Clinical and genomic evaluations of a persistent fatal SARS-CoV-2 infection in a goods syndrome patient: a case report.

The coronavirus disease of 2019 (COVID-19) resulted from an infection by severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) which is the main cause of acute respiratory distress syndrome (ARDS) in global population from 2019 on. It may contribute to higher rate of death among the patients with immunodeficiency based on recent reports. In addition, Good syndrome (GS) as a result of thymoma removal might cause in some long-lasting microbial infections. We described clinical aspects and viral mutations on a case of GS suffering from COVID-19. A 46-year-old man with fever, common respiratory disease symptoms and positive COVID-19 polymerase chain reaction (PCR) test, with the history of thymoma removal surgery was admitted to Masih Daneshvari Hospital, Tehran, Iran. Lung radiographs and oxygen saturation measurement disclosed considerable implication resulted in application of several anti-microbial medication. The delta variant (B.1.617.2 (21 J Clade)) was the strain isolated from the patient by sequencing methods done by the COVID-19 National Reference Laboratory (CNRL), Pasteur Institute of Iran, while the dominant strain circulated mostly among population was Omicron (B.1.1.529) at the time of sampling. Unfortunately, the patient had passed away a month later by sudden respiratory failure progressed in refractory septic shock. Despite the fact that opportunistic infections may lead the GS patients to a major health problematic condition, unusual persistent of infections such as non-dominant variant of SARS-Cov-2 could be observed through the disease timeline. Therefore, a fully screening of thymoma plus intra-host evolution monitoring of SARS-CoV-2 is highly recommended in immunocompromised patients.

High Prevalence of Azole-Resistant Aspergillus fumigatus Among Iranian Cystic Fibrosis Patients: Should We Be Concerned?

BACKGROUND: Cystic fibrosis (CF), an inherited autosomal recessive disorder, is linked with high morbidity and mortality rates due to bacteria, filamentous, yeast and black yeast-like fungi colonisation in the upper respiratory tract. Although Candida species are the most common fungi isolated from CF patients, azole-resistant Aspergillus fumigatus (ARAf) is a big concern for invasive aspergillosis. Notably, the exact prevalences of Aspergillus species and the prevalence of ARAf isolates among Iranian CF patients have yet to be previously reported and are unknown. We aimed to investigate the prevalence of ARAf isolates in CF patients among Iranian populations by focusing on molecular mechanisms of the mutations in the target gene. METHODS: The 1 year prospective study recovered 120 sputum samples from 103 CF patients. Of these, 55.1% (86/156) yielded Aspergillus species, screened for ARAf using plates containing itraconazole (4 mg/L) and voriconazole (1 mg/L). According to the CLSI-M38 guidelines, antifungal susceptibility testing was performed using the broth microdilution method. In all phenotypically resistant isolates, the target of azole agents, the cyp51A gene, was sequenced to detect any possible single nucleotide polymorphisms (SNP) mediating resistance. RESULTS: Of 120 samples, 101 (84.2%) were positive for filamentous fungi and yeast-like relatives, with 156 fungal isolates. The most common colonising fungi were Aspergillus species (55.1%, 86/156), followed by Candida species (39.8%, 62/156), Exophiala species (3.8%, 6/156) and Scedosporium species (1.3%, 2/156). Forty out of 86 (46.5%) were identified for section Fumigati, 36 (41.9%) for section Flavi, 6 (7%) for section Nigri and 4 (4.6%) for section Terrei. Fourteen out of 40 A. fumigatus isolates were phenotypically resistant. The overall proportion of ARAf in total fungal isolates was 9% (14/156). cyp51A gene analysis in resistant isolates revealed that 13 isolates harboured G448S, G432C, T289F, D255E, M220I, M172V, G138C, G54E and F46Y mutations and one isolate carried G448S, G432C, T289F, D255E, M220I, G138C, G54E and F46Y mutations. Additionally, this study detects two novel cyp51A single-nucleotide polymorphisms (I242V and D490E). CONCLUSIONS: This study first investigated ARAf isolates in Iranian CF patients. Due to a resistance rate of up to 9%, it is recommended that susceptibility testing of Aspergillus isolates from CF patients receiving antifungal treatment be a part of the routine diagnostic workup. However, extensive multicentre studies with a high volume of CF patients are highly warranted to determine the impact of ARAf on CF patients.

