Remdesivir treatment for patients with moderate to severe COVID-19.

BACKGROUND: Remdesivir, which was first developed for the treatment of Ebola disease but failed to meet expectations, has become hope in the fight against the COVID-19 pandemic. This study aimed to evaluate risk factors for mortality and prognosis of adult moderate/severe COVID-19 patients treated with remdesivir, and safety and tolerability of 5 days of remdesivir treatment. METHODS: This multicenter prospective observational study was conducted in 14 centers in Turkey. Pregnancy or breastfeeding, multiorgan failure, or usage of vasopressors for septic shock, ALT > 5 × the upper limit of the normal range, or eGRF <30 mL/min or dialysis and receiving favipiravir were the exclusion criteria of the study. RESULTS: Among 500 patients, 494 patients were included in the study. On admission, 392 (79.3%) patients had moderate and 102 (20.6%) patients had severe COVID-19. The 28-day mortality was 10.1%. The median of the scores of the seven-category ordinal scale assessed on days 0, 3, 5, 7 were 4 and 3 on day 14. When the survival status of the patients was evaluated according to the time between the remdesivir start date and the end date of the symptoms, no statistically significant difference was found between the medians of the groups (p = 0.404). In multivariable analysis, age (OR, 1.05; 95%CI, 1.02-1.08; p = 0.003), SpO2 level on admission (OR, 3.03; 95%CI, 1.35-6.81; p = 0.007), heart rate (OR, 2.48; 95%CI, 1.01-6.07; p = 0.047), follow-up site at the hospital (clinic/ICU) (OR, 26.4; 95%CI, 11.6-60.17; p < 0.001) were independently associated with increased mortality. Grade 3 adverse event (AE) was observed in 4 (0.8%) patients. None of the patients experienced grade 4 or 5 AEs. DISCUSSION: Remdesivir is a safe and well-tolerated drug and older age, low SpO2 level on admission, tachycardia, and ICU admission are independently associated with increased mortality among patients with moderate/severe COVID-19 receiving remdesivir treatment.

Monitoring Crimean-Congo haemorrhagic fever virus RNA shedding in body secretions and serological status in hospitalised patients, Turkey, 2015.

IntroductionCrimean-Congo haemorrhagic fever (CCHF) is a tick-borne disease in Africa, Asia, the Balkan peninsula, the south-east of Europe and the Middle East, with mortality rates of 3-30%. Transmission can also occur through contact with infected animals or humans.AimThis observational, prospective case series aimed to investigate detectable viral genomic RNA in whole-body fluids and antibody dynamics in consecutive daily samples of patients diagnosed with CCHF until discharge from hospital.MethodsWe tested 18 patients and 824 swabs and sera with RT-PCR and 125 serum samples serologically.ResultsThe longest duration until clearance of viral RNA was 18 days from serum collection and 18, 15, 13, 19 and 17 days, respectively, from nasal, oral, genital (urethral or vaginal) and faecal swab, and urine. In seven patients, viral load decreased in serum at the same time as it increased in urine or persisted at the same logarithmic values. Despite clearance in serum, viral RNA was detected in faeces and genital swabs in two and three patients, respectively. Viral clearance from body fluids occurred earlier than from serum in eight patients on ribavirin treatment. The shortest seroconversion time was 3 days after symptom onset for IgM and IgG. Seroconversion of IgG occurred until Day 14 of symptoms.ConclusionWe report persistence of viral RNA in urine, faeces and genital swabs despite serum clearance. This may indicate a need for extending isolation precautions, re-evaluating discharge criteria and transmission risk after discharge, and considering oral swabs as a less invasive diagnostic alternative.

Cytokine response in crimean-congo hemorrhagic fever virus infection.

