Assessment of Risk Factors and Clinical Outcomes in Hospitalized COVID-19 Patients with Candida spp. Co-infections: Species Distribution and Antifungal Susceptibility Patterns of Isolates.

INTRODUCTION: Fungal co-infections are considered an important complication in hospitalized patients with SARS-CoV-2 that can be attributed to disease aggravation, increased mortality, and poor outcomes. This study was conducted to determine the species distribution and antifungal susceptibility patterns of Candida isolates from hospitalized COVID-19 patients in Shiraz, Iran, in addition to associated risk factors and outcomes of co-infections with Candida species. MATERIALS AND METHODS: In this single-center study, a total of 106 hospitalized COVID-19 patients were evaluated for clinical characteristics and outcomes. Species identification was performed by ITS1-5.8S-ITS2 gene sequencing. Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, amphotericin B, and nystatin was determined according to the M27-A3/S4 CLSI protocol. RESULTS: Candida species were recovered from 48% (51/106) of hospitalized COVID-19 patients. Statistical analysis showed that patients who had heart failure, bacterial co-infection, and were receiving empirical antifungal therapy had a higher risk of developing Candida co-infection. In total, 71 Candida isolates were recovered, of which C. albicans (69%) was the most prevalent isolate. The majority of the Candida isolates were susceptible to all classes of tested antifungal drugs. DISCUSSION: Our results elucidate a high rate of Candida co-infections among hospitalized COVID-19 patients. Comorbidities such as heart failure, HTN, COPD, bacterial infections as well as therapeutic interventions including catheterization, mechanical ventilation, and ICU admission increased the risk of Candida spp. isolation from the bloodstream, respiratory tract and urine samples, which led to a higher in-hospital mortality rate. Additionally, obtained data clarified that empirical antifungal therapy was not as successful as anticipated.

COVID-19 versus applied infection control policies in a Major Transplant Center in Iran.

BACKGROUND: Since Shiraz Transplant Center is one of the major transplant centers in Iran and the Middle East, this study was conducted to evaluate outcomes of the applied policies on COVID-19 detection and management. METHODS: During 4 months from March to June 2020, patient's data diagnosed with the impression of COVID-19 were extracted and evaluated based on demographic and clinical features, along with the length of hospital stay and expenses. RESULTS: Our data demonstrated that a total of 190 individuals, with a median age of 58, were diagnosed with COVID-19 during the mentioned period. Among these, 21 patients had a positive PCR test and 56 patients had clinical symptoms in favor of COVID-19. Also, 113 (59%) patients were classified as mild based on clinical evidence and were treated on an outpatient basis. Furthermore, 81 out of 450 cases (18%) of the healthcare workers at our center had either PCR of clinical features in favor of COVID-19. The mortality rate of our study was 11% and diabetes mellitus, hypertension were considered risk factors for obtaining COVID-19 infection. The direct cost of treatment and management of patients with COVID-19 amounted to 2,067,730,919 IRR, which considering the 77 patients admitted to Gary Zone per capita direct cost of treatment each patient was 26,853,648 IRR. CONCLUSION: We demonstrated that the COVID-19 pandemic had a noticeable influence on our transplant center in aspects of delaying surgery and increased hospital costs and burden. However, by implanting proper protocols, we were able to was able to provide early detection for COVID-19 and apply necessary treatment and prevention protocols to safeguard the patients under its coverage, especially immunocompromised patients.

Drug-related Problems in Solid-Organ Transplant Recipients Hospitalized for COVID-19: An Experience of a Referral Tertiary Center in Iran.

Background: Transplanted patients receiving immunosuppressive agents are at a higher risk of Coronavirus-disease-2019 (COVID-19), and their polypharmacy state makes the choice of treatment challenging. This study aimed to assess the drug-related problems (DRP) and clinical pharmacists' interventions to manage transplanted patients and candidates for transplantation with COVID-19. Methods: This cross-sectional study was conducted in the COVID-19 intensive care unit of Shiraz Organ Transplantation Center (Iran), from March 2020 to April 2021. Patients were admitted to the COVID-19 intensive care unit based on clinical symptoms or positive polymerase chain reaction (PCR) tests. The clinical pharmacist reviewed all medications and physicians' orders on a daily basis and evaluated DRPs in accordance with the pharmaceutical care network of Europe (PCNE) classification (V 8.01). The treatment team was informed of the DRPs, and the acceptance or rejection of the intervention was also documented. Data were analyzed using SPSS (Version 25.0). In order to determine the proportion and determinants of drug-related problems, descriptive statistics and logistic regression were applied, respectively. Results: A clinical pharmacist reviewed 631 individuals with 11770 medication orders, and 639 DRPs were found in 69% of them with an average of 1.01±1 per patient. The most commonly reported DRPs were treatment efficacy issues followed by adverse drug reactions (ADRs). A total of 982 interventions were provided at prescriber, patient, and drug levels, of which 801 were accepted, and 659 (82.27%) were fully implemented. Conclusion: There have been considerable drug-related issues in managing transplanted patients with COVID-19. DRPs are more common in people with polypharmacy, more than three comorbidities, and hydroxychloroquine regimens.