Clinical epidemiology of pulmonary aspergillosis in hospitalized patients and contribution of Cyp51A, Yap1, and Cdr1B mutations to voriconazole resistance in etiologic Aspergillus species.

Pulmonary aspergillosis is a life-threatening fungal infection with worldwide distribution. In the present study, clinical epidemiology of pulmonary aspergillosis and antifungal susceptibility of etiologic Aspergillus species were evaluated in one-hundred fifty patients with special focus on the frequency of voriconazole resistance. All the cases were confirmed by the clinical pictures, laboratory findings, and isolation of etiologic Aspergillus species which belonged to two major species, i.e., A. flavus and A. fumigatus. Seventeen isolates displayed voriconazole MIC greater than or equal to the epidemiological cutoff value. Expression of cyp51A, Cdr1B, and Yap1 genes was analyzed in voriconazole-intermediate/resistant isolates. In A. flavus, Cyp51A protein sequencing showed the substitutions T335A and D282E. In the Yap1 gene, A78C replacement led to Q26H amino acid substitution that was not reported previously in A. flavus resistant to voriconazole. No mutations associated with voriconazole resistance were found in the three genes of A. fumigatus. The expression of Yap1 was higher than that of two other genes in both A. flavus and A. fumigatus. Overall, voriconazole-resistant strains of both A. fumigatus and A. flavus demonstrated overexpression of Cdr1B, Cyp51A, and Yap1 genes compared to voriconazole-susceptible strains. Although there are still ambiguous points about the mechanisms of azole resistance, our results showed that mutations were not present in majority of resistant and intermediate isolates, while all of these isolates showed overexpression in all three genes studied. As a conclusion, it seems that the main reason of the emergence of mutation in voriconazole-resistant isolates of A. flavus and A. fumigatus is previous or prolonged exposure to azoles.

Extracorporeal membrane oxygenation and COVID-19: The causes of failure.

INTRODUCTION: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a therapeutic strategy for the coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). There are inconclusive data in this regard and causes of VV-ECMO failure are not yet understood well. CASE SERIES: Here, seven patients with COVID-19-induced ARDS who underwent VV-ECMO introduced and causes of VV-ECMO failure discussed. Medical records of seven COVID-19 patients treated with VV-ECMO were retrospectively evaluated to determine the clinical outcomes of VV-ECMO. Oxygenator failure occurred in four patients whom needed to oxygenator replacement. Successful VV-ECMO decannulation was done in three patients, however finally one patient survived. CONCLUSIONS: Hypercoagulability state and oxygenator failure were the most main etiologies for VV-ECMO failure in our study. All patients with COVID-19 undergoing VV-ECMO should be monitored for such problems and highly specialized healthcare team should monitor the patients during VV-ECMO.

Airway colonisation by Candida and Aspergillus species in Iranian cystic fibrosis patients.

Cystic fibrosis (CF) is associated with increased rates of morbidity and mortality due to fungal and bacterial colonisation of the airways or respiratory infections. The prevalence of fungi in Iranian CF population has been underestimated. Therefore, the current study was conducted to define the frequency of fungi in respiratory specimens obtained from Iranian CF patients based on conventional and molecular assays. Furthermore, in vitro antifungal susceptibility testing was performed on the obtained isolates according to the guidelines from the Clinical and Laboratory Standards Institute. A cohort of 42 CF patients, including 29 males and 13 females, were categorised according to the referenced diagnostic criteria. Candida albicans (n = 24, 80%), C. dubliniensis (n = 2, 6.6%), C. parapsilosis (n = 2, 6.6%), C. tropicalis (n = 1, 3.3%), C. glabrata (n = 1, 3.3%) and Meyerozyma caribbica (n = 1, 3.3%) were isolated from 73.8% of the CF patients. Aspergillus terreus (n = 3, 42.8%) was identified as the most common Aspergillus species, followed by A. fumigatus (n = 2, 28.5%), A. oryzae (n = 1, 14.2%) and A. flavus (n = 1, 14.2%). Bacterial and fungal co-colonisation was detected in 7 (16.6%) and 22 (52.3%) samples that were positive for Aspergillus and Candida species, respectively. However, Scedosporium species and Exophiala dermatitidis never were detected. In terms of geometric mean (GM) minimum inhibitory concentrations (MICs), posaconazole (0.018 µg/mL) and caspofungin (0.083 µg/mL) exhibited the highest antifungal activities against all Candida species. In addition, posaconazole exhibited the lowest MIC range (0.008-0.063 µg/mL) against all Aspergillus species, followed by caspofungin (0.016-0.125 µg/mL) and voriconazole (0.125-0.25 µg/mL). To conclude, it is essential to adopt a consistent method for the implementation of primary diagnosis and determination of treatment regimen for the CF patients. However, further studies are still needed to better define the epidemiology of fungal organisms in CF patients from the Middle East and the clinical significance of their isolation.