We described the predictive role of cytokines in fatality of Crimean Congo Hemorrhagic Fever Virus (CCHFV) infection by using daily clinical sera samples. Consequent serum samples of the selected patients in different severity groups and healthy controls were examined by using human cytokine 17-plex assay. We included 12 (23%) mild, 30 (58%) moderate, 10 (19%) severe patients, and 10 healthy volunteers. The mean age of the patients was 52 (sd 15), 52% were female. Forty-six patients (88%) received ribavirin. During disease course, the median levels of IL-6, IL-8, IL-10, IL-10/12, IFN-γ, MCP-1, and MIP-1b were found to be significantly higher among CCHF patients than the healthy controls. Within the first 5 days after onset of disease, among the fatal cases, the median levels of IL-6 and IL-8 were found to be significantly higher than the survived ones (Fig. 3), and MCP-1 was elevated among fatal cases, but statistical significance was not detected. In receiver operating characteristic (ROC) analysis, IL-8 (92%), IL-6 (92%), MCP-1 (79%) were found to be the most significant cytokines in predicting the fatality rates in the early period of the disease (5 days). IL-6 and IL-8 can predict the poor outcome, within the first 5 days of disease course. Elevated IL-6 and IL-8 levels within first 5 days could be used as prognostic markers.

Crimean-Congo hemorrhagic fever among health care workers, Turkey.

We investigated 9 cases of Crimean-Congo hemorrhagic fever (1 fatal, 2 asymptomatic) among health care workers in Turkey. Needlestick injuries were reported for 4 workers. Eight received ribavirin. In addition to standard precautions, airborne infection isolation precautions are essential during aerosol-generating procedures. For postexposure prophylaxis and therapy, ribavirin should be given.

Severity scoring index for Crimean-Congo hemorrhagic fever and the impact of ribavirin and corticosteroids on fatality.

BACKGROUND: Patients infected with Crimean-Congo hemorrhagic fever (CCHF) virus present with a wide clinical spectrum. In observational studies, the effects of therapeutic agents are confounded by severity. We describe use of a clinical severity scoring index (SSI) for CCHF patients and assess the effect of ribavirin and corticosteroid therapy on the case-fatality rate, stratified by SSI. METHODS: The study group included hospitalized patients who received a diagnosis of CCHF at the Infectious Diseases and Clinical Microbiology Clinic of Ankara Numune Education and Research Hospital between 2004 and 2011. The SSI included platelet count, bleeding, fibrinogen level, activated partial thromboplastin time, and somnolence. The effects of ribavirin and corticosteroid on the case-fatality rate were studied by univariate and multivariate analysis, stratified by SSI. RESULTS: Two hundred eighty-one confirmed cases of CCHF were included in the study. Of 281 patients, 23 (8%) died. The mean age (±SD) of the patients was 47 ± 16 years. Forty-nine percent were female. The mean duration of stay at our clinic after onset of symptoms was 4.4 days, with a range of 1-14 days. In multivariate analysis of factors for the prediction of death, the SSI (odds ratio [OR], 3.27; 95% confidence interval [CI], 2.09-5.13) and ribavirin use (OR, 0.04; 95% CI, .004-.48) were found to be statistically significant factors. CONCLUSION: The SSI is an accurate predictor of death and will therefore be a useful tool for case management and for drug-assessment studies. After stratification of cases by SSI, ribavirin was found to be effective in reducing the case-fatality rate, especially among moderately ill patients, whereas steroids were found to be beneficial particularly among patients with severe disease.

Neurobrucellosis: clinical and diagnostic features.

