Fecal Microbiota Transplantation in Inflammatory Bowel Disease.

Inflammatory bowel diseases represent a complex array of diseases of incompletely known etiology that led to gastrointestinal tract chronic inflammation. In inflammatory bowel disease, a promising method of treatment is represented by fecal microbiota transplantation (FMT), FMT has shown its increasing effectiveness and safety in recent years for recurrent CDI; moreover, it showed real clinical benefits in treating SARS-CoV-2 and CDI co-infection. Crohn's disease and ulcerative colitis are characterized by immune dysregulation, resulting in digestive tract damage caused by immune responses. Most current therapeutic strategies are associated with high costs and many adverse effects by directly targeting the immune response, so modifying the microbial environment by FMT offers an alternative approach that could indirectly influence the host's immune system in a safe way. Studies outline the endoscopic and clinical improvements in UC and CD in FMT patients versus control groups. This review outlines the multiple benefits of FMT in the case of IBD by improving patients unbalanced gut, therefore improving endoscopic and clinical symptomatology. We aim to emphasize the clinical importance and benefits of FMT in order to prevent flares or complications of IBD and to highlight that further validation is needed for establishing a clinical protocol for FMT in IBD.

A Randomized Clinical Trial of Regdanvimab in High-Risk Patients With Mild-to-Moderate Coronavirus Disease 2019.

Background: We evaluated clinical effectiveness of regdanvimab (CT-P59), a severe acute respiratory syndrome coronavirus 2 neutralizing monoclonal antibody, in reducing disease progression and clinical recovery time in patients with mild-to-moderate coronavirus disease 2019 (COVID-19), primarily Alpha variant. Methods: This was phase 3 of a phase 2/3 parallel-group, double-blind, randomized clinical trial. Outpatients with mild-to-moderate COVID-19 were randomized to single-dose regdanvimab 40 mg/kg (n = 656) or placebo (n = 659), alongside standard of care. The primary endpoint was COVID-19 disease progression up to day 28 among "high-risk" patients. Key secondary endpoints were disease progression (all randomized patients) and time to recovery (high-risk and all randomized patients). Results: Of 1315 randomized patients, 880 were high risk; the majority were infected with Alpha variant. The proportion with disease progression was lower (14/446, 3.1% [95% confidence interval {CI}, 1.9%-5.2%] vs 48/434, 11.1% [95% CI, 8.4%-14.4%]; P < .001) and time to recovery was shorter (median, 9.27 days [95% CI, 8.27-11.05 days] vs not reached [95% CI, 12.35-not calculable]; P < .001) with regdanvimab than placebo. Consistent improvements were seen in all randomized and non-high-risk patients who received regdanvimab. Viral load reductions were more rapid with regdanvimab. Infusion-related reactions occurred in 11 patients (4/652 [0.6%] regdanvimab, 7/650 [1.1%] placebo). Treatment-emergent serious adverse events were reported in 5 of (4/652 [0.6%] regdanvimab and 1/650 [0.2%] placebo). Conclusions: Regdanvimab was an effective treatment for patients with mild-to-moderate COVID-19, significantly reducing disease progression and clinical recovery time without notable safety concerns prior to the emergence of the Omicron variant. Clinical Trials Registration: NCT04602000; 2020-003369-20 (EudraCT).

A Randomized Clinical Trial of Regdanvimab in High-Risk Patients with Mild-to-Moderate COVID-19