Side effects after COVID-19 vaccination: a comparison between the most common available vaccines in Iran.

Background and Objectives: Since the coronavirus disease 2019 (COVID-19) pandemic began, several vaccines have been manufactured to subside it. This study aimed to determine the prevalence of side effects after injecting common COVID-19 vaccines available in Iran. Materials and Methods: This cross-sectional study was accomplished on Shahid Beheshti University of Medical Sciences (Tehran, Iran) employees during January and September 2022. Eligible participants were selected based on the simple random method and interviewed about side effects after injecting COVID-19 vaccine. Results: The mean age of 656 participants was 38.03 ± 9.53 years, and 453 (69.1%) were female. The prevalence of post-vaccination side effects was higher after receiving the first dose (53.2%) than the second (35.9%) and third (49.4%) doses. Across all three vaccine doses, the overall proportion of side effects was higher following AstraZeneca than the others. The most common side effect after the first dose of the vaccine was myalgia (41.9%), followed by fever (36.6%), chills (31.6%), local reactions (27.0%), headache (25.5%), and sweating (21.6%). People experienced mainly myalgia (23.3%) and fever (20.3%) after injecting the second dose of the vaccine. Additionally, the participants had myalgia (37.2%), fever (30.8%), chills (29.2%), local reactions (26.0%), and headache (24.4%) after the third dose of the vaccine. Conclusion: AstraZeneca had a higher proportion of post-vaccination adverse effects than Sputnik V, Pastocovac, and Sinopharm. The most common side effects were flu-like syndrome and local reactions at the injection site. Furthermore, people rarely experienced life-threatening side effects. Thus, the available COVID-19 vaccines in Iran are safe.

Mixed etiology COVID-19 associated acute rhinosinusitis caused by two Aspergillus species.

INTRODUCTION: Acute invasive fungal rhino-sinusitis (AIFR) is a life-threatening infection that is mostly found in immunocompromised patients with serious morbidity and mortality. Recently, reports of AIFR have also emerged among SARS-CoV-2 infected patients. CASE PRESENTATION: A 50-year-old diabetic woman, previously diagnosed with COVID-19 pneumonia, was presented to the hospital with left facial pain on day 12 after discharge. Paranasal sinuses computed tomography was performed and according to the mucosal thickening in both maxillary sinuses and ethmoidal air cells, the patient underwent functional endoscopic sinus surgery (FESS) and necrosis were observed. The histopathologic examination revealed mycelium with septation suspected to Aspergillus and the culture was consistent with Aspergillus flavus and also Aspergillus niger . We reported a case of COVID-19 associated AIFR with two combined Aspergillus species from Iran. The patient received liposomal amphotericin B, which then switched to voriconazole combined with aggressive surgical debridement of necrotic tissues with a clinically favorable outcome. CONCLUSION: Mixed etiology AIFR can influence the outcome. However, further investigation is required upon this new threat.

Co-infection of Klebsiella pneumonia, Cytomegalovirus, Aspergillus and Zygomycete in a patient with SARS-CoV-2.

Co-infection between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other pathogens has become a serious threat. There are the reports of fungal, bacterial, and viral co-infections with SARS-CoV-2. We report the unusual case of concomitant aspergillosis, mucormycosis, cytomegalovirus pneumonia, and also klebsiella pneumoniae empyema as the complication of SARS-CoV-2.

Coinfection by Aspergillus and Mucoraceae Species in Two Cases of Acute Rhinosinusitis as a Complication of COVID-19.

Acute invasive fungal rhinosinusitis (AIFR) is a life-threatening infection often found in immunocompromised patients. In the COVID-19 era, reports of AIFR have emerged, with high mortality and morbidity rate. This paper presents two cases of COVID-19 associated AIFR with the combined proven fungal etiology of Aspergillus flavus and Rhizopus arrhizus in case 1 and Aspergillus fumigatus and Rhizopus arrhizus in case 2. Both patients received liposomal amphotericin B then posaconazole combined with aggressive surgical debridement of necrotic tissues with a favorable clinical outcome. Mixed etiology AIFR can influence the outcome; hence, further studies are required upon this new threat.

