Radiologic Findings of COVID-19 Associated Mucormycosis (CAM) from India

Background. The unique feature of the second wave of the COVID -19 pandemic in India has been the alarming surge of acute invasive fungal infection among COVID -19 patients. The increased incidence of rhino-orbito-cerebral mucormycosis is a matter of concern, as this fulminant infection has high morbidity and mortality. Hence, it is imperative to understand it's imaging features, for early diagnosis, staging and treatment. Methods. We systematically reviewed 32 COVID-19 cases with imaging diagnosis of acute invasive fungal rhino-sinusitis or rhino-orbital-cerebral disease between March to May 2021. These patients underwent contrast MRI of the paranasal sinus, orbit and brain. Contrast enhanced CT chest and paranasal sinuses were done as needed. Results. The age group ranged between 30 to 71 yrs with male preponderance. The most common predisposing factors were intravenous steroid therapy and supplemental oxygen. All cases were confirmed by fungal culture and most common was Mucor. The rhino-orbito-cerebral mucormycosis was staged as below In our study we found that the most common site in the nasal cavity was the middle turbinate /meatus and the earliest sign was non-enhancing / "black" turbinate. Premaxillary and retroantral fat necrosis was the earliest sign of soft tissue invasion. Spread via the sphenopalatine foramen and pterygopalatine fossa was more common than bony erosions. Orbital cellulitis and optic neuritis were the most common among stage 3 cases. Of patients with CNS involvement, the most common were cavernous sinus thrombosis and trigeminal neuritis. Two patients with pulmonary mucormycosis showed large necrotic cavitary lesions, giving the characteristic "bird's nest" appearance. Conclusion. The mortality rate was 20% in our study. In our short term follow up, 30 % of recovered patients had relapse on imaging due to incomplete clearance and partial antifungal treatment. High clinical suspicion and low imaging threshold are vital for early Mucormycosis detection in COVID-19 patients. Familiarity with early imaging signs is critical to prevent associated morbidity /mortality. Axial CT chest image in lung window shows necrotic right upper lobe cavity with internal septations and debris on a background of surrounding COVID-19 changes.

Head to Toe Imaging of Complications and Sequelae of COVID- 19 and COVID-19 Vaccination

Background. COVID 19 is associated with a hypercoagulable state with cytokine storm syndrome and thrombocytopenia leading to complications across various systems. COVID-19 infection, its treatment, resultant immunosuppression, and pre-existing comorbidities have made patients vulnerable to secondary infections Methods. We systematically reviewed COVID-19 cases between Jan to May 2021 for pulmonary and extrapulmonary complications. Patients with recent COVID-19 vaccination and neurological symptoms were also included. Results. Neurological complications: Neurological complications include ischemic and haemorrhagic strokes. Other complications are encephalopathy, encephalitis, Guillain-Barré syndrome, acute hemorrhagic necrotizing encephalopathy. Demyelination and radiculopathies are seen as post vaccination complications. Mucormycosis: Unprecedented high rate of invasive fungal sinusitis in association with COVID -19 is reported from the Indian subcontinent. This has a propensity for intra orbital and intracranial extension. COVID -19 associated coagulopathy: COVID -19 is a pro-inflammatory hypercoagulable state. Pulmonary thromboembolism, deep venous thrombosis and catheter related thrombosis are well documented. Cardiac complications: Cardiac manifestations include Myocardial Injury with non-obstructed coronary arteries (MINOCA), myocarditis, myocardial ischemia, cardiomyopathy. Pulmonary complications and sequelae of COVID -19: Progression of lung injury to ARDS during the initial phase and fibrosis of parenchyma in the recovery phase. Spontaneous pneumomediastinum, pneumatoceles and pneumothorax and secondary infections are identified in our study. COVID- 19 associated gastrointestinal complications: Patients evaluated for renal colic, pancreatitis, cholecystitis showed, ground glass opacities or subpleural bands in typical Covid-19 distribution. COVID-19 may lead of acute kidney and bowel injury due to arterial thrombosis. COVID - 19 associated myonecrosis: Ischemia of the small caliber vessels may result in myonecrosis. Conclusion. Awareness of these unusual manifestations will facilitate an early diagnosis, improve management and help reduce morbidity and mortality.

CURE ID as a Tool for Curating and Analyzing Drugs Used in COVID-19 Clinical Trials