Background We evaluated clinical effectiveness of regdanvimab (CT-P59), a SARS-CoV-2 neutralizing monoclonal antibody, in reducing disease progression and clinical recovery time in patients with mild-to-moderate COVID-19, primarily alpha variant. Methods This was phase 3 of a phase 2/3 parallel-group, double-blind, randomized clinical trial. Outpatients with mild-to-moderate COVID-19, were randomized to single dose regdanvimab 40 mg/kg (n = 656) or placebo (n = 659), alongside standard-of-care. Primary endpoint: COVID-19 disease progression (clinical symptoms requiring hospitalization or oxygen therapy, or mortality) up to day 28 among “high risk” patients. Key secondary endpoints: disease progression (all randomized patients) and time to recovery (high-risk and all randomized patients). Results Of 1315 patients randomized to regdanvimab or placebo, 880 were high risk (regdanvimab, n = 446;placebo, n = 434);the majority (regdanvimab, n = 371;placebo n = 381) were infected with alpha variant. The proportion with disease progression was lower (14/446 [3.1%;95% CI, 1.9–5.2] vs. 48/434 [11.1%;95% CI, 8.4–14.4];P < 0.001) and time to recovery was shorter (median, 9.27 days [95% CI, 8.27–11.05] vs. not reached [95% CI, 12.35–not calculable];P < 0.001) with regdanvimab than placebo. Consistent improvements were seen in all randomized and non–high-risk patients who received regdanvimab. Viral load reductions were more rapid with regdanvimab. Infusion-related reactions occurred in 11/1302 patients (4/652 [0.6%] regdanvimab, 7/650 [1.1%] placebo). Treatment-emergent serious adverse events were reported in 5/1302 patients (4 [0.6%] regdanvimab, 1 [0.2%] placebo). Conclusions Regdanvimab was an effective treatment for patients with mild-to-moderate COVID-19, significantly reducing disease progression and clinical recovery time without notable safety concerns prior to the emergence of the omicron variant. Trial registration ClinicalTrials.gov identifier, NCT04602000;EudraCT number, 2020-003369-20

Longitudinal determination of BNT162b2 vaccine induced strongly binding SARS-CoV-2 IgG antibodies in a cohort of Romanian healthcare workers.

Mass vaccination against the disease caused by the novel coronavirus (COVID-19) was a crucial step in slowing the spread of SARS-CoV-2 in 2021. Even in the face of new variants, it still remains extremely important for reducing hospitalizations and COVID-19 deaths. In order to better understand the short- and long-term dynamics of humoral immune response, we present a longitudinal analysis of post-vaccination IgG levels in a cohort of 166 Romanian healthcare workers vaccinated with BNT162b2 with weekly follow-up until 35 days past the first dose and monthly follow-up up to 6 months post-vaccination. A subset of the patients continued with follow-up after 6 months and either received a booster dose or got infected during the Delta wave in Romania. Tests were carried out on 1694 samples using a CE-marked IgG ELISA assay developed in-house, containing S1 and N antigens of the wild type virus. Participants infected with SARS-CoV-2 before vaccination mount a quick immune response, reaching peak IgG levels two weeks after the first dose, while IgG levels of previously uninfected participants mount gradually, increasing abruptly after the second dose. Overall higher IgG levels are maintained for the previously infected group throughout the six month primary observation period (e.g. 36-65 days after the first dose, the median value in the previously infected group is 5.29 AU/ml, versus 3.58 AU/ml in the infection naïve group, p less than 0.001). The decrease of IgG levels is gradual, with lower median values in the infection naïve cohort even 7-8 months after vaccination, compared to the previously infected cohort (0.7 AU/ml versus 1.29 AU/ml, p = 0.006). Administration of a booster dose yielded higher median IgG antibody levels than post second dose in the infection naïve group and comparable levels in the previously infected group.

Is SARS-CoV-2 Directly Responsible for Cardiac Injury? Clinical Aspects and Postmortem Histopathologic and Immunohistochemical Analysis.

Myocardial injury in patients with SARS-CoV-2 infection may be attributed to the presence of the virus at the cellular level, however, it may also be secondary to other diseases, playing an essential role in the evolution of the disease. We evaluated 16 patients who died because of SARS-CoV-2 infection and analyzed the group from both clinical and pathological points of view. All autopsies were conducted in the Sibiu County morgue, taking into consideration all the national protocols for COVID-19 patients. Of the 16 autopsies we performed, two were complete, including an extensive examination of the cranial cavity. In our study, the cardiac injury was primarily cumulative. Chronic cardiac injuries included fatty infiltration of the myocardium in five cases, fibrosis in 11 cases, and coronary atherosclerosis in two cases. Among the cases with evidence of acute cardiovascular injuries, inflammatory lymphocytic infiltrate was observed in nine cases, subepicardial or visceral pericardial neutrophil-rich vascular congestion in five cases, and venous thrombosis in three cases. Acute ischemia or myocytic distress was identified by vacuolar degeneration in four cases; areas of undulated and/or fragmented myocardial fibers, with eosinophilia and nuclear pyknosis with or without enucleation of the myocytes in nine cases; and in one case, we observed a large area of myocardial necrosis. Immunohistochemical criteria confirmed the presence of the SARS-CoV-2 antigen at the level of the myocardium in only two cases. Comorbidities existing prior to SARS-CoV-2 infection associated with systemic and local inflammatory, thrombotic, hypoxic, or immunological phenomena influence the development of cardiac lesions, leading to death.