BACKGROUND: We describe the neurological involvement in brucellosis and revisited diagnostic criteria for neurobrucellosis. METHODS: Patients with laboratory-confirmed brucellosis who were consequently hospitalized were observed prospectively in a brucellosis-endemic region. The neurobrucellosis was diagnosed by any one of the following criteria: (1) symptoms and signs consistent with neurobrucellosis; (2) isolation of Brucella species from cerebrospinal fluid (CSF) and/or presence of anti-Brucella antibodies in CSF; (3) the presence of lymphocytosis, increased protein, and decreased glucose levels in CSF; or (4) diagnostic findings in cranial magnetic resonance imaging or CT. RESULTS: Lumbar puncture was performed in 128 laboratory-confirmed brucellosis cases who had neurological symptoms and signs, and 48 (37.5%) were diagnosed as neurobrucellosis. The sensitivity of tube agglutination (TA) in CSF was 0.94, specificity 0.96, positive predictive value 0.94, and negative predictive value 0.96. Brucella bacteria were isolated from CSF in 7 of 48 patients (15%). The mean age of 48 neurobrucellosis patients was 42 years (SD, 19 years), and 16 (33%) were female. The most common neurological findings were agitation (25%), behavioral disorders (25%), muscle weakness (23%), disorientation (21%), and neck rigidity (17%). Cranial nerves were involved in 9 of 48 patients (19%). One patient was left with a sequela of peripheral facial paralysis and 2 patients with sensorineural hearing loss. CONCLUSIONS: Patients with severe and persistent headache and other neurologic symptoms and signs should be considered for neurobrucellosis in endemic regions and to possibly receive longer therapy than 6 weeks. Brucella TA with Coombs test in CSF is sensitive and specific by using a cutoff of ≥1:8.

Evaluation of Blood Stream and Biliary Tract Infections Related to Percutaneous Transhepatic Cholangiography and Prophylaxis Given in Patients with Malignancy.

Objective: Percutaneous transhepatic cholangiography (PTC) is an invasive procedure used in patients with obstructive jaundice in the progress of some malignancies, and its most common complication is infection. We aimed to evaluate the patients who underwent PTC regarding their cultures, prophylaxis, and antibiotics used for treatment. Materials and Methods: In this cross-sectional study, patients who underwent PTC and were followed up in a medical oncology outpatient clinic between 2010-2017 were evaluated retrospectively. Patients' data were obtained from the hospital record system (FONET), epicrisis forms, and patient progress files. Results: A total of 93 patients were included in the study. Prophylaxis was given in 50% of the cases. Complications developed in 68% of the cases after the intervention, and the infectious disease clinic consulted all. Blood cultures were obtained from 89% of the febrile patients; however, bile cultures were obtained only from 29%. The rate of resistant Gram-negative enteric bacteria in growing microorganisms was 52% (n=13). It was determined that 65% of the initiated empirical treatments were appropriate for the growth of microorganisms. Conclusion: The growth rate was significantly higher in blood cultures than in bile cultures. The lower growth rate in bile culture was attributed to the low number of bile cultures. There was no significant difference regarding the growth rate and drug resistance of the microorganisms. Therefore, we think giving antibiotics as treatment rather than prophylaxis is more appropriate. Taking cultures will ensure that patients receive appropriate antibiotic therapy for the causative agent.

COVID-19 and Crimean-Congo Hemorrhagic Fever: Is there any Similarity in Chest Radiology?

Objective: While the coronavirus disease 2019 (COVID-19) pandemic was continuing at full speed, patients with Crimean-Congo hemorrhagic fever (CCHF), which is endemic in our region, apply to the emergency department simultaneously. The presence of computed tomography (CT) lesions suggesting COVID-19 in some CCHF patients has brought to our mind the question of whether there is CCHF lung involvement even though respiratory symptoms are not at the forefront. Methods: In this study, the findings of chest CT, demographic data and clinical symptoms of cases who had thorax tomography scan with suspicion of COVID-19 in the emergency department in the spring and summer of 2020 and were diagnosed with CCHF as a result of the evaluation and followed up in our clinic were compared with the findings of COVID-19 cases that were hospitalized and treated in the same period. Results: Seventy-seven COVID-19 and 25 CCHF cases were included in the study. Myalgia, headache, diarrhea, nausea and vomiting were significantly higher in CCHF patients ( p<0.05). Cough was significantly more common in COVID-19 patients ( p=0.034). Ground-glass opacity (GGO) was the most common tomography finding in CCHF, and cases without lung involvement were significantly higher (p=0.001). GGO, consolidation, vascularization, atelectasis band, reverse halo, air-bubble, nodule were significantly high in COVID-19 patients. Conclusion: During the epidemic period, no pathological finding was found in thoracic CT in most of the CCHF cases, and the presence of involvement in the lung tomography in cases with similar clinical and laboratory findings should primarily suggest the diagnosis of COVID-19.