Background. CURE ID is an internet-based data repository (https://cure.ncats. io/explore) developed collaboratively by FDA and NCATS/NIH. It is designed to capture real-world clinical outcome data to advance drug repurposing and to inform future clinical trials for infectious diseases with high unmet medical need. It also serves as a repository of clinical trials automatically pulled from https://www.clinicaltrials.gov into the CURE ID platform, where they were then manually curated, with the intention of keeping the infectious diseases community updated on the various clinical trials underway. The current study is a descriptive analysis of various therapeutics in clinical trials against COVID-19 on the CURE ID platform. Methods. Using clinicaltrials.gov we selected those trials addressing therapeutics for COVID-19 and reviewed the drugs used, the current status of the trials, and the phases of development. Results. As of May 2021, we identified 2,154 clinical trials and 933 drugs from clinicaltrials.gov that met the inclusion criteria. Hydroxychloroquine (n=251) was the most commonly investigated agent, followed by convalescent plasma (n=147), azithromycin (n=98), ivermectin (n=68), mesenchymal Stem Cells (n=63), tocilizumab (n=58), remdesivir (n=53) and favipiravir (n=51). At the time of our analysis, the majority (45%) of the clinical trials were in the recruiting phase, 12% were in the active phase, and 13% of the studies were completed. The majority (31%) of trials were in phase two, followed by phase three (21%) and phase one (10%). The vast majority of the agents were repurposed (92%), while only 8% of the agents were new molecular entities. Remdesivir was the only drug approved for marketing for treatment of certain patients with COVID-19 at the time of our analysis. Conclusion. Several repurposed and novel drugs are being investigated to treat COVID-19 in clinical trials. CURE ID provides a broad view of the various drugs being researched and serves to keep the scientific community informed. Such a platform may help prevent duplication of efforts and help the scientific community with more coordinated research efforts and larger platform trials that can robustly answer scientific questions during a pandemic.

Comparative pathology, molecular pathogenicity, immunological features, and genetic characterization of three highly pathogenic human coronaviruses (MERS-CoV, SARS-CoV, and SARS-CoV-2).

The last two decades have witnessed the emergence of three deadly coronaviruses (CoVs) in humans: severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are still no reliable and efficient therapeutics to manage the devastating consequences of these CoVs. Of these, SARS-CoV-2, the cause of the currently ongoing coronavirus disease 2019 (COVID-19) pandemic, has posed great global health concerns. The COVID-19 pandemic has resulted in an unprecedented crisis with devastating socio-economic and health impacts worldwide. This highlights the fact that CoVs continue to evolve and have the genetic flexibility to become highly pathogenic in humans and other mammals. SARS-CoV-2 carries a high genetic homology to the previously identified CoV (SARS-CoV), and the immunological and pathogenic characteristics of SARS-CoV-2, SARS-CoV, and MERS contain key similarities and differences that can guide therapy and management. This review presents salient and updated information on comparative pathology, molecular pathogenicity, immunological features, and genetic characterization of SARS-CoV, MERS-CoV, and SARS-CoV-2; this can help in the design of more effective vaccines and therapeutics for countering these pathogenic CoVs.

Immunopathogenesis and immunobiology of SARS-CoV-2

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), in a very short span of thirteen months has taken a considerable toll on humanity, resulting in over 3 million deaths with more than 150 million confirmed cases as on May 1, 2021. In the scarcity of a potential antiviral and protective vaccine, COVID-19 has posed high public health concerns, panic, and challenges to limit the spread of this pandemic virus. Only recently have a few vaccine candidates been developed, and vaccination programs have started in some countries. Multiple clinical presentations of COVID-19, animal spillover, cross-species jumping, zoonotic concerns, and emergence of virus variants have altogether created havoc during this ongoing pandemic. Several bodies of research are continuously working to elucidate the exact molecular mechanisms of the pathogenesis. To develop a prospective antiviral therapy/vaccine for SARSCoV-2, it is quite essential to gain insight into the immunobiology and molecular virology of SARS-CoV-2. A thorough literature search was conducted up to 28th February 2021 in the PubMed and other databases for the articles describing the immunopathology and immune response of SARS-CoV-2 infection, which were critically evaluated and used to compile this article to present an overall update. Some of the information was drawn from studies on previous MERS and SARS viruses. Innate as well as adaptive immunity responses are elicited by exposure to SARS-CoV-2. SARS-CoV-2 establishes a successful infection by escaping the host immunity as well as over activating the innate immune mechanisms that result in severe disease outcomes, including cytokine storm. This review summarizes the immunopathology and molecular immune mechanisms elicited during SARS-CoV-2 infection, and their similarities with MERS-CoV and SARS-CoV.

Airborne transmission of SARS-CoV-2 is the dominant route of transmission: droplets and aerosols

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic worldwide. On a daily basis the number of deaths associated with COVID-19 is rapidly increasing. The main transmission route of SARS-CoV-2 is through the air (airborne transmission). This review details the airborne transmission of SARS-CoV-2, the aerodynamics, and different modes of transmission (e.g. droplets, droplet nuclei, and aerosol particles). SARS-CoV-2 can be transmitted by an infected person during activities such as expiration, coughing, sneezing, and talking. During such activities and some medical procedures, aerosols and droplets contaminated with SARS-CoV-2 particles are formed. Depending on their sizes and the environmental conditions, such particles stay viable in the air for varying time periods and can cause infection in a susceptible host. Very few studies have been conducted to establish the mechanism or the aerodynamics of virus-loaded particles and droplets in causing infection. In this review we discuss the various forms in which SARS-CoV-2 virus particles can be transmitted in air and cause infections.