Our experience with 80 cases of SARS-CoV-2-Clostridioides difficile co-infection: An observational study.

Beside the changes in the gut microbiota in context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the increased use of high-risk broad-spectrum antibiotics during the actual pandemic raises concerns about a possible increase of Clostridioides difficile infections (CDIs). We retrospectively analyzed 80 consecutive patients, with SARS-CoV-2 pneumonia and CDI. The mean length of hospitalization was 19.63 days. The mean time of the onset of the digestive symptoms related to CDI was 5.16 days. Patients with an onset of the digestive symptoms from hospital admission have a significantly lower median length in hospital stay. The recovered patients present a statistically significant decreased median age. coronavirus disease 2019 (COVID-19) cured patients present CDI symptoms much earlier than the deceased patients, when comparing the median days before the occurrence of any digestive symptoms regarding CDI. Among the patients that prior to their hospitalization for COVID-19 were exposed to antibiotics, 54.7% presented CDI digestive symptoms during their hospitalization and 65.6% had a severe or critical COVID-19 form. Although the incidence of CDI in the pandemic is lower compared to the period before the pandemic, the severity of cases and the death rate increased. In the actual setting clinicians need to be aware of possible CDI and SARS-CoV-2 co-infection.

Is SARS-CoV-2 Directly Responsible for Cardiac Injury? Clinical Aspects and Postmortem Histopathologic and Immunohistochemical Analysis

Myocardial injury in patients with SARS-CoV-2 infection may be attributed to the presence of the virus at the cellular level, however, it may also be secondary to other diseases, playing an essential role in the evolution of the disease. We evaluated 16 patients who died because of SARS-CoV-2 infection and analyzed the group from both clinical and pathological points of view. All autopsies were conducted in the Sibiu County morgue, taking into consideration all the national protocols for COVID-19 patients. Of the 16 autopsies we performed, two were complete, including an extensive examination of the cranial cavity. In our study, the cardiac injury was primarily cumulative. Chronic cardiac injuries included fatty infiltration of the myocardium in five cases, fibrosis in 11 cases, and coronary atherosclerosis in two cases. Among the cases with evidence of acute cardiovascular injuries, inflammatory lymphocytic infiltrate was observed in nine cases, subepicardial or visceral pericardial neutrophil-rich vascular congestion in five cases, and venous thrombosis in three cases. Acute ischemia or myocytic distress was identified by vacuolar degeneration in four cases;areas of undulated and/or fragmented myocardial fibers, with eosinophilia and nuclear pyknosis with or without enucleation of the myocytes in nine cases;and in one case, we observed a large area of myocardial necrosis. Immunohistochemical criteria confirmed the presence of the SARS-CoV-2 antigen at the level of the myocardium in only two cases. Comorbidities existing prior to SARS-CoV-2 infection associated with systemic and local inflammatory, thrombotic, hypoxic, or immunological phenomena influence the development of cardiac lesions, leading to death.

Association of hiccup and SARS-CoV-2 infection with the administration of dexamethasone: a case report.

Introduction: Among the less common symptoms associated with the SARS-CoV-2 infection the attention is drawn by a persistent hiccup that was recently quoted in the literature. Case report: We present the case of a 46-year-old Caucasian male patient hospitalized in the Infectious Diseases Clinic of the Academic Emergency Hospital Sibiu, Romania with laboratory confirmation of SARS-CoV-2 infection with a positive result of real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay from nasopharyngeal swabs, that during the disease course developed persistent hiccup associated with the administration of cortisone therapy, dexamethasone. A decision to stop the treatment with cortisone preparations was made, with the disappearance of the hiccup after 36 hours. Conclusions: From our experience, other cases of SARS-CoV-2 infection that we managed during these months of the pandemic, with mild or severe forms of the disease, showed hiccup under treatment with dexamethasone, an event also described in other medical conditions under the same treatment and improved at its cessation or when replaced by methylprednisolone.

