Proven pulmonary aspergillosis in a COVID-19 patient: A case report.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) has become a significant clinical challenge in healthcare settings all over the world. Critically ill COVID-19 patients with acute respiratory distress syndrome may be at increased risk of co-infection with pulmonary aspergillosis. This study aimed to describe a clinical case of proven pulmonary aspergillosis caused by Aspergillus tubingensis in a 59-year-old man with a history of hospitalization due to COVID-19 infection. CASE REPORT: The Covid-19 infection was confirmed by positive nasopharyngeal polymerase chain reaction. He had a cavitary lesion measured 20 mm in diameter with intracavitary soft tissue density in the left lung in the first chest computerized tomography scan. After 25 days, he showed two cavitary lesions in both lungs which raised suspicion of fungal infection; hence, the patient underwent a trans-thoracic biopsy of the cavitary lesion. The direct examination and culture of the biopsy material revealed Aspergillus species. To confirm the Aspergillus species identification, the beta-tubulin region was sequenced. The patient was treated with oral voriconazole. CONCLUSION: This report underlined the importance of early diagnosis and management of invasive fungal infections in severe COVID-19 patients.

Inflawell® improves neutrophil-to-lymphocyte ratio and shortens hospitalization in patients with moderate COVID-19, in a randomized double-blind placebo-controlled clinical trial.

AIMS: COVID-19 is a significant global threat to public health. Despite the availability of vaccines and anti-viral drugs, there is an urgent need for alternative treatments to help prevent and/or manage COVID-19 symptoms and the underlying dysregulated immune response. We hypothesized that administration of Inflawell® syrup, a Boswellia extract formulation enriched for boswellic acids (BAs), can reduce the excessive or persistent inflammation and thereby prevent disease progression. BAs are medicinally activated triterpenoids found in the resins of Boswellia spp., and possess an immense therapeutic potential due to their anti-inflammatory and immunoregulatory activities. We investigated the effect of Inflawell® syrup, on moderate COVID-19 patients along with the current standard of care treatment. METHODS: A randomized placebo-controlled double-blind clinical trial was conducted, following definitive confirmation of COVID-19. Forty-seven hospitalized patients with moderate COVID-19 were enrolled and received either the Inflawell® syrup or placebo. Clinical symptoms and markers of inflammation were evaluated at baseline and completion of the trial. RESULTS: Our clinical trial revealed an increase in the percentage of oxygen saturation level in patients that received the BAs compared to placebo (P < 0.0001). In addition, the average duration of hospitalization was significantly shorter in the BAs group compared with the placebo group (P < 0.04). Concomitantly, some improvement in the clinical symptoms including cough, dyspnea, myalgia, headache, and olfactory and gustatory dysfunction were detected in the BAs group. Hematologic findings showed a significant decrease in the percentage of neutrophils (P < 0.006) and neutrophil-to-lymphocyte ratio (NLR) levels (P < 0.003), associated with a significant increase in the percentage of lymphocytes in the BAs group compared with the placebo (P < 0.002). Additionally, a significant decrease in CRP, LDH, IL - 6 and TNF - α levels was detected in the BAs group. Following the intervention, fewer patients in the BAs group were PCR-positive for COVID-19 compared to placebo, though not statistically significant. CONCLUSION: Overall, the treatment with Inflawell® resulted in shorter hospital stay, alleviation of COVID-19 clinical symptoms and decline in the level of pro-inflammatory cytokines. TRIAL REGISTRATION: The trial has been registered in  https://www.irct.ir  with unique identifier: IRCT20170315033086N10 ( https://en.irct.ir/trial/51631 ). IRCT is a primary registry in the WHO registry network ( https://www.who.int/clinical-trials-registry-platform/network/primary-registries ).

Serious events following COVID‐19 vaccination with ChAdOx1 nCoV‐19 vaccine (Vaxzevria): A short case series from Iran

In 2020, the SARS‐COV‐2 disease (COVID‐19) imposed huge challenges on the health, economic, and political systems, and by the end of the year, hope had been born with the release of COVID‐19 vaccines aimed at bringing the pandemic to an end. However, the COVID‐19 vaccination programs have sparked several concerns and ongoing debates over safety issues. Here, we presented three cases of patients with serious adverse events, encephalopathy, vaccine‐induced thrombotic thrombocytopenia, and leukocytoclastic vasculitis, after receiving the ChAdOx1 nCoV‐19 vaccine. Therefore, it is critical to investigate and report the occurrence of adverse reactions following vaccination, particularly serious ones, as it contributes to the growing body of research and assists clinicians in better diagnosing and managing them. Despite the crucial role of COVID‐19 vaccination in controlling the pandemic, occurring of the severe adverse effects following inoculation is also inevitable and should be considered

Serious events following COVID-19 vaccination with ChAdOx1 nCoV-19 vaccine (Vaxzevria): A short case series from Iran.

