Hidden Danger of Sars-Cov-2, Multisystem Inflammatory Syndrome in Adults (Mis-a): First Case Series in a Single Center from Turkiye

Objective: Multisystem Inflammatory Syndrome (MIS) is a con-dition seen in the early post-COVID-19 period and thought to develop with an impaired immune response. It has been usually reported in children but rarely in adults. Here we report the first MIS-A case series from Turkiye.Material and Methods: Six patients who met the Centers for Disease Control and Preventions MIS-A diagnostic criteria were included in the study. The demographic, clinical, laboratory, ra-diological characteristics and therapy regimes and outcomes of the patients were recorded.Results: All of our cases had a history of mild COVID-19. They presented with fever, severe fatigue and hypotension. Abnormal echocardiography findings were detected in five patients. Only one patient had multiple mucocutaneous findings. Common lab-oratory features were lymphopenia, markedly increased C-Reak-tive Protein, procalcitonin, pro-brain natriuretic peptide (pro-BNP), D-dimer, and ferritin. All patients had positive SARS-CoV-2 antibody result. Corticosteroids and/or anakinra were used in five, Intravenous immunoglobulin was used in two patients. Low-mo-lecular-weight heparin (LMWH) was used for all cases. Empirically initiated antibiotic treatments were discontinued after cultures were negative. After anti-inflammatory treatment, the hypoten-sion of the patients resolved, they did not need intensive care follow-up and no mortality was seen in our cases.Conclusions: MIS-A is a severe and mortal condition that causes various clinical pictures and can be confused with sepsis. Anakin-ra, a recombinant IL-1 receptor antagonist, is a significant agent that can be used in the treatment of MIS-A since it blocks the cytokine cascade at an early stage. The satisfactory respons-es will be obtained with early diagnosis and anti-inflammatory treatment. In this period when the pandemic is not over yet, it is necessary to increase the awareness of clinicians about MIS-A, which can be fatal.

