 2013-2016 and 17.4% during 2017-2020. In all patients, the Pfkelch13 propeller domain had a wild-type sequence. We did find the P76S mutation in the propeller domain of Pfcoronin in 4/15 (28.6%) of the treatment-failure cases compared to only 3/56 (5.5%) in the successfully treated patients (P = 0.027). CONCLUSION: AL treatment failure emergence was not associated with mutations in Pfkelch13. However, P76S mutation in the Pfcoronin gene was more frequently present in the treatment-failure group and merits further investigation. The increase of malaria incidence in sub-Saharan-Africa partly attributed to the COVID-19 pandemic might also reflect a wider spread of ACT resistance.

New Insights on DR and DQ Human Leukocyte Antigens in Anti-LGI1 Encephalitis.

BACKGROUND AND OBJECTIVES: To explore the clinical characteristics and HLA associations of patients with anti-leucine-rich glioma-inactivated 1 encephalitis (LGI1E) from a large single center in Israel. Anti-LGI1E is the most commonly diagnosed antibody-associated encephalitic syndrome in adults. Recent studies of various populations reveal significant associations with specific HLA genes. We examined the clinical characteristics and HLA associations of a cohort of Israeli patients. METHODS: Seventeen consecutive patients with anti-LGI1E diagnosed at Tel Aviv Medical Center between the years 2011 and 2018 were included. HLA typing was performed using next-generation sequencing at the tissue typing laboratory of Sheba Medical Center and compared with data from the Ezer Mizion Bone Marrow Donor Registry, containing over 1,000,000 samples. RESULTS: Our cohort displayed a male predominance and median age at onset in the 7th decade, as previously reported. The most common presenting symptom was seizures. Notably, paroxysmal dizziness spells were significantly more common than previously reported (35%), whereas faciobrachial dystonic seizures were found only in 23%. HLA analysis revealed overrepresentation of DRB1*07:01 (OR: 3.18, CI: 20.9 p < 1.e-5) and DRB1*04:02 (OR: 3.8, CI: 20.1 p < 1.e-5), as well as of the DQ allele DQB1*02:02 (OR: 2.8, CI: 14.2 p < 0.0001) as previously reported. A novel overrepresentation observed among our patients was of the DQB1*03:02 allele (OR: 2.3, CI: 6.9 p < 0.008). In addition, we found DR-DQ associations, among patients with anti-LGI1E, that showed complete or near-complete linkage disequilibrium (LD). By applying LD analysis to an unprecedentedly large control cohort, we were able to show that although in the general population, DQB*03:02 is not fully associated with DRB1*04:02, in the patient population, both alleles are always coupled, suggesting the DRB1*04:02 association to be primary to disease predisposition. In silico predictions performed for the overrepresented DQ alleles reveal them to be strong binders of LGI1-derived peptides, similarly to overrepresented DR alleles. These predictions suggest a possible correlation between peptide binding sites of paired DR-DQ alleles. DISCUSSION: Our cohort presents distinct immune characteristics with substantially higher overrepresentation of DRB1*04:02 and slightly lower overrepresentation of DQB1*07:01 compared with previous reports implying differences between different populations. DQ-DR interactions found in our cohort may shed additional light on the complex role of immunogenetics in the pathogenesis of anti-LGI1E, implying a possible relevance of certain DQ alleles and DR-DQ interactions.

An outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infections among hospital personnel with high mRNA vaccine uptake.

Real-world studies have demonstrated impressive effectiveness of the BNT162b2 COVID-19 vaccine in preventing symptomatic and asymptomatic SARS-CoV-2 infection. We describe an outbreak of SARS-CoV-2 infections in a hospital with high vaccine uptake. We found a low secondary attack rate (7%), suggesting low infectivity of vaccinated persons with vaccine breakthrough SARS-CoV-2 infections.

Mpox Presenting as Proctitis in Men Who Have Sex With Men.