A Rare Presentation of Leptospirosis: Dysarthria and Guillain-Barré Syndrome.

Leptospirosis can present with severe cases such as polymyositis, peripheral neuropathy, and rarely, Guillain-Barré Syndrome (GBS). This paper reports a case who presented with dysarthria and GBS. A female patient presented with complaints of weakness, dizziness, diarrhea, and dysarthric. Her assessments included muscle strength globally 4/5 and deep tendon reflexes as hypoactive. An electromyographic examination was performed with the increase of weakness in the lower extremities, which indicated findings compatible with GBS. Antibodies against Leptospira biflexa serovar Patoc 1 at 1/400 titer were detected in the microscopic agglutination test (MAT). Neurological involvement in leptospirosis cases can range from meningoencephalitis to GBS.

Intravoxel incoherent motion parameters in the evaluation of chronic hepatitis B virus-induced hepatic injury: fibrosis and capillarity changes.

OBJECTIVE: To evaluate the diagnostic efficacy of intravoxel incoherent motion (IVIM) parameters in hepatitis B virus (HBV)-induced hepatic fibrosis using different calculation methods and to investigate histopathologic origins. MATERIALS AND METHODS: Liver biopsies from 37 prospectively recruited chronic hepatitis B patients were obtained. Twelve b-value (0-1000 s/mm2) diffusion-weighted imaging (DWI) was performed with a 1.5 T scanner and was followed by blinded percutaneous liver biopsy. All biopsy specimens were evaluated with Ishak staging, and the microvascular density (MVD) was calculated. Patients were classified as having no/mild (F0-1), moderate (F2-3), or marked (F4-5) fibrosis. Pseudodiffusion (D*), the perfusion fraction (f), and the apparent diffusion coefficient (ADC) were calculated using all b-values, while true diffusion (D) was calculated using all b-values [D0-1000] and b-values greater than 200 s/mm2 [D200-1000]. Three concentric regions of interest (ROIs) (5, 10, and 20 mm) centered on the biopsy site were used. RESULTS: D* was correlated with the MVD (p = 0.015, Pearson's r = 0.415), but f was not (p = 0.119). D0-1000 was inversely correlated with Ishak stage (p = 0.000, Spearman's rs = - 0.685) and was significantly decreased in all the fibrosis groups; however, only the no/mild and marked fibrosis groups had significantly different D200-1000 values. A pairwise comparison of receiver operating characteristic (ROC) curves of D0-1000 and D200-1000 showed significant differences (p = 0.039). D* was the best at discriminating early fibrosis (AUC = 0.861), while the ADC best discriminated advanced fibrosis (AUC = 0.964). CONCLUSION: D* was correlated with the MVD and is a powerful parameter to discriminate early hepatic fibrosis. D significantly decreased with advanced fibrosis stage when using b-values less than 200 s/mm2 in calculations.

Disseminated Nocardia farcinica infection presenting as a paravertebral abscess in a patient with systemic lupus erythematosus.

Disseminated Nocardia infections occur particularly in immunosuppressed hosts and are most often due to Nocardia farcinica, Nocardia nova, and Nocardia cyriacigeorgica. Here, we report an unusual case of disseminated N. farcinica infection presenting as a paravertebral abscess in a patient with systemic lupus erythematosus.

Epidemiologic and clinical characteristics of HIV/AIDS patients in Turkey, where the prevalence is the lowest in the region.

The authors describe the epidemiologic and clinical characteristics of 97 human immunodeficiency virus (HIV)-infected patients, who were followed between 1993 and 2006. Seventy-two percent of the patients were male, and median age at diagnosis was 36 years (range, 13-71 years). The mean years of survival was 3, and maximum length of life after diagnosis was 9 years. The most common professions were truck drivers, workers, and housewives. Forty-six percent of the males had a history of working abroad. Heterosexual intercourse was the most common (84%) route of transmission. Seventy-four percent of the women acquired infection from their husbands. In Turkey, less educated or uneducated and poor men are the primary target of the HIV infection usually by sexual contact with foreign women. Considering the low education status of the patients, appropriate education programs should be developed to prevent the dissemination of HIV infection. Because a significant number of patients were diagnosed at very late stages, the physicians and other health care workers should be educated on the clinical pictures of HIV/AIDS.