Effect of COVID-19 pandemic on incidence of mycobacterial diseases among suspected tuberculosis pulmonary patients in Tehran, Iran.

Background: Recent pandemic of coronavirus SARS-CoV-2 (COVID-19) caused limitations in the country's strategies to fight against mycobacterial infections. The aim of this study was to compare the suspected tuberculosis (TB) pulmonary patients before and during the COVID-19 pandemic (January 2018-December 2021) who were referred to the National Reference TB Laboratory (NRL TB), Tehran, Iran. The mycobacterial isolated strains were identified and compared with previous data. Methods: A total of 16,899 clinical samples collected from 7041 suspected pulmonary TB patients were received from 2018 to 2021. Primary isolation of Mycobacterium isolates was done on Löwenstein-Jensen medium. Then, the DNA was extracted from acid-fast bacillus culture-positive samples and identification was performed by IS6110, Hsp65, and 16S-23S rRNA genes using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and nested PCR methods. Results: A total of 11679 specimens (69.1%) from 4866 suspected TB patients were collected in 2018-2019 and 5220 specimens (30.8%; from 2175 patients) in 2020-2021. Out of 11679 specimens, 2046 samples that belong to 852 patients were infected with Mycobacterium tuberculosis, and the remaining were non-TB Mycobacterium (NTM) species (n = 244) isolated from 102 patients. The cultures for 12894 specimens were either negative (76.3%) or contaminated (845/16899; 5%). A comparison of the total number of patients who were referred for diagnosis and treatment (954/666 patients, P > 0.05) showed a 30.1% reduction during the COVID-19 pandemic. Although, with these low number of patients, the significant increases of NTM species (P < 0.05) among suspected TB pulmonary patients were observed. Besides, new species of NTM, for example, Mycobacterium peregrinum and Mycobacterium montefiorense, were detected. For the past 20 years, these two species were not reported from pulmonary patients in Iran. Conclusions: During the pandemic of COVID-19, the TB diagnosis network became irregular, as a consequence, many patients could not reach the treatment center, and this could increase the circulation of mycobacterial diseases (TB and NTM). The study shows the emergence of new opportunistic NTM species also.

Evaluation of Lymphocyte Subtypes in COVID-19 Patients.

Background: Although many aspects of the COVID-19 disease have not yet been clarified, dysregulation of the immune system may play a crucial role in the progression of the disease. In this study, the lymphocyte subsets were evaluated in patients with different severities of COVID-19. Materials and Methods: In this prospective study, the frequencies of peripheral lymphocyte subsets (CD3+, CD4+, and CD8+ T cells; CD19+ and CD20+ B cells; CD16+/CD56+ NK cells, and CD4+/CD25+/FOXP3+ regulatory T cells) were evaluated in 67 patients with confirmed COVID-19 on the first day of their admission. Results: The mean age of patients was 51.3 ± 14.8 years. Thirty-two patients (47.8%) were classified as severe cases, and 11 (16.4%) were categorized as critical. The frequencies of blood lymphocytes, CD3+ cells, CD25+FOXP3+ T cells, and absolute count of CD3+ T cells, CD25+FOXP3+ T cells, CD4+ T cells, CD8+ T cells, and CD16+56+ lymphocytes were lower in more severe cases compared to the milder patients. The percentages of lymphocytes, T cells, and NK cells were significantly lower in the deceased patients. (p= 0.002 and p= 0.042, p=0.006, respectively). Conclusion: Findings of this cohort study demonstrated that the frequencies of CD4+, CD8+, CD25+FOXP3+ T cells, and NK cells differed in the severe cases of COVID-19. Moreover, lower frequency of T cells and NK cells could be predictors of mortality in these patients.

National Research Institute of Tuberculosis and Lung Disease (NRITLD) Protocol for the Treatment of Patients with COVID-19.

More than a year after the onset of the coronavirus disease pandemic in 2019, the disease remains a major global health issue. During this time, health organizations worldwide have tried to provide integrated treatment guidelines to control coronavirus disease 2019 (COVID-19) at different levels. However, due to the novel nature of the disease and the emergence of new variants, medical teams' updating medical information and drug prescribing guidelines should be given special attention. This version is an updated instruction of the National Research Institute of Tuberculosis and Lung Disease (NRITLD) in collaboration with a group of specialists from Masih Daneshvari Hospital in Tehran, Iran, which is provided to update the information of caring clinicians for the treatment and care of COVID-19 hospitalized patients.