In our cohort of 70 patients of men who have sex with men (MSM) with mpox, more than one-third presented with proctitis. In two-thirds of proctitis patients, there was no typical rash upon presentation, and in one-fifth, there was no rash at all, making the diagnosis a challenge. A rectal swab for mpox polymerase chain reaction (PCR) can be diagnostic.

Bilateral hearing loss preceding rhomboencephalitis - a hint for Kelch-like 11 syndrome.

BACKGROUND: Paraneoplastic neurological syndromes have diverse clinical presentations and offer an opportunity for early diagnosis of malignancy and treatment. Recently, a new paraneoplastic syndrome associated with seminoma was described, consisting of rhombencephalitis with antibodies targeting the Kelch-like protein 11 (KLHL11). Questions were raised as to the spectrum of clinical symptoms and strength of association to seminoma. METHODS: We present a 45-year-old man with bilateral sensorineural hearing loss, vertigo, and progressive ataxia. An extensive diagnostic workup led to the diagnosis of anti-KLHL11 paraneoplastic syndrome based on an immunofluorescence assay showing a typical pattern and a confirmatory serological assay. As a result, the patient underwent a meticulous search for an underlying seminoma. RESULTS: Although initially, all images were interpreted as negative, a revision of the positron emission tomography-CT (PET-CT) examination identified a small mediastinal suspicious mass. The mass was resected, and pathological examination confirmed it to be an extra-testicular seminoma. CONCLUSIONS: Patients presenting with progressive sensorineural hearing loss, vertigo, and ataxia should be evaluated for KLHL11 paraneoplastic syndrome. Furthermore, we support a strong association between anti-KLH11 rhombencephalitis and an underlying seminoma and recommend a thorough search for an undiagnosed germ cell tumor in these patients.

Drivers of adaptive evolution during chronic SARS-CoV-2 infections.

In some immunocompromised patients with chronic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, considerable adaptive evolution occurs. Some substitutions found in chronic infections are lineage-defining mutations in variants of concern (VOCs), which has led to the hypothesis that VOCs emerged from chronic infections. In this study, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of 27 chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations; however, a subset of mutations associated with successful global transmission was absent from chronic infections. We further tested the ability to associate antibody evasion mutations with patient-specific and virus-specific features and found that viral rebound is strongly correlated with the emergence of antibody evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody evasion in particular niches in a patient's body. We suggest that a tradeoff exists between antibody evasion and transmissibility and that extensive monitoring of chronic infections is necessary to further understanding of VOC emergence.

Acute Kidney Injury Recovery Patterns in ST-Segment Elevation Myocardial Infarction Patients.

Background: Acute kidney injury (AKI) is a frequent complication in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Identification of different AKI recovery patterns may improve patient prognostic stratification. We investigated the clinical relevance of AKI recovery patterns among STEMI patients undergoing PCI. Methods: A retrospective study of 2943 STEMI patients undergoing PCI. The incidence of renal impairment, in-hospital complications, short and long-term mortality, were compared between patients without AKI, with early recovery defined as a return to baseline creatinine within 72 h, and no AKI recovery/delayed recovery defined as all other AKI cases. Results: A total of 255 (8.7%) patients developed AKI, of whom 124/255 (49%) patients had an early recovery, whereas 131/255 (51%) had no AKI recovery/delayed recovery. Patients without recovery were more likely to have in-hospital complications and higher long-term mortality (36.64% vs. 7.25%%; p < 0.001). In a multivariable regression model, the mortality hazard ratio (HR) for long term mortality remained significant for patients with no/delayed recovery AKI (HR 7.76, 95% CI 4.69 to 12.86, p < 0.001), and a strong trend among patients with resolving AKI (HR 2.09, 95% CI 0.933−4.687, p = 0.071). Conclusions: Among STEMI patients undergoing PCI, the recovery pattern of AKI is a valuable prognostic marker.

