Potential therapeutic applications of extracellular vesicles in the immunopathogenesis of COVID-19.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which has emerged as a global health crisis. Recently, more than 50 different types of potential COVID-19 vaccines have been developed to elicit a strong immune response against SARS-CoV-2. However, genetic mutations give rise to the new variants of SARS-CoV-2 which is highly associated with the reduced effectiveness of COVID-19 vaccines. There is still no efficient antiviral agent to specifically target the SARS-CoV-2 infection and treatment of COVID-19. Therefore, understanding the molecular mechanisms underlying the pathogenesis of SARS-CoV-2 may contribute to discovering a novel potential therapeutic approach to the management of COVID-19. Recently, extracellular vesicle (EV)-based therapeutic strategies have received great attention on account of their potential benefits in the administration of viral diseases. EVs are extracellular vesicles containing specific biomolecules which play an important role in cell-to-cell communications. It has been revealed that EVs are involved in the pathogenesis of different inflammatory diseases such as cancer and viral infections. EVs are released from virus-infected cells which could mediate the interaction of infected and uninfected host cells. Hence, these extracellular nanoparticles have been considered a novel approach for drug delivery to mediate the treatment of a wide range of diseases including, COVID-19. EVs are considered a cell-free therapeutic strategy that could ameliorate the cytokine storm and its complications in COVID-19 patients. Furthermore, EV-based cargo delivery such as immunomodulatory agents in combination with antiviral drugs may have therapeutic benefits in patients with SARS-CoV-2 infection. In this review, we will highlight the potential of EVs as a therapeutic candidate in the diagnosis and treatment of COVID-19. Also, we will discuss the future perspectives regarding the beneficial effects of Evs in the development of COVID-19 vaccines.

Iranian patients co-infected with COVID-19 and mucormycosis: the most common predisposing factor, clinical outcomes, laboratory markers and diagnosis, and drug therapies.

BACKGROUND: The newly emerged pandemic of coronavirus disease-2019 (COVID-19) is the world's main health challenge because infected patients become vulnerable to a variety of opportunistic diseases. OBJECTIVE: This study aimed to assess clinical outcomes, diagnosis, utilized drug therapies, and ongoing COVID-19 practices in Iranian cases co-infected with COVID-19 and mucormycosis. PARTICIPANTS AND METHODS: A case-series analysis was conducted in the presence of 10 patients with COVID-19 and mucormycosis co-infection (two men and eight women; mean age of 48.8 years) from March to October 2020. Demographic variables, signs/symptoms, and comorbidities of all patients were recorded. COVID-19 was confirmed with reverse transcription polymerase chain reaction (RT-PCR) nasopharyngeal swab tests and high-resolution computed tomography (HR-CT)_ scans. RESULTS: All patients had a positive RT-PCR for SARS-CoV-2. Eight patients had a history of diabetes, while three of them exhibited a hypertension history. Remarkable laboratory findings were elevated fasting blood sugar in 6 cases and anaemia in four patients. A rhino-orbital-cerebral of mucormycosis in all patients was detected based on HR-CT scans and otorhinolaryngological or ophthalmological examinations. Neurological disorders including facial, trigeminal, optic, and oculomotor nerve involvement resulted in paraesthesia, pain, ptosis, no light perception, blurred vision, and papilledema in five cases. Maxillary and ethmoid sinuses were the most common sites of involvement. CONCLUSION: Vulnerable COVID-19 patients with comorbidities, any facial involvements, or treated by excessive doses of glucocorticoids and antibiotics should undergo precise examinations during the appearance of early signs and hospitalization to diagnose and treat mucormycosis using the standard care and antifungal treatments.

"Pulmonary target sign" as a diagnostic feature in chest computed tomography of COVID-19.

BACKGROUND: In chest computed tomography (CT) scan, bilateral peripheral multifocal ground-glass opacities, linear opacities, reversed halo sign, and crazy-paving pattern are suggestive for coronavirus disease 2019 (COVID-19) in clinically suspicious cases, but they are not specific for the diagnosis, as other viral pneumonias, like influenza and some viral pneumonia may show similar imaging findings. AIM: To find a specific imaging feature of the disease would be a welcome guide in diagnosis and management of challenging cases. METHODS: Chest CT imaging findings of 650 patients admitted to a university Hospital in Tehran, Iran between January 2020 and July 2020 with confirmed COVID-19 infection by RT-PCR were reviewed by two expert radiologists. In addition to common non-specific imaging findings of COVID-19 pneumonia, radiologic characteristics of "pulmonary target sign" (PTS) were assessed. PTS is defined as a circular appearance of non-involved pulmonary parenchyma, which encompass a central hyperdense dot surrounded by ground-glass or alveolar opacities. RESULTS: PTS were presented in 32 cases (frequency 4.9%). The location of the lesions in 31 of the 32 cases (96.8%) was peripheral, while 4 of the 31 cases had lesions both peripherally and centrally. In 25 cases, the lesions were located near the pleural surface and considered pleural based and half of the lesions (at least one lesion) were in the lower segments and lobes of the lungs. 22 cases had multiple lesions with a > 68% frequency. More than 87% of cases had an adjacent bronchovascular bundle. Ground-glass opacities were detectable adjacent or close to the lesions in 30 cases (93%) and only in 7 cases (21%) was consolidation adjacent to the lesions. CONCLUSION: Although it is not frequent in COVID-19, familiarity with this feature may help radiologists and physicians distinguish the disease from other viral and non-infectious pneumonias in challenging cases.