Case Report: COVID-19-associated Rhinosinusitis Mucormycosis Caused by Rhizopus arrhizus: A Rare but Potentially Fatal Infection Occurring After Treatment with Corticosteroids.

COVID-19 first emerged in Wuhan, China, in December 2019. Since that time, the frequency of bacterial and fungal coinfections has been continuously increasing. Although invasive pulmonary aspergillosis is being increasingly recognized in association with COVID-19, there is limited information regarding COVID-19-associated mucormycosis. We describe a 50-year-old woman with uncontrolled diabetes who received systemic corticosteroids and remdesevir during her admission for COVID-19. A few days after discharge, the patient was readmitted because of facial swelling and numbness, and a diagnosis of COVID-19-associated rhinosinusitis mucormycosis caused by Rhizopus arrhizus (formerly called Rhizopus oryzae) was confirmed with sequencing of the internal transcribed spacer region of the ribosomal DNA. This report aimed to address the importance of short-term follow-up for COVID-19 patients who have received systemic corticosteroids, particularly those with predisposing conditions, because early detection and prompt, aggressive treatment are essential for the management of invasive fungal infections.

Combined Therapy of Ciclosporin Plus Favipiravir in the Management of Patients with Severe COVID-19, not Responding to Dexamethasone: A non-Controlled Prospective Trial.

BACKGROUND: Regarding the COVID-19 pandemic, potential therapeutic agents are being evaluated almost every day. Ciclosporin, a calcineurin inhibitor, is characterized by beneficial antiviral and immunomodulatory effects. The present study aimed to evaluate the efficacy of ciclosporin in managing COVID-19. METHODS: This study was a prospective non-controlled clinical trial carried out on 20 patients. Confirmed COVID-19 patients received two doses of ciclosporin (10 mg/kg and 5 mg/kg injections) 24 h apart. Mortality rate and the lengths of intensive care unit (ICU) and hospital stays were assessed for all 20 patients. RESULTS: The mortality rate and the need for mechanical ventilation were calculated as 50%. The percentage of ICU admission was 70%. The lengths of ICU and hospital stays were 8.13 ± 6.81 and 14.25 ± 8.55 days, respectively. The levels of ferritin and white blood cells were significantly higher after injecting the second dose of ciclosporin. Seven patients (35%) had radiologically improved lungs after ciclosporin therapy. CONCLUSION: It seems that the protocol of two doses of ciclosporin in combination with favipiravir does not have favorable effects among COVID-19 patients that do not respond to dexamethasone. Controlled trials are needed to confirm the results.

Evaluating the effects of Intravenous Immunoglobulin (IVIg) on the management of severe COVID-19 cases: A randomized controlled trial.

BACKGROUND: The newly discovered coronavirus has turned into coronavirus disease 2019 (COVID-19) pandemic and it rages at an unprecedented rate. Considering the findings of previous studies on the use of Intravenous Immunoglobulin (IVIg) for treating severe H1N1 infection and the satisfying results for reducing viral load and mortality, this study aimed to investigate the potential usefulness of IVIg for the management of severe cases. METHODS: In this randomized controlled trial, 84 patients were included: 52 in the IVIg group and 32 in the control group. The intervention group received IVIg at a dose of 400 mg/kg, IV, daily for three days. Both groups received hydroxychloroquine, lopinavir/ritonavir and supportive care. The demographic data, mortality rate, the need for mechanical ventilation, length of stay in hospital and in Intensive Care Unit (ICU), and imaging findings were recorded and compared in terms of the mentioned factors. RESULTS: The mean time from admission to IVIg initiation was 3.84 ± 3.35 days. There was no significant difference between the two groups in terms of mortality rate (P-value = 0.8) and the need for mechanical ventilation (P-value = 0.39). The length of hospital stay was significantly lower for the control group than that of the intervention group (P-value = 0.003). There was a significant positive relationship between the time from hospital admission to IVIg initiation and the length of stay in the hospital and ICU among the survivors (P-value < 0.001 and =0.01, respectively). CONCLUSIONS: Our findings did not support the use of IVIg in combination with hydroxychloroquine and lopinavir/ritonavir in treatment of severe COVID-19 cases.