PATIENT CHARACTERISTICS AND RISK FACTORS FOR MORTALITY IN 504 HOSPITALIZED PATIENTS DUE TO COVID-19

Objective: In this study, we aimed to analyze the demographic characteristics, symptoms, and comorbidities of 504 patients hospitalized for COVID-19. We also sought to describe the relationship between these features and intensive care unit (ICU) admission and mortality. Materials and Methods: This study is a descriptive study involving 504 COVID-19 patients hospitalized between 16.03.2020 and 07.05.2020 at Istanbul Universitys’ Istanbul Faculty of Medicine Hospital. Information about the patients was obtained from the hospital automation system and evaluated retrospectively. Results: The average age of the 504 patients was 56±15.14, and 59.1% of them were male. The proportion of the patients admitted into ICU 11.9% and for 8.52% of them the disease resulted in death. Real time polymerase chain reaction (RT-PCR) test results were positive for 60.5% of the patients. The median time spent in the hospital was eight days. Fifty six percent of the patients had at least one accompanying comorbid disease, with hypertension (39.3%) and diabetes (20.8%) being the most common. Being 65 years old or older (p<0.001), days spent in the hospital (p<0.001), presence of at least one comorbidity (p=0.009), hypertension (p=0.003), coronary artery disease (p=0.004), congestive heart failure (p=0.005) and dyspnea (p<0.001) were all factors found in those admitted to ICU. Conclusion: COVID-19 infection leading to high morbidity-mortality rates and an increased requirement for ICU admission is mainly seen among older patients and those who have dyspnea. During the process of analyzing patients suspected of COVID-19 who are admitted to hospital, it is crucial to consider both the patient’s age and any respiratory symptoms. Such a clinical evaluation is crucial for a better understanding of the course of the disease. (English) [ FROM AUTHOR] Amaç: Bu araştırmada, COVID-19 nedeniyle tedavi almak üzere hastaneye yatırılan 504 hastanın demografik özellikleri, semptomları ve komorbiditeleri incelenerek;bu özelliklerin yoğun bakım ünitesine yatış ve mortalite ile ilişkisini ortaya koymak amaçlanmıştır. Gereç ve Yöntem: Bu araştırma, 16.03.2020-07.05.2020 tarihleri arasında COVID-19 tedavisi almak üzere Ístanbul Üniversitesi Ístanbul Tıp Fakültesi Hastanesi’ne yatırılan 504 hastanın dahil edildiği tanımlayıcı tipte bir araştırmadır. Hastalara ait bilgiler hastane otomasyon sisteminden alınarak retrospektif olarak değerlendirilmiştir. Bulgular: Beşyüz dört hastanın yaş ortalaması 56±15,14 yıl, hastaların %59,1’i erkekti. Yoğun bakım ünitesine yatışı olan hastaların oranı %11,9;ölen hastaların oranı %8,52 idi. Hastaların %60,5’inin test sonucu pozitifti. Hastanede kalınan sürenin ortancası sekiz gündü. Hastaların %56’sının en az bir komorbid hastalığı vardı;hipertansiyon (%39,3) ve diyabet (%20,8) en sık eşlik eden komorbiditelerdi. Altmış beş yaş ve üzeri olmak (p<0,001), hastanede kalınan gün sayısı (p<0,001), en az bir komorbidite varlığı (p=0,009), hipertansiyon (p=0,003), koroner arter hastalığı (p=0,004), konjestif kalp yetmezliği (p=0,005) ve dispne (p<0,001), yoğun bakıma yatış ile ilişkili bulunmuştur. Sonuç: Yüksek morbidite-mortalite oranlarına ve yoğun bakım ünitesine yatış ihtiyacının artmasına neden COVID-19, özellikle yaşlı hastalarda ve dispnesi olan hastalarda daha yüksek mortalite oranlarına neden olmaktadır. Hastaneye başvuran COVID-19 şüpheli hastalar değerlendirilirken özellikle hastanın yaşı ve solunum sistemi semptomları göz önünde bulundurularak klinik değerlendirilmesinin yapılması hastalığın seyri açısından önem taşımaktadır. (Turkish) [ FROM AUTHOR] Copyright of Istanbul Tip Fakültesi Dergisi is the property of Istanbul Tip Fakultesi Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

[First Case of COVID-19 Positive Candida auris Fungemia in Turkey]. / Türkiye'de Ilk COVID-19 Pozitif Candida auris Fungemi Olgusu.

Candida auris is a species of fungus that has gained importance in recent years owing to its ability to cause hospital infections and epidemics, resistant to antifungal agents and disinfection processes and frequently misidentified by commercial systems. Hospital outbreaks caused by C.auris have been reported from some countries. It has been determined that C.auris has lower virulence than Candida albicans; however, it is associated with high mortality rates in immunocompromised individuals. An increase in the incidence of invasive fungal infections which can lead to serious complications and death, has been identified in severe coronavirus-2019 (COVID-19) patients or immunocompromised individuals with underlying disease. Studies demonstrated an increase in the frequency of C.auris isolation in COVID-19 patients with candidemia. In this report, the first case of COVID-19 positive C.auris fungemia detected in Turkey was presented. A 71-year-old male patient with a history of myocardial infarction, diabetes mellitus, donation of a single kidney and lobectomy surgery due to lung cancer was hospitalized in the pandemic thoracic surgery service due to the findings consistent with viral pneumonia on thoracic computed tomography. Favipiravir 2 x 600 mg and intravenous dexamethasone 1 x 6 mg therapy was administered. The patient tested positive for SARS-CoV-2 polymerase chain reaction, and severe involvement of the left lung was detected in the following days. Antibiotics were administered, followed by insertion of a right jugular vein catheter and initation of tocilizumab. The patient was transferred to the intensive care unit due to increased respiratory distress. Yeast growth was detected in the patient's hemoculture. The yeast strain could not be identified using API ID 32C (bioMerieux, France) (Sacchromyces kluyveri, Candida sake, unacceptable profile), but was identified as C.auris using the VITEK MALDI TOF MS (bioMerieux, France) (99.9%) system and confirmed by sequencing. The minimum inhibitor concentration values were detected as 3 µg/ml for amphotericin B; > 256 µg/ml for fluconazole; 0.19 µg/ml for voriconazole; 0.19 µg/ml for itraconazole; 0.016 µg/ml for posaconazole; 1 µg/ml for caspofungin and 0.094 µg/ml for anidulafungin by using the antibiotic gradient method. The patient's initial treatment comprised meropenem 3 x 1 g, vancomycin 2 x 1 g, caspofungin 1 x 70 mg, and continued as caspofungine 1 x 50 mg after the loading dose, and vancomycin 1 x 1 g/48 hours from the third day of treatment. The patient died on the ninth day after developing candidemia. The present case is the first case of fungemia caused by C.auris in a COVID-19 positive patient in Turkey, and it emphasizes the need of caution for fungemia due to C.auris in intensive care units in our country which has a high COVID-19 incidence.