Clinical features and outcomes of bacteremic and non-bacteremic Campylobacteriosis: a case-control study.

PURPOSE: Campylobacter bloodstream infection (C-BSI) is uncommon, and its clinical significance is unclear. The aim of the study was to determine risk factors and clinical outcomes associated with Campylobacter BSI. METHODS: We performed a single center retrospective case-control study comparing patients with C-BSI (cases) and patients with nonbacteremic Campylobacter enteritis (controls), from January 2007 through June 2020. Case and control patients were matched by age and sex at a ratio of 1:2. Demographic, clinical, and microbiological characteristics were compared between groups. RESULTS: We identified 76 patients with C-BSI and matched them with 149 nonbacteremic patients with Campylobacter enteritis. Rates of C-BSI increased tenfold in 2014 following the introduction of BacTAlert FA/FN Plus blood culture bottles. Baseline variables significantly associated with C-BSI on multivariable logistic regression were fever, absence of diarrhea and recent exposure to antibiotics. Compared with controls, C-BSI was associated with higher 30-day mortality (12% vs. 2%, P = 0.003), more frequent need for intensive care (6.6% vs. 1.2%, P = 0.032) and longer hospital stay (median, 5 days vs. 3 days, P = 0.003). There was a high proportion of immunocompromised patients in both groups (55%). CONCLUSIONS: C-BSI is identified with increasing frequency, reflecting both changes in epidemiology and improved sensitivity of blood culture systems. Our findings indicate that detection of Campylobacter spp. in blood culture is associated with significantly higher rates of death and other adverse outcomes.

Short-Term Safety of Booster Immunization With BNT162b2 mRNA COVID-19 Vaccine in Healthcare Workers.

This study demonstrated a favorable short-term safety profile after a third dose of the BNT162b2 vaccine among healthcare workers (HCWs). There were more frequent local reactions and less systemic reactions compared to the second dose. The HCWs who reported reactions had higher prebooster titer of anti-S1 antibodies compared to those who reported no reactions.

The importance of tissue-based assay in the diagnosis of autoimmune encephalitis.

BACKGROUND: The evaluation of autoimmune encephalitis (AIE) usually includes antibody testing with commercial kits capable of detecting only preselected antibodies. A non-antigen-specific assay may help detect other antibodies. In this study, we evaluate the utility and clinical relevance of an immunofluorescence assay (IFA) in the evaluation of AIE. METHODS: Immunofluorescence assay was performed on 1949 patients' serum/CSF between 2017 and 2020 and clinical relevance was designated to each case based on clinical course, suggested criteria and ancillary testing. RESULTS: Sixty-one patients (3.1%) had positive serum IFA, positive CSF, or both. Twenty-eight out of 42 patients who were positive only on IFA were designated as clinically relevant (67%), 8 inconclusive (19%), and 6 non-relevant (14%). Pleocytosis was significantly higher in the clinically relevant cases (74% vs. 20% for non-clinically relevant cases). Encephalopathy was the most common presentation (36%), followed by cerebellar syndrome (32%) and seizures (25%). The initial diagnosis changed due to IFA results in 13/28 (46%) cases and IFA result led to the initiation or modification of treatment in all cases (68% and 43%, respectively). Twenty-five patients were treated with 1st line immunotherapy and 12 with 2nd line immunotherapy, with 92% responding to treatment. Twenty-six clinically relevant patients underwent cancer workup: seven (25%) had confirmed malignancy and three had high suspicion of malignancy (total of 37%). CONCLUSION: Non-antigen-specific assays, such as IFA, can identify antibodies not detected in commercially available kits and therefore are recommended in the evaluation of autoimmune encephalitis.

Technologies bringing young Zebrafish from a niche field to the limelight.

