Diminution of STING Expression in the Blood of Patients with Severe or Critical COVID-19 Pneumonia.

INTRODUCTION: Cytokine storm and critical COVID-19 pneumonia are caused in at least 10% of patients by inborn errors of or auto-Abs to type I IFNs. The pathogenesis of life-threatening COVID-19 pneumonia in other patients remains unknown. METHODS: This study was conducted at Masih Daneshvari Hospital, Tehran, Iran. In the period of study, 75 confirmed cases of COVID-19 with presentations ranging from mild upper respiratory tract infection to lower respiratory tract infection, including moderate, severe, and critical disease, were recruited. Expression of STING mRNA was measured in peripheral blood mononuclear cells (PBMCs) and compared between patients with different severity and outcome. RESULTS: There was a significant negative correlation between age and STING expression level (p value = 0.010). Patients with "severe to critical" illness had a 20-fold lower STING expression level compared to the "mild to moderate" group (p value = 0.001). Also, the results showed lower expressions of STING in the patients admitted to the ICU (p value = 0.015). Patients who finally died had lower expression of STING at the time of sampling (p value = 0.041). CONCLUSION: STING mRNA expression in PBMCs was significantly lower in older COVID-19 cases, the patients with more severe illness, who needed intensive care, and who eventually died.

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.

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.

Fatal invasive pulmonary aspergillosis in an immunocompetent patient with COVID-19 due to Aspergillus terreus: A case study.

Case reports of CAPA emerged. In most of the reports, the predominant species is Aspergillus fumigatus. Uncommon species are less reported. Due to poor clinical outcome with Aspergillus terreus, the increasing reports with this agent require attention.

Diffuse alveolar damage and thrombotic microangiopathy are the main histopathological findings in lung tissue biopsy samples of COVID-19 patients.

BACKGROUND: Since the outbreak of the novel coronavirus disease-2019 (COVID-19) in December 2019, limited studies have investigated the histopathologic findings of patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). MATERIAL AND METHODS: This study was conducted on 31 deceased patients who were hospitalized for COVID-19 in a tertiary hospital in Tehran, Iran. A total of 52 postmortem tissue biopsy samples were obtained from the lungs and liver of decedents. Clinical characteristics, laboratory data, and microscopic features were evaluated. Reverse transcription polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 was performed on specimens obtained from nasopharyngeal swabs and tissue biopsies. RESULTS: The median age of deceased patients was 66 years (range, 30-87 years) and 25 decedents (81 %) were male. The average interval from symptom onset to death was 13 days (range, 6-34 days). On histopathologic examination of the lung specimens, diffuse alveolar damage and thrombotic microangiopathy were the most common findings (80 % and 60 %, respectively). Liver specimens mainly showed macrovesicular steatosis, portal lymphoplasmacytic inflammation and passive congestion. No definitive viral inclusions were observed in any of the specimens. In addition, 92 % of lung tissue samples tested positive for SARS-CoV-2 by RT-PCR. CONCLUSIONS: Further studies are needed to investigate whether SARS-CoV-2 causes direct cytopathic changes in various organs of the human body.

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.