Combination therapy of IFNß1 with lopinavir-ritonavir, increases oxygenation, survival and discharging of sever COVID-19 infected inpatients.

Interferon Beta-1a (IFN-ß1-a), an immunomodulatory mediator with antiviral effects, has shown in vivo and in vitro activities especially on coronavirus including SARS-CoV-2. COVID-19 defined as the disease caused by infection with SARS-CoV-2. The virus has been illustrated inhibits the production of IFN-ß1-a from inflammatory cells. We conducted a retrospective study of all adult confirmed COVID-19 hospitalized patients who received combination of three doses of 12 million international units of IFN-ß1-a and Lopinavir 400 mg and Ritonavir 100 mg every 12 h (case group) for 14 days besides standard care and age- and sex- matched COVID-19 patients with receiving lopinavir/ritonavir (control group) at Masih Daneshvari Hospital as a designated hospital for COVID-19 between Feb 19 and Apr 30, 2020. Multivariate analysis was done to determine the impact of IFN-ß1-a on outcome and all-cause mortality. 152 cases in IFN-ß1-a group and 304 cases as control group were included. IFN-ß1-a group stayed at hospital longer and required noninvasive ventilation more than control group (13 vs. 6 days, p = 0.001) and (34% vs. 24%, p = 0.04), respectively. During treatment, 57 (12.5%) patients died. The death rate in case and control groups was 11% and 13% respectively. In multivariate analysis, not receiving IFN-ß1-a (HR 5.12, 95% CI: 2.77-9.45), comorbidity (HR 2.28, 95% CI: 1.13-4.60) and noninvasive ventilation (HR 2.77, 95% CI: 1.56-4.93) remained significantly associated with all-cause mortality. In this study, risk of death decreased by using IFN-ß1-a in COVID-19 patients. More clinical study will be necessary to measure efficacy of IFN-ß1-a in COVID-19 treatment.

No clinical benefit of high dose corticosteroid administration in patients with COVID-19: A preliminary report of a randomized clinical trial.

The aim of this study was to evaluate the clinical effects of dexamethasone administration in patients with mild to moderate acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). The study included 50 patients who were randomly assigned to the dexamethasone group or control group. Dexamethasone was administered at a dose of 20 mg/day from day 1-5 and then at 10 mg/day from day 6-10. The need for invasive mechanical ventilation, death rate, duration of clinical improvement, length of hospital stay, and radiological changes in the computed tomography scan were assessed. The results revealed that 92% and 96% of patients in the dexamethasone and control groups, respectively, required noninvasive ventilation (P = 0.500). Among them, 52% and 44% of patients in the dexamethasone and control groups, respectively, required invasive mechanical ventilation (P = 0.389). At the end of the study, 64% of patients in the dexamethasone group and 60% of patients in the control group died (P = 0.500); the remaining patients were discharged from the hospital during the 28-day follow-up period. The median length of hospital stay was 11 days in the dexamethasone group and 6 days in the control group (P = 0.036) and the median length of hospital stay was 7 days in the dexamethasone group and 3 days in the control group (P < 0.001). No significant differences were observed in the other outcomes. This study showed that corticosteroid administration had no clinical benefit in patients with COVID-19-induced mild to moderate ARDS.

Favipiravir Effects on the Control of Clinical Symptoms of Hospitalized COVID-19 Cases: An Experience with Iranian Formulated Dosage Form.

Coronavirus disease -19 (COVID-19) pandemic, caused by SARS-CoV-2, has gradually spread worldwide, becoming a major public health event. This situation requires designing a novel antiviral agent against the SARS-CoV-2; however, this is time-consuming and the use of repurposed medicines may be promising. One such medicine is favipiravir, primarily introduced as an anti-influenza agent in east world. The aim of this study was to evaluate the efficacy and safety of favipiravir in comparison with lopinavir-ritonavir in SARS-CoV-2 infection. In this randomized clinical trial, 62 patients were recruited. These patients had bilateral pulmonary infiltration with peripheral oxygen saturation lower than 93%. The median time from symptoms onset to intervention initiation was seven days. Favipiravir was not available in the Iranian pharmaceutical market, and it was decided to formulate it at the research laboratory of School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients received favipiravir tablet at a dose of 1600 mg orally twice a day for day one and then 600 mg orally twice a day for days 2 to 6. In the second group, the patients received lopinavir-ritonavir combination tablet at a dose of 200/50 mg twice a day for seven days. Fever, cough, and dyspnea were improved significantly in favipiravir group in comparison with lopinavir-ritonavir group on days four and five. Mortality rate and ICU stay in both groups were similar, and there was no significant difference in this regard (P = 0.463 and P = 0.286, respectively). Chest X-ray improvement also was not significantly different between the two groups. Adverse drug reactions occurred in both groups, and impaired liver enzymes were the most frequent adverse effect. In conclusion, early administration of oral favipiravir may reduce the duration of clinical signs and symptoms in patients with COVID-19 and hospitalization period. The mortality rate also should be investigated in future clinical trials.