Bacterial and fungal co-infections with SARS-CoV-2 in solid organ recipients: a retrospective study.

BACKGROUND: SARS-CoV-2, a novel corona virus, has caused clusters of fatal pneumonia worldwide. Immune compromised patients are among the high risk groups with poor prognosis of the disease. The presence of bacterial or fungal co-infections with SARS-CoV-2 is associated with increased mortality. METHODS: The electronic data of the liver and kidney recipients, hospitalized in COVID-19 intensive care unit in an 8-month period in 2020 were retrospectively assessed. The documented bacterial or fungal infections alongside with outcome and risk factors were recorded and analyzed by binary logistic regression model and multivariate analyses. RESULTS: Sixty-Six liver and kidney recipients with positive RT-PCR for SARS-CoV-2 were included this study. Twenty one percent of the patients had at least one episode of co-infection during their COVID-19 course. Bacterial and fungal co-infections contributed to a significantly higher mortality. Urine and sputum were the most common sites of pathogen isolation (45.45% and 36.36%; respectively). The majority of infections were caused by vancomycin- resistant Enterococci (30%). Escherichia coli stood in the next position with 23.3%. Prior hospitalization and high doses of corticosteroids were associated with co-infections (p < 0.001 and p = 0.02; respectively.) CONCLUSIONS: Bacterial and fungal co-infections with COVID-19 are more prevalent in solid organ recipients compared to the general population. Prior hospitalizations and use of broad-spectrum antimicrobial agents lead to emergence of multi-drug resistant pathogens in this susceptible patient population. Early detection and treatment of co-infections as well as antibiotic stewardship is recommended in solid organ recipients.

Evaluation of the therapeutic regimen in COVID-19 in transplant patients: where do immunomodulatory and antivirals stand?

BACKGROUND: The management of COVID-19 in organ transplant recipients is among the most imperative, yet less discussed, issues based on their immunocompromised status along with their vast post-transplant medication regimens. No conclusive study has been published to evaluate proper anti-viral and immunomodulator medications effect in treating COVID-19 patients to this date. METHOD: This retrospective study was conducted in Shiraz Transplant Hospital, Iran from March 2020 to May 2021 and included COVID-19 diagnosed patients based on SARS-CoV-2 RT-PCR positive test who had been hospitalized for at least 48 h before enrolling in the study. Clinical and demographic information of patients, along with their treatment course and the medication used were evaluated and analyzed using multiple regression analysis. RESULTS: A total of 245 patients with a mean age of 49.59 years were included with a mortality rate of 8.16%. The administration of Remdesivir as an anti-viral drug (P value < 0.001) and Tocilizumab as an immunomodulator drug (P value < 0.001) could reduce the hospitalization period in the hospital and the intensive care unit, as well as the mortality rates significantly. Meanwhile, the patients treated with Lopinavir/Ritonavir experienced a lower chance of survival (OR < 1, P value = 0.04). No significant difference was observed between various therapeutic regimens in clinical complications such as bacterial coinfections, cardiovascular and gastrointestinal adverse reactions, and liver or kidney dysfunctions. CONCLUSION: The administration of Remdesivir as an anti-viral and Tocilizumab as an immunomodulatory drug in solid-organ transplant recipients could be promising treatments of choice to manage COVID-19.

Pharmacotherapeutic approach toward urological medications and vaccination during COVID-19: a narrative review.

One year after the prevalence of the novel coronavirus pandemic, some aspects of the physiopathology, treatment and progression of coronavirus 2019 disease (COVID-19) have remained unknown. Since no comprehensive study on the use of urological medications in patients with COVID-19 has been carried out, this narrative review aimed to focus on clinically important issues about the treatment of COVID-19 and urologic medications regarding efficacy, modifications, side effects and interactions in different urologic diseases. In this review, we provide information about the pharmacotherapeutic approach toward urologic medications in patients with COVID-19 infection. This study provides an overview of medications in benign prostatic hyperplasia, prostate cancer, impotence and sexual dysfunction, urolithiasis, kidney transplantation and hypertension as the most frequent diseases in which the patients are on long-term medications. Also, the effect of urologic drugs on the efficacy of vaccination is briefly discussed.