Off-label tocilizumab and adjuvant iron chelator effectiveness in a group of severe COVID-19 pneumonia patients: A single center experience.

ABSTRACT: Tocilizumab (TCZ), a monoclonal recombinant antibody against IL-6 receptor, is currently used in managing the cytokine release syndrome (CRS) that occurred in coronavirus disease 2019 (COVID-19) selected cases. The primary objective of our study was to establish the effectiveness of TCZ in patients with severe or critical severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia.We retrospectively analyzed 25 consecutive patients, admitted in the Academic Emergency Hospital Sibiu, Romania from April 1, 2020 until May 25, 2020, all with confirmed SARS-CoV-2 infection and severe pneumonia. All patients were treated off-label with TCZ, beside their standard care. Adjuvant iron chelator was associated in 11 patients.Six female and 19 male patients admitted in our hospital all with confirmed SARS-CoV-2 infection and severe pneumonia as defined by Chinese Centers for Disease Control and Prevention were enrolled in this study. Seventeen of the 25 enrolled patients (68%) were seriously ill requiring noninvasive ventilation or oxygen mask, and 8 cases (32%) were critically ill requiring invasive mechanical ventilation. All patients received TCZ, and also received hydroxychloroquine, and lopinavir/ritonavir 200/50 mg for 10 days. Adjuvant iron chelator (deferasirox - marketed as Exjade) was associated in 11 patients who had ferritin serum levels above 1000 ng/mL. No side effects were encountered during infusions or after TCZ. We observed a rapid increase in arterial oxygen saturation for 20 of the 25 cases (80%) with a favorable evolution toward healing. Survivors were younger than 60 years old (80%), had less comorbidities (10% no comorbidities, 70% with 1 or 2 comorbidities), lower serum ferritin levels (30% under 1000 ng/mL), and 50% had no serum glucose elevation. Our patients with CRS had no response to corticosteroid therapy. Five out of the 25 patients had an unfavorable evolution to death. The off-label use of TCZ in patients with severe or critically ill form of SARS-CoV-2 infection had good results in our study.Off-label use of TCZ in severe and critical cases of COVID-19 pneumonia is effective in managing the "cytokine storm." Better outcomes were noted in younger patients. Associated adjuvant iron chelators may contribute to a good outcome and needs to be confirmed in larger studies.

Cutaneous manifestations associated with anosmia, ageusia and enteritis in SARS-CoV-2 infection - A possible pattern? Observational study and review of the literature.

BACKGROUND: The cutaneous manifestations of coronavirus disease 2019 (COVID-19) have been covered insufficiently in the literature. METHODS: Thirty-nine patients admitted to the study hospital with confirmed COVID-19 who experienced various skin manifestations during hospitalization or in the convalescence period, were analysed retrospectively. RESULTS: Thirty-nine patients with COVID-19, admitted to the study hospital between 23 March and 12 September 2020, had intra-infectious rash or lesions of cutaneous vasculitis during convalescence. The most common cutaneous manifestations of COVID-19 were erythematous and erythematous papular rash. Twenty-seven of the 39 patients had anosmia (69.2%), 26 patients had ageusia (66.7%), 34 patients had pneumonia (87.2%) and 24 patients had intra-infectious enterocolitis (61.5%). Skin biopsies were rarely performed in these patients. This article reports the results of biopsies performed in two patients, showing histopathological and immunohistochemical changes in erythematous rash and erythema multiforme-like lesions. Both skin biopsies revealed early fibrous remodelling of the dermis, suggesting similarity with changes that occur in the lungs and other tissues in patients with COVID-19. CONCLUSIONS: Correlations between skin lesions and anosmia, ageusia and enteritis in patients with COVID-19 do not seem to be accidental, but are associated with a similar response to ACE2 receptor expression in these tissues.

Pityriasis rosea Gibert triggered by SARS-CoV-2 infection: A case report.