Fundamental life science and pharmaceutical research are continually striving to provide physiologically relevant context for their biological studies. Zebrafish present an opportunity for high-content screening (HCS) to bring a true in vivo model system to screening studies. Zebrafish embryos and young larvae are an economical, human-relevant model organism that are amenable to both genetic engineering and modification, and direct inspection via microscopy. The use of these organisms entails unique challenges that new technologies are overcoming, including artificial intelligence (AI). In this perspective article, we describe the state-of-the-art in terms of automated sample handling, imaging, and data analysis with zebrafish during early developmental stages. We highlight advances in orienting the embryos, including the use of robots, microfluidics, and creative multi-well plate solutions. Analyzing the micrographs in a fast, reliable fashion that maintains the anatomical context of the fluorescently labeled cells is a crucial step. Existing software solutions range from AI-driven commercial solutions to bespoke analysis algorithms. Deep learning appears to be a critical tool that researchers are only beginning to apply, but already facilitates many automated steps in the experimental workflow. Currently, such work has permitted the cellular quantification of multiple cell types in vivo, including stem cell responses to stress and drugs, neuronal myelination and macrophage behavior during inflammation and infection. We evaluate pro and cons of proprietary versus open-source methodologies for combining technologies into fully automated workflows of zebrafish studies. Zebrafish are poised to charge into HCS with ever-greater presence, bringing a new level of physiological context.

Unraveling a Nosocomial Outbreak of COVID-19: The Role of Whole-Genome Sequence Analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic poses many epidemiological challenges. The investigation of nosocomial transmission is usually performed via thorough investigation of an index case and subsequent contact tracing. Notably, this approach has a subjective component, and there is accumulating evidence that whole-genome sequencing of the virus may provide more objective insight. METHODS: We report a large nosocomial outbreak in 1 of the medicine departments in our institution. Following intensive epidemiological investigation, we discovered that 1 of the patients involved was suffering from persistent COVID-19 while initially thought to be a recovering patient. She was therefore deemed to be the most likely source of the outbreak. We then performed whole-genome sequencing of the virus of 14 infected individuals involved in the outbreak. RESULTS: Surprisingly, the results of whole-genome sequencing refuted our initial hypothesis. A phylogenetic tree of the samples showed multiple introductions of the virus into the ward, 1 of which led to a cluster of 10 of the infected individuals. Importantly, the results pointed in the direction of a specific index patient that was different from the 1 that arose from our initial investigation. CONCLUSIONS: These results underscore the important added value of using whole-genome sequencing in epidemiological investigations as it may reveal unexpected connections between cases and aid in understanding transmission dynamics, especially in the setting of a pandemic where multiple possible index cases exist simultaneously.

Antibiotic Use during the COVID-19 Pandemic in a Tertiary Hospital with an Ongoing Antibiotic Stewardship Program.

During the recent pandemic, the fact that the clinical manifestation of COVID-19 may be indistinguishable from bacterial infection, as well as concerns of bacterial co-infection, have been associated with an increased use of antibiotics. The objective of this study was to assess the effect of targeted antibiotic stewardship programs (ASP) on the use of antibiotics in designated COVID-19 departments and to compare it to the antibiotic use in the equivalent departments in the same periods of 2018 and 2019. Antibiotic consumption was assessed as days of treatment (DOT) per 1000 patient days (PDs). The COVID-19 pandemic was divided into three periods (waves) according to the pandemic dynamics. The proportion of patients who received at least one antibiotic was significantly lower in COVID-19 departments compared to equivalent departments in 2018 and 2019 (Wave 2: 30.2% vs. 45.6% and 44.9%, respectively; Wave 3: 30.5% vs. 47.8% and 50.1%, respectively, p < 0.001). The DOT/1000PDs in every COVID-19 wave was lower than during similar periods in 2018 and 2019 (179-282 DOT/1000PDs vs. 452-470 DOT/1000PDs vs. 426-479 DOT/1000PDs, respectively). Moreover, antibiotic consumption decreased over time during the pandemic. In conclusion, a strong ASP is effective in restricting antibiotic consumption, particularly for COVID-19 which is a viral disease that may mimic bacterial sepsis but has a low rate of concurrent bacterial infection.