Tocilizumab treatment in severe COVID-19: a multicenter retrospective study with matched controls.

Coronavirus disease-2019 (COVID-19) associated pneumonia may progress into acute respiratory distress syndrome (ARDS). Some patients develop features of macrophage activation syndrome (MAS). Elevated levels of IL-6 were reported to be associated with severe disease, and anti-IL-6R tocilizumab has been shown to be effective in some patients. This retrospective multicenter case-control study aimed to evaluate the efficacy of tocilizumab in hospitalized COVID-19 patients, who received standard of care with or without tocilizumab. Primary outcome was the progression to intubation or death. PSMATCH (SAS) procedure was used to achieve exact propensity score (PS) matching. Data from 1289 patients were collected, and study population was reduced to 1073 based on inclusion-exclusion criteria. The composite outcome was observed more frequently in tocilizumab-users, but there was a significant imbalance between arms in all critical parameters. Primary analyses were carried out in 348 patients (174 in each arm) after exact PS matching according to gender, ferritin, and procalcitonin. Logistic regression models revealed that tocilizumab significantly reduced the intubation or death (OR 0.40, p = 0.0017). When intubation is considered alone, tocilizumab-users had > 60% reduction in odds of intubation. Multiple imputation approach, which increased the size of the matched patients up to 506, provided no significant difference between arms despite a similar trend for intubation alone group. Analysis of this retrospective cohort showed more frequent intubation or death in tocilizumab-users, but PS-matched analyses revealed significant results for supporting tocilizumab use overall in a subset of patients matched according to gender, ferritin and procalcitonin levels.

Impairment of right ventricular longitudinal strain associated with severity of pneumonia in patients recovered from COVID-19.

Myocardial injury caused by COVID-19 was reported in hospitalized patients previously. But the information about cardiac consequences of COVID-19 after recovery is limited. The aim of the study was comprehensive echocardiography assessment of right ventricular (RV) in patients recovered from COVID-19. This is a prospective, single-center study. After recovery from COVID-19, echocardiography was performed in consecutive 79 patients that attended follow-up visits from July 15 to November 30, 2020. According to the recovery at home vs hospital, patients were divided into two groups: home recovery (n = 43) and hospital recovery (n = 36). Comparisons were made with age, sex and risk factor-matched control group (n = 41). In addition to conventional echocardiography parameters, RV global longitudinal strain (RV-GLS) and RV free wall strain (RV-FWS) were determined using 2D speckle-tracking echocardiography (2D STE). Of the 79 patients recovered from COVID-19, 43 (55%) recovered at home, while 36 (45%) required hospitalization. The median follow-up duration was 133  ±  35 (87-184) days. In patients recovered from hospital, RV-GLS and RV-FWS were impaired compared to control group (RV-GLS: -17.3  ±  6.8 vs. -20.4  ±  4.9, respectively [p = 0.042]; RV-FWS: -19.0  ±  8.2 vs. -23.4  ±  6.2, respectively [p = 0.022]). In subgroup analysis, RV-FWS was impaired in patients severe pneumonia (n = 11) compared to mild-moderate pneumonia (n = 28), without pneumonia (n = 40) and control groups (-15.8  ±  7.6 vs. -21.6  ±  7.6 vs. -20.8  ±  7.7 vs. -23.4  ±  6.2, respectively, [p = 0.001 for each]) and RV-GLS was impaired compared to control group (-15.2  ±  6.9 vs. -20.4  ±  4; respectively, [p = 0.013]). A significant correlation was detected between serum CRP level at hospital admission and both RV-GLS and RV-FWS (r = 0.285, p = 0.006; r = 0.294, p = 0.004, respectively). Age (OR 0.948, p = 0.010), male gender (OR 0.289, p = 0.009), pneumonia on CT (OR 0.019, p = 0.004), and need of steroid in treatment (OR 17.424, p = 0.038) were identifed as independent predictors of impaired RV-FWS (> -18) via multivariate analysis. We demonstrated subclinic dysfunction of RV by 2D-STE in hospitalized patients in relation to the severity of pneumonia after recovery from COVID-19. 2D-STE supplies additional information above standard measures of RV in this cohort and can be used in the follow-up of these patients.