The lack of Crimean-Congo hemorrhagic fever virus antibodies in healthcare workers in an endemic region.

We aimed to detect antibodies against Crimean-Congo hemorrhagic fever virus (CCHFV) in healthcare workers (HCWs) in an endemic region. The study was conducted in a tertiary care hospital that had cared for CCHFV infected patients in the period 2002-2003. The sera from the HCWs were collected one month after the last admitted hospital case (October 2003), and sent to the Pasteur Institute, Lyon, France to be studied for CCHF IgM and IgG by ELISA. The total number of HCWs included in the study was 75; the median age was 30, 68% of the subjects were female, and 83% of the HCWs were at risk of exposure to the body fluids of patients. Only one HCW from the group without risk of exposure was CCHF IgG positive. The adherence rate to universal precautions was high. In conclusion, a lack of CCHFV transmission from patients to HCWs was observed. This result could be related to the high rate of compliance to the universal precautions, which are sufficient to protect against CCHFV infection.

Measles, rubella, mumps, and varicella seroprevalence among health care workers in Turkey: is prevaccination screening cost-effective?

BACKGROUND: To investigate the immune status of health care workers (HCWs) against measles, rubella, mumps, and varicella zoster (MMRV) in Turkey and to define an appropriate vaccination program among HCWs. METHODS: Voluntary HCWs from a children's hospital and a general hospital were included in the study between March and May 2005. The specific IgG antibodies against MMRV viruses were screened by ELISA. RESULTS: Three hundred sixty-three HCWs participated in the study; 186 (51%) were physicians, 118 (33%) were nurses, 36 (10%) were housekeeping staff, and 23 (6%) were medical technicians. The proportion of HCWs who had antibodies against measles was 98.6%; rubella, 98.3%; mumps, 92.2%; and varicella, 98%. No association was found between the susceptibility to at least 1 of MMRV virus infections and gender, age, duration of work, profession, and department of work in analysis either among the whole study group, or each hospital. The positive predictive value for the history of varicella was 100%, whereas it was 92% for MMR. The cost of vaccination for varicella was significantly expensive without screening before vaccination. However, there was not much difference for MMR infections. CONCLUSION: A policy based on obtaining the history of varicella infection from the staff and then screening the ones with negative history and vaccination of only seronegative HCWs was found to be appropriate.

[Malaria in Turkey and 14 years of clinical experience]. / Turkiye'de sitma ve 14 yillik klinik deneyimimiz.

In this retrospective study, the epidemiologic and clinical characteristics of 105 adult malaria patients, who had been hospitalized between the period of 1992 and 2006 were evaluated. Nineteen percent of the patients were female, and the mean age was 28 +/- 10 years. Fifty percent of the patients acquired the infection in Southeastern Anatolia, while they were on military duty. The most common complaints were rigor (93%), fever (90%), sweating (90%), headache (76%), nausea (45%), and fatigue (38%). The most common physical examination findings were splenomegaly (86%) and hepatomegaly (62%). Anemia was detected in 23%, leukopenia in 47%, thrombocytopenia in 73%, two fold increase in ALT or AST enzyme levels in 32% of the patients. Plasmodium vivax was detected in 101 (96%) patients, whereas P. falciparum was detected in 4 patients (4%). Although the number of malaria cases in Turkey is declining in recent years, the febrile patients with a history of travel to the endemic regions should raise the suspicion of malaria.

HIV-1 Transmitted Drug Resistance Mutations in Newly Diagnosed Antiretroviral-Naive Patients in Turkey.