A versatile, automated and high-throughput drug screening platform for zebrafish embryos.

Zebrafish provide a unique opportunity for drug screening in living animals, with the fast-developing, transparent embryos allowing for relatively high-throughput, microscopy-based screens. However, the limited availability of rapid, flexible imaging and analysis platforms has limited the use of zebrafish in drug screens. We have developed an easy-to-use, customisable automated screening procedure suitable for high-throughput phenotype-based screens of live zebrafish. We utilised the WiScan® Hermes High Content Imaging System to rapidly acquire brightfield and fluorescent images of embryos, and the WiSoft® Athena Zebrafish Application for analysis, which harnesses an Artificial Intelligence-driven algorithm to automatically detect fish in brightfield images, identify anatomical structures, partition the animal into regions and exclusively select the desired side-oriented fish. Our initial validation combined structural analysis with fluorescence images to enumerate GFP-tagged haematopoietic stem and progenitor cells in the tails of embryos, which correlated with manual counts. We further validated this system to assess the effects of genetic mutations and X-ray irradiation in high content using a wide range of assays. Further, we performed simultaneous analysis of multiple cell types using dual fluorophores in high throughput. In summary, we demonstrate a broadly applicable and rapidly customisable platform for high-content screening in zebrafish. This article has an associated First Person interview with the first author of the paper.

Spotted Fever Group Rickettsioses in Israel, 2010-2019.

In a multicenter, nationwide, retrospective study of patients hospitalized with spotted fever group rickettsiosis in Israel during 2010-2019, we identified 42 cases, of which 36 were autochthonous. The most prevalent species was the Rickettsia conorii Israeli tick typhus strain (n = 33, 79%); infection with this species necessitated intensive care for 52% of patients and was associated with a 30% fatality rate. A history of tick bite was rare, found for only 5% of patients; eschar was found in 12%; and leukocytosis was more common than leukopenia. Most (72%) patients resided along the Mediterranean shoreline. For 3 patients, a new Rickettsia variant was identified and had been acquired in eastern, mountainous parts of Israel. One patient had prolonged fever before admission and clinical signs resembling tickborne lymphadenopathy. Our findings suggest that a broad range of Rickettsia species cause spotted fever group rickettsiosis in Israel.

Herpes zoster following BNT162b2 mRNA COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: a case series.

OBJECTIVES: As global vaccination campaigns against COVID-19 disease commence, vaccine safety needs to be closely assessed. The safety profile of mRNA-based vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) is unknown. The objective of this report is to raise awareness of reactivation of herpes zoster (HZ) following the BNT162b2 mRNA vaccination in patients with AIIRD. METHODS: The safety of the BNT162b2 mRNA vaccination was assessed in an observational study monitoring post-vaccination adverse effects in patients with AIIRD (n = 491) and controls (n = 99), conducted in two rheumatology departments in Israel. RESULTS: The prevalence of HZ was 1.2% (n = 6) in patients with AIIRD compared with none in controls. Six female patients aged 49 ± 11 years with stable AIIRD: RA (n = 4), Sjogren's syndrome (n = 1), and undifferentiated connective disease (n = 1), developed the first in a lifetime event of HZ within a short time after the first vaccine dose in five cases and after the second vaccine dose in one case. In the majority of cases, HZ infection was mild, except a case of HZ ophthalmicus, without corneal involvement, in an RA patient treated with tofacitinib. There were no cases of disseminated HZ disease or postherpetic neuralgia. All but one patient received antiviral treatment with a resolution of HZ-related symptoms up to 6 weeks. Five patients completed the second vaccine dose without other adverse effects. CONCLUSION: Epidemiologic studies on the safety of the mRNA-based COVID-19 vaccines in patients with AIIRD are needed to clarify the association between the BNT162b2 mRNA vaccination and reactivation of zoster.