Administration of COVID-19 vaccines in immunocompromised patients.

Since the beginning of vaccination programs against COVID-19 in different countries, several populations such as patients with specific immunological conditions have been considered as the priorities for immunization. In this regard, patients with autoimmune diseases or those receiving immunosuppressive agents and anti-cancer therapies, need special attention. However, no confirmed data is presently available regarding COVID-19 vaccines in these populations due to exclusion from the conducted clinical trials. Given the probable suppression or over-activation of the immune system in such patients, reaching a consensus for their vaccination is critical, besides gathering data and conducting trials, which could probably clarify this matter in the future. In this review, besides a brief on the available COVID-19 vaccines, considerations and available knowledge about administering similar vaccines in patients with cancer, hematopoietic stem cell transplantation, solid organ transplantation, multiple sclerosis (MS), inflammatory bowel disease (IBD), and rheumatologic and dermatologic autoimmune disorders are summarized to help in decision making. As discussed, live-attenuated viruses, which should be avoided in these groups, are not employed in the present COVID-19 vaccines. Thus, the main concern regarding efficacy could be met using a potent COVID-19 vaccine. Moreover, the vaccination timing for maximum efficacy could be decided according to the patient's condition, indicated medications, and the guides provided here. Post-vaccination monitoring is also advised to ensure an adequate immune response. Further studies in this area are urgently warranted.

Coronavirus Disease 2019 (COVID-19) and Transplantation: Pharmacotherapeutic Management of Immunosuppression Regimen.

The 2019 novel coronavirus disease (COVID-19) was first detected in Wuhan, Hubei Province, China, in late 2019. Since then, COVID-19 has spread to more than 200 countries in the world, and a global pandemic has been declared by the World Health Organization (WHO). At present, no vaccines or therapeutic regimens with proven efficacy are available for the management of COVID-19. Hydroxychloroquine/chloroquine, lopinavir/ritonavir, ribavirin, interferons, umifenovir, remdesivir, and interleukin antagonists, such as tocilizumab, have been recommended as potential treatment options in COVID-19. Transplant patients receiving immunosuppressant medications are at the highest risk of severe illness from COVID-19. At the same time, with regard to receiving polypharmacy and immunosuppressants, treatment options should be chosen with more attention in this population. Considering drug-drug interactions and adverse effects of medications used for the treatment of COVID-19, such as QT prolongation, the dose reduction of some immunosuppressants or avoidance is recommended in transplant recipients with COVID-19. Thus, this narrative review describes clinically important considerations about the treatment of COVID-19 and immunosuppressive regimens regarding modifications, side effects, and interactions in adult kidney or liver allograft recipients.

Pediatric liver and kidney transplantation in the era of COVID-19: a follow-up study from a tertiary referral center in Iran.

BACKGROUND: We aimed to evaluate the impact of COVID-19 pandemic on pediatric transplant outcomes and determine whether to continue pediatric transplant activity or not, and how policies intended our center has been effective in preventing COVID-19 among organ transplant recipients. METHODS: We conducted a single-center, retrospective, cohort study of hospitalized pediatrics after organ transplantation at Shiraz transplant center since March to August 2020. All liver and kidney transplanted children were included the study and their laboratory and clinical related COVID-19 characteristics were followed up till 3 months after transplantation during hospitalization period and then weekly by the transplant committee. RESULTS: Fifty-one patients underwent transplantation including 11 kidney and 40 liver recipients. The mean age of the pediatric cases was 6.72 ± 5.47 years. A total of 11 patients died due to post-transplant complications, while none of the patients presented any sign or symptoms in favor of COVID-19 in the hospital course after transplantation. Six transplants including 2 kidney and 4 liver were canceled when positive PCR tests were detected in their donors before the surgery. In the 3 months of follow up, two patients presented with symptoms including high grade fever, malaise, rhinorrhea, and GI symptoms. Both patients had two negative PCR, and no radiologic or laboratory results regarding COVID-19 were also detected. One had positive influenza PCR, while the second one had a positive serologic test for EBV; CT, computed tomography CONCLUSION: Transplant programs could continue their activities during the COVID-19 pandemic with specific case selection, accurate screening methods and following protective protocols.