HIV-1 replication is rapid and highly error-prone. Transmission of a drug-resistant HIV-1 strain is possible and occurs within the HIV-1-infected population. In this study, we aimed to determine the prevalence of transmitted drug resistance mutations (TDRMs) in 1,306 newly diagnosed untreated HIV-1-infected patients from 21 cities across six regions of Turkey between 2010 and 2015. TDRMs were identified according to the criteria provided by the World Health Organization's 2009 list of surveillance drug resistance mutations. The HIV-1 TDRM prevalence was 10.1% (133/1,306) in Turkey. Primary drug resistance mutations (K65R, M184V) and thymidine analogue-associated mutations (TAMs) were evaluated together as nucleos(t)ide reverse transcriptase inhibitor (NRTI) mutations. NRTI TDRMs were found in 8.1% (107/1,306) of patients. However, TAMs were divided into three categories and M41L, L210W, and T215Y mutations were found for TAM1 in 97 (7.4%) patients, D67N, K70R, K219E/Q/N/R, T215F, and T215C/D/S mutations were detected for TAM2 in 52 (3.9%) patients, and M41L + K219N and M41L + T215C/D/S mutations were detected for the TAM1 + TAM2 profile in 22 (1.7%) patients, respectively. Nonnucleoside reverse transcriptase inhibitor-associated TDRMs were detected in 3.3% (44/1,306) of patients (L100I, K101E/P, K103N/S, V179F, Y188H/L/M, Y181I/C, and G190A/E/S) and TDRMs to protease inhibitors were detected in 2.3% (30/1,306) of patients (M46L, I50V, I54V, Q58E, L76V, V82A/C/L/T, N83D, I84V, and L90M). In conclusion, long-term and large-scale monitoring of regional levels of HIV-1 TDRMs informs treatment guidelines and provides feedback on the success of HIV-1 prevention and treatment efforts.

Characteristics of B. melitensis versus B. abortus bacteraemias.

OBJECTIVE: To determine the epidemiological and the clinical characteristics of bacteremic brucellosis. METHODS: A prospective study, performed in the First Infectious Diseases Clinic of Ankara Numune Education and Research Hospital. All the patients had positive culture result for Brucella spp. RESULTS: Fifty-four acute bacteremic brucellosis cases were included. The majority of patients (76%) were from rural Anatolia. Brucella melitensis serotypes were more common than Brucella abortus (83% versus 17%). Fever and arthralgia were the most common symptoms. The number of patients with back pain and arthralgia was higher in B. abortus infected group (p = 0.014 and p = 0.009). CONCLUSIONS: B. melitensis is the most common subtype of Brucella infection in Turkey. The infections with B. abortus spp. are not less severe than the infections with B. melitensis.

Crimean Congo hemorrhagic fever infection simulating acute appendicitis.

An unusual cause of acute abdominal pain simulating acute appendicitis is presented. The patient was admitted with complaints of fever, malaise, headache, nausea, vomiting, diarrhoea, and severe bleeding. Based on the clinical and epidemiological findings, a diagnosis of Crimean Congo hemorrhagic fever virus infection was suspected, and ribavirin therapy was started. While her clinical condition was improving, she experienced a sudden pain at her right lower quadrant of the abdomen. Explorative laparotomy revealed haemorrhage within the abdominal muscles. Her CCHF IgM was found to be positive.

[Two leptospirosis cases and review of the national literature]. / Iki leptospiroz olgusu ve yerli literatürün gözden geçirilmesi.

In this report, two cases of leptospirosis admitted to our clinic in the same periods, have been presented. The first patient was a 29 years old male farmer, and the other was a 44 years old male prisoner. Both of them were from Middle Anatolian Region with the similar clinical findings (subfebrile fever, gastrointestinal complaints, ichterus in sclera, leucocytosis, and increased levels of liver enzymes, urea and creatine). The diagnosis was based on the antibody positivities against Leptospira with microscopic agglutination test which performed in the Etlik Central Veterinary Control and Research Institute. The first case was positive for L. grippotyphosa, and the second was positive for L. australis serovar bratislava at the titers of 1/800. Both of the patients were given empirical antibiotic treatment (ceftriaxone 2 x 1 gr, and ampicillin-sulbactam 4 x 1 gr, respectively), and discharged with complete healing. These cases led us to review the other leptospirosis cases in our country.