RATIONALE: Pityriasis rosea Gibert is an erythematous-papulosquamous dermatosis that frequently occurs in young adults. The etiopathogenesis of PR is still unknown, but is frequently associated with episodes of upper respiratory tract infections. It is likely that a new viral trigger of pityriasis rosea is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PATIENT CONCERNS: We present the case of a female patient in whom the diagnosis of pityriasis rosea led to the investigation and diagnosis of the SARS-CoV-2 infection. The patient presented to the Department of Dermatology for a 3 week duration of an extremely pruritic erythematous-squamous lesion, initially on the trunk and upper limbs, with extension to the lower limbs in the last week and the lesion respected the cephalic extremity, palms, and soles. One week before the rash, respiratory tract infection symptomatology was observed by the patient. At home, she underwent systemic treatment with antihistamines and topical medication with dermatocorticosteroids. The evolution was unfavorable, with the spread of the lesions and the accentuation of the pruritus. DIAGNOSES: Considering the actual epidemiological context, we performed a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay from nasal and pharyngeal swabs for coronavirus disease 2019 (COVID-19) to investigate the PR etiology. The patient had a positive RT-PCR result, and was confirmed with SARS-CoV-2 infection. INTERVENTIONS: Treatment was initiated with systemic corticosteroid therapy - hydrocortisone hemisuccinate 200 mg/day for 7 days, and loratadine 10 mg 2 times a day. Also, topical medication with dermatocorticosteroids and emollients was associated. OUTCOME: Under the treatment that was initiated a partial remission of the lesions after 7 days was observed. LESSONS: Our reported case adds to the other findings regarding the association of PR with SARS-CoV-2 infection, in the context of the pandemic, suggesting the need to test patients with PR skin lesions for SARS-CoV-2 infection.

Viral exanthema as manifestation of SARS-CoV-2 infection: A case report.

RATIONALE: The clinical manifestations of the SARS-CoV-2 infection are mainly respiratory but the virus can cause a variety of symptoms. Dermatological findings are less well-characterized. Data is scarce on their timing, type and correlation with the immune response. PATIENT CONCERNS: We present the case of SARS-CoV-2 infection in a previously healthy woman who presented with respiratory symptoms and developed anosmia, diarrhea, and an erythematous maculo-papular rash on day 15 from symptom onset. DIAGNOSIS: The nasopharyngeal swab tested by real time PCR for COVID-19 was positive. We interpreted this as a viral exanthema likely caused by an immune response to SARS-CoV-2 nucleotides. INTERVENTIONS: She was treated with Hydroxychloroquine, Azithromycin and Lopinavir/Ritonavir, and the rash with topical corticosteroids. OUTCOMES: All symptoms resolved except for anosmia which persisted for 6 weeks. At the 4- and 6-weeks follow-up the IgG titers for SARS-CoV-2 were high. LESSONS: We must consider that SARS-CoV-2 has a multi-organ tropism. In our case, the SARS-CoV-2 infection had lung, nasopharyngeal, neurological, digestive, and skin manifestations. Identifying the different manifestations is useful for understanding the extent of SARS-CoV-2 infection. We not only present a rare manifestation but also suggest that cutaneous manifestations may correlate with immunity.

SARS-CoV-2 infection associated with micturition syncope: Our experience with 4 case reports.

RATIONALE: Syncope is described as the loss of consciousness and postural muscle tone with a short duration and fast onset. Micturition syncope can be caused by abnormal vasovagal response or by the dysfunction of the blood pressure regulating mechanism, which occurs before, during, or immediately after urination. PATIENT CONCERNS: We present 4 cases of COVID-19 hospitalized in the Department of Infectious Diseases of the Academic Emergency Hospital Sibiu, Romania, cases that presented micturition syncope. DIAGNOSES: During hospitalization, patients confirmed with SARS-Cov-2 infection using real time reverse transcriptase-polymerase chain reaction (RT-PCR) assay, presented micturition syncope in different stages of the infection (at the beginning and in the second week of evolution). INTERVENTIONS: Other causes of syncope such as adrenal insufficiency secondary to corticosteroids treatment, cardiac rhythm disorders, neurological impairment, dehydration, vasoactive medication, malignancies, pulmonary hypertension and coughing were excluded. The treatment of SARS-CoV-2 infection was performed following the local and national guidelines. OUTCOMES: The clinical course of all 4 patients diagnosed with COVID-19 and micturition syncope was favorable. To our knowledge, micturition syncope in COVID-19 patients has yet not been reported by other authors. LESSONS: To our knowledge, micturition syncope associated with the evolution of COVID-19, has yet not been reported by other authors.