Evaluation the relationship of left ventricular global longitudinal strain and laboratory parameters in discharged patients with COVID-19: a follow-up study.

BACKGROUND: The novel coronavirus infection (COVID-19) disease has spread rapidly and posed a great threat to global public health. The laboratory parameters and clinical outcomes of the disease in discharged patients remain unknown. In this study, we aimed to investigate the laboratory and echocardiographic findings of patients with COVID-19 after discharge and the relation between left ventricular global longitudinal strain (LVGLS) and inflammatory parameters in discharged patients. METHODS: A total of 75 patients recovering from COVID-19 as the study group were prospectively recruited from the COVID-19 outpatient clinic for their follow-up visits at a median 6 months after discharge. Patients were classified into groups according to pneumonia severity and impairment in LVGLS. Laboratory findings of patients both at admission and after discharge were evaluated and the relation with pneumonia severity at admission and LVGLS after discharge were analyzed. RESULTS: Serum ferritin, lactate dehydrogenase (LDH) and prohormone B-type natriuretic peptide (pro-BNP) levels after discharge were significantly higher in the study group than the control group (n = 44). Ferritin was found to be related to pneumonia severity. Serum ferritin and LDH values after discharge were significantly higher in patients with impaired LVGLS than those with preserved. There was a significant correlation between LVGLS, serum ferritin and LDH values after discharge (r = -0.252, p = 0.012; r = -0.268, p = 0.005, respectively). CONCLUSIONS: Clinicians should pay close attention to the serum ferritin and LDH levels in discharged patients for predicting the severity of COVID-19 disease and early identification of subclinical left ventricular myocardial dysfunction.

The effect of tocilizumab, anakinra and prednisolone on antibody response to SARS-CoV-2 in patients with COVID-19: A prospective cohort study with multivariate analysis of factors affecting the antibody response.

OBJECTIVES: Disease severity, previous medications and immunosuppressive agents could affect the antibody response against SARS-CoV-2. This study aimed to analyze variables affecting the humoral response to SARS-CoV-2. METHODS: This prospective cohort study included adult patients who recovered from COVID-19 and were admitted to a COVID-19 follow-up unit. Eight patient groups were defined in accordance with the results of thoracic computed tomography (CT), SARS-CoV-2 PCR test, and tocilizumab or anakinra use during active disease. Anti-S IgG antibodies were determined by ELISA in serum samples. Anti-S positive and negative cases were compared. RESULTS: A total of 518 patients were included in the study. SARS-CoV-2 IgG antibodies were positive in 82.8% of patients. SARS-CoV-2 PCR positivity, extent of lung involvement on CT, and time to antibody testing were independently associated with antibody positivity. Tocilizumab, anakinra or prednisolone use was not a factor affecting the antibody response. The rate of antibody response and sample/CO values among antibody-positive patients showed a linear relationship with the extent of lung involvement on CT. CONCLUSIONS: The use of tocilizumab, anakinra and prednisolone for COVID-19 did not affect the antibody response against SARS-CoV-2. The main driver of antibody response among patients with COVID-19 was the extent of pulmonary involvement on CT.