Promising effects of tocilizumab in COVID-19: A non-controlled, prospective clinical trial.

BACKGROUND: The clinical presentation of SARS-CoV-2 infection ranges from mild symptoms to severe complications, including acute respiratory distress syndrome. In this syndrome, inflammatory cytokines are released after activation of the inflammatory cascade, with the predominant role of interleukin (IL)-6. The aim of this study was to evaluate the effects of tocilizumab, as an IL-6 antagonist, in patients with severe or critical SARS-CoV-2 infection. METHODS: In this prospective clinical trial, 76 patients with severe or critical SARS-CoV-2 infection were evaluated for eligibility, and ultimately, 42 patients were included. Tocilizumab was administered at a dose of 400 mg as a single dose via intravenous infusion. Primary outcomes included changes in oxygenation support, need for invasive mechanical ventilation, and death. Secondary outcomes included radiological changes in the lungs, IL-6 plasma levels, C-reactive protein levels, and adverse drug reactions. The data were analyzed using SPSS software. RESULTS: Of the 42 included patients, 20 (48%) patients presented the severe infection stage and 22 (52%) were in the critical stage. The median age of patients was 56 years, and the median IL-6 level was 28.55 pg/mL. After tocilizumab administration, only 6 patients (14%) required invasive ventilation. Additionally, 35 patients (83.33%) showed clinical improvement. By day 28, a total of 7 patients died (6 patients in the critical stage and 1 patient in the severe stage). Neurological adverse effects were observed in 3 patients. CONCLUSIONS: Based on the current results, tocilizumab may be a promising agent for patients with severe or critical SARS-CoV-2 infection, if promptly initiated during the severe stage.

Clinical Manifestations of Patients with Coronavirus Disease 2019 (COVID-19) in a Referral Center in Iran.

BACKGROUND: Following the recent epidemic of coronavirus disease 2019 (COVID-19) in Wuhan, China, a novel betacoronavirus was isolated from two patients in Iran on February 19, 2020. In this study, we aimed to determine the clinical manifestations and outcomes of the first confirmed cases of COVID-19 infection (n=127). MATERIALS AND METHODS: This prospective study was conducted on all COVID-19-suspected cases, admitted to Masih Daneshvari Hospital (a designated hospital for COVID-19), Tehran, Iran, since February 19, 2020. All patients were tested for COVID-19, using reverse transcription-polymerase chain reaction (RT-PCR) assay. Data of confirmed cases, including demographic characteristics, clinical features, and outcomes, were collected and compared between three groups of patients, requiring different types of admission (requiring ICU admission, admission to the general ward, and transfer to ICU). RESULTS: Of 412 suspected cases, with the mean age of 54.1 years (SD=13.4), 127 (31%) were positive for COVID-19. Following the patients' first visit to the clinic, 115 cases were admitted to the general ward, while ten patients required ICU admission. Due to clinical deterioration in the condition of 25 patients (out of 115 patients), ICU admission was essential. Based on the results, the baseline characteristics of the groups were similar. Patients requiring ICU admission were more likely to have multiorgan involvement (liver involvement, P<0.001; renal involvement, P<0.001; and cardiac involvement, P=0.02), low O2 saturation (P<0.001), and lymphopenia (P=0.05). During hospital admission, 21 (16.5%) patients died, while the rest (83.5%) were discharged and followed-up until March 26, 2020. Also, the survival rate of patients, who received immunoglobulin, was higher than other patients (60.87% vs. 39.13%). CONCLUSION: The mortality rate of COVID-19 patients was considerable in our study. Based on the present results, this infection can cause multiorgan damage. Therefore, intensive monitoring of these patients needs to be considered.