The Primary Outcomes and Epidemiological and Clinical Features of Coronavirus Disease 2019 (COVID-19) in Iran.

AIM: We aimed to describe the epidemiological and clinical characteristics of Iranian patients with COVID-19. METHODS: In this single-center and retrospective study, patients with confirmed COVID-19 infections were enrolled. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with outcomes. RESULTS: Of 179 patients with confirmed COVID-19 infection, 12 remained hospitalized at the end of the study and 167 were included in the final analysis. Of these, 153 (91.6%) were discharged and 14 (8.38%) died in hospital. Approximately half (50.9%) of patients suffered from a comorbidity, with diabetes or coronary heart disease being the most common in 20 patients. The most common symptoms on admission were fever, dyspnea, and cough. The mean durations from first symptoms to hospital admission was 8.64 ± 4.14 days, whereas the mean hospitalization time to discharge or death was 5.19 ± 2.42 and 4.35 ± 2.70 days, respectively. There was a significantly higher age in non-survivor patients compared with survivor patients. Multivariate regression showed increasing odds ratio (OR) of in-hospital death associated with respiratory rates >20 breaths/min (OR: 5.14, 95% CI: 1.19-22.15, p = 0.028) and blood urea nitrogen (BUN) >19 mg/dL (OR: 4.54, 95% CI: 1.30-15.85, p = 0.017) on admission. In addition, higher respiratory rate was associated with continuous fever (OR: 4.08, 95% CI: 1.18-14.08, p = 0.026) and other clinical symptoms (OR: 3.52, 95% CI: 1.05-11.87, p = 0.04). CONCLUSION: The potential risk factors including high respiratory rate and BUN levels could help to identify COVID-19 patients with poor prognosis at an early stage in the Iranian population.

Ozone therapy for the treatment of COVID-19 pneumonia: A scoping review.

Severe forms of COVID-19 can evolve into pneumonia, featured by acute respiratory failure due to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In viral diseases, the replication of viruses is seemingly stimulated by an imbalance between pro-oxidant and antioxidant activity as well as by the deprivation of antioxidant mechanisms. In COVID-19 pneumonia, oxidative stress also appears to be highly detrimental to lung tissues. Although inhaling ozone (O3) gas has been shown to be toxic to the lungs, recent evidence suggests that its administration via appropriate routes and at small doses can paradoxically induce an adaptive reaction capable of decreasing the endogenous oxidative stress. Ozone therapy is recommended to counter the disruptive effects of severe COVID-19 on lung tissues, especially if administered in early stages of the disease, thereby preventing the progression to ARDS.

COVID-19 in rheumatoid arthritis cases: an Iranian referral center experience.

Coronavirus infections, known as COVID-19, can induce a fatal respiratory system infection and also affect other organs, such as the kidney and heart. The mortality rate has been estimated between 1 and 5% in previous reports; however, the mortality and morbidity can be higher in patients with the immune-deficiency condition. Rheumatoid arthritis (RA) is one of the most rheumatoid disorders, and it is important to report their clinical and paraclinical data when affected with COVID-19. Evidence about their laboratory and radiologic findings is limited. In this case series, 10 cases of chronic and approved rheumatoid arthritis (RA) affected by COVID-19 are presented. Only 40% had dry cough, but myalgia and weakness as the general first presentation of infections was reported in most cases (80%). Gastrointestinal symptoms, including nausea/vomiting, diarrhea, anorexia, and abdominal pain, were reported in 50% of individuals. In blood cell count, 30% of cases had thrombocytopenia, and ESR in all cases was positive. Abnormal CRP and elevated LDH were seen in 90% of cases. In HRCT assessment, all cases had an abnormal parenchymal pattern, and 90% of cases presented the usual pattern of COVID-19 (bilateral multifocal GGO/consolidation). Although it is a limited report, these findings are helpful for comparison of clinical and paraclinical cases in RA cases with normal cases.

Convalescent plasma therapy in a pregnant COVID-19 patient with a dramatic clinical and imaging response: A case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel very contagious infection which was designated a pandemic in all countries of the world in April 2020. Its presentation varies from mild to severe infection, but the majority of infected patients have mild manifestations. Many therapeutic choices have been suggested to treat the infection, but none are fully effective. CASE SUMMARY: Herein we present a 26-year-old woman with a twin pregnancy at 36 wk and one day gestation with confirmed COVID-19 who responded dramatically to convalescent plasma therapy (CPT) and Favipiravir. CONCLUSION: Although this case report shows the efficacy of CPT in addition to usual medications used for COVID-19, there are many questions that need to be answered regarding dosage, para-clinical efficacy, side effects and combination therapy.