In 2020, the SARS-COV-2 disease (COVID-19) imposed huge challenges on the health, economic, and political systems, and by the end of the year, hope had been born with the release of COVID-19 vaccines aimed at bringing the pandemic to an end. However, the COVID-19 vaccination programs have sparked several concerns and ongoing debates over safety issues. Here, we presented three cases of patients with serious adverse events, encephalopathy, vaccine-induced thrombotic thrombocytopenia, and leukocytoclastic vasculitis, after receiving the ChAdOx1 nCoV-19 vaccine. Therefore, it is critical to investigate and report the occurrence of adverse reactions following vaccination, particularly serious ones, as it contributes to the growing body of research and assists clinicians in better diagnosing and managing them.

Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spread rapidly all over the world in late 2019 and caused critical illness and death in some infected patients. This study aimed at examining several laboratory factors, especially inflammatory and immunological mediators, to identify severity and mortality associated biomarkers. Ninety-three hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) were classified based on disease severity. The levels of biochemical, hematological, immunological, and inflammatory mediators were assessed, and their association with severity and mortality were evaluated. Hospitalized patients were mostly men (77.4%) with an average (standard deviation) age of 59.14 (14.81) years. The mortality rate was significantly higher in critical patients (85.7%). Increased serum levels of blood sugar, urea, creatinine, uric acid, phosphorus, total bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-oxaloacetic transaminase, lactic dehydrogenase, C-reactive protein, ferritin, and procalcitonin were significantly prevalent (p=0.002, p<0.001, p<0.001, p=0.014, p=0.047, p=0.003, p<0.001, p<0.001, p<0.001, p<0.001, P<0.001, and p<0.001, respectively) in COVID-19 patients. Decreased red blood cell, hemoglobin, and hematocrit were significantly prevalent among COVID-19 patients than healthy control subjects (p<0.001 for all). Troponin-I, interleukin-6, neutrophil/lymphocyte ratio (NLR), procalcitonin, and D-dimer showed a significant association with the mortality of patients with specificity and sensitivity more than 60%. Age, sex, underlying diseases, blood oxygen pressure, complete blood count along with C-reactive protein, lactic dehydrogenase, procalcitonin, D-dimer, and interleukin-6 evaluation help to predict the severity and required management for COVID-19 patients. Further investigations are highly recommended in a larger cohort study for validation of the present findings.

Proven Aspergillus flavus pulmonary aspergillosis in a COVID-19 patient: A case report and review of the literature.

Severe COVID-19 patients complicated with aspergillosis are increasingly reported. We present a histopathological proven case of fatal COVID-19-associated pulmonary aspergillosis (CAPA), due to Aspergillus flavus. This report and existing published literature indicate diagnostic challenges and poor outcomes of CAPA in ICU patients.

Clinical Characteristics and Outcomes of 905 COVID-19 Patients Admitted to Imam Khomeini Hospital Complex in the Capital City of Tehran, Iran.

BACKGROUND: We studied the clinical characteristics and outcomes of 905 hospitalized coronavirus disease 2019 (COVID-19) patients admitted to Imam Khomeini Hospital Complex (IKHC), Tehran, Iran. METHODS: COVID-19 patients were recruited based on clinical symptoms and patterns of computed tomography (CT) imaging between February 20 and March 19. All patients were tested for the presence of COVID-19 RNA. The Poisson regression model estimated the incidence rate ratio (IRR) for different parameters. RESULTS: The average age (± standard deviation) was 56.9 (±15.7) years and 61.77% were male. The most common symptoms were fever (93.59%), dry cough (79.78%), and dyspnea (75.69%). Only 43.76% of patients were positive for the RT-PCR COVID-19 test. Prevalence of lymphopenia was 42.9% and more than 90% had elevated lactate dehydrogenase (LDH) or C-reactive protein (CRP). About 11% were severe cases, and 13.7% died in the hospital. The median length of stay (LOS) was 3 days. We found higher risks of mortality in patients who were older than 70 years (IRR = 11.77, 95% CI 3.63-38.18), underwent mechanical ventilation (IRR = 7.36, 95% CI 5.06-10.7), were admitted to the intensive care unit (ICU) (IRR = 5.47, 95% CI 4.00-8.38), tested positive on the COVID-19 test (IRR = 2.80, 95% CI 1.64-3.55), and reported a history of comorbidity (IRR = 1.76, 95% CI 1.07-2.89) compared to their corresponding reference groups. Hydroxychloroquine therapy was not associated with mortality in our study. CONCLUSION: Older age, experiencing a severe form of the disease, and having a comorbidity were the most important prognostic factors for COVID-19 infection. Larger studies are needed to perform further subgroup analyses and verify high-risk groups.

Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial.

INTRODUCTION: There are no determined treatment agents for severe COVID-19. It is suggested that methylprednisolone, as an immunosuppressive treatment, can reduce the inflammation of the respiratory system in COVID-19 patients. METHODS: We conducted a single-blind, randomised controlled clinical trial involving severe hospitalised patients with confirmed COVID-19 at the early pulmonary phase of the illness in Iran. The patients were randomly allocated in a 1:1 ratio by the block randomisation method to receive standard care with methylprednisolone pulse (intravenous injection, 250 mg·day-1 for 3 days) or standard care alone. The study end-point was the time of clinical improvement or death, whichever came first. Primary and safety analysis was done in the intention-to-treat (ITT) population. RESULTS: 68 eligible patients underwent randomisation (34 patients in each group) from April 20, 2020 to June 20, 2020. In the standard care group, six patients received corticosteroids by the attending physician before the treatment and were excluded from the overall analysis. The percentage of improved patients was higher in the methylprednisolone group than in the standard care group (94.1% versus 57.1%) and the mortality rate was significantly lower in the methylprednisolone group (5.9% versus 42.9%; p<0.001). We demonstrated that patients in the methylprednisolone group had a significantly increased survival time compared with patients in the standard care group (log-rank test: p<0.001; hazard ratio 0.293, 95% CI 0.154-0.556). Two patients (5.8%) in the methylprednisolone group and two patients (7.1%) in the standard care group showed severe adverse events between initiation of treatment and the end of the study. CONCLUSIONS: Our results suggest that methylprednisolone pulse could be an efficient therapeutic agent for hospitalised severe COVID-19 patients at the pulmonary phase.

Oropharyngeal candidiasis in hospitalised COVID-19 patients from Iran: Species identification and antifungal susceptibility pattern.

BACKGROUND: Emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. Apparently, the novel coronavirus (SARS-CoV-2) is armed by special abilities to spread and dysregulate the immune mechanisms. The likelihood of oropharyngeal candidiasis (OPC) development in COVID-19 patients with a list of attributable risk factors for oral infections has not yet been investigated. OBJECTIVES: We here aim to investigate the prevalence, causative agents and antifungal susceptibility pattern of OPC in Iranian COVID-19 patients. PATIENTS AND METHODS: A total of 53 hospitalised COVID-19 patients with OPC were studied. Relevant clinical data were mined. Strain identification was performed by 21-plex PCR and sequencing of the internal transcribed spacer region (ITS1-5.8S-ITS2). Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, amphotericin B, caspofungin, micafungin and anidulafungin was performed according to the CLSI broth dilution method. RESULTS: In 53 COVID-19 patients with OPC, cardiovascular diseases (52.83%) and diabetes (37.7%) were the principal underlying conditions. The most common risk factor was lymphopaenia (71%). In total, 65 Candida isolates causing OPC were recovered. C albicans (70.7%) was the most common, followed by C glabrata (10.7%), C dubliniensis (9.2%), C parapsilosis sensu stricto (4.6%), C tropicalis (3%) and Pichia kudriavzevii (=C krusei, 1.5%). Majority of the Candida isolates were susceptible to all three classes of antifungal drugs. CONCLUSION: Our data clarified some concerns regarding the occurrence of OPC in Iranian COVID-19 patients. Further studies should be conducted to design an appropriate prophylaxis programme and improve management of OPC in critically ill COVID-19 patients.

Twelve Lessons on Hospital Leadership during COVID-19 Pandemic.

Coronavirus pandemic has been announced by World Health Organization Director General on March 11th, 2020. Imam Khomeini Hospital Complex, affiliated to Tehran University of Medical Sciences, was one the first referral hospitals in the capital city of Tehran, I.R.Iran that entered the crisis and started a serious battle with the disease. The hospital had to change many routine operations to cope with the situation and during this journey, we used published leadership principles and reached to some new experiences. As this is probably the most severe health-related crisis in Iran in the past 100 years, we gathered our lessons learned in the first fifty days of epidemic from the leadership point of view to share those with all colleagues worldwide. We know that leadership is of pivotal role in such a massive crisis and focused leadership experiences can help health care providers to manage the crisis while we are in the middle of it.

Fighting COVID-19: What Are the Available Options?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus, and its infection, coronavirus disease 2019 (COVID-19), have quickly become a worldwide threat. It is essential for clinicians to learn about this pandemic to manage patients. Among different aspects of the condition, is the treatment of this disease. Unfortunately, currently there is no effective treatment option that can be supported by evidence based medicine. This review analyzes information from literature on treatments.