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.

Emerging coronavirus disease COVID-19, a pandemic public health emergency with animal linkages: current status update

After the appearance of first cases of pneumonia of unknown origin in the Wuhan city, China, during late 2019, the disease progressed fast. Its cause was identified as a novel coronavirus, named provisionally 2019-nCoV. Subsequently, an official name was given as SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus-2 by the International Committee on Taxonomy of Viruses ICTV study group. The World Health Organization WHO named the Coronavirus disease-2019 as COVID-19. The epidemics of COVID-2019 have been recorded over 113 countries/territories/areas apart from China and filched more than 4,292 humans, affecting severely around 1,18,326 cases in a short span. The status of COVID-2019 emergency revised by the WHO within 42 days from Public Health International Emergency January 30, 2020 to a pandemic March 11, 2020. Nonetheless, the case fatality rate CFR of the current epidemic is on the rise between 2-4%, relatively is lower than the previous SARS-CoV 2002/2003 and MERS-CoV 2012 outbreaks. Even though investigations are on its way, the researchers across the globe have assumptions of animal-origin of current SARS-CoV-2. A recent case report provides evidence of mild COVID-2019 infection in a pet dog that acquired COVID-2019 infection from his owner in Hong Kong. The news on travellers associated spread across the globe have also put many countries on alert with the cancellation of tourist visa to all affected countries and postponement of events where international visits were required. A few diagnostic approaches, including quantitative and differential real-time polymerase chain reaction assays, have been recommended for the screening of the individuals at risk. In the absence of any selective vaccine against SARS-CoV-2, re-purposed drugs are advocated in many studies. This article discourse the current worldwide situation of COVID-2019 with information on virus, epidemiology, host, the role of animals, effective diagnosis, therapeutics, preventive and control approaches making people aware on the disease outcomes.

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.

Modulation of host epigenome by coronavirus infections and developing treatment modalities for COVID-19 beyond genetics.

The recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) outbreak has resulted in coronavirus disease 2019 (COVID-19) pandemic worldwide, affecting millions of lives. Although vaccines are presently made available, and vaccination drive is in progress to immunize a larger population; still the risk of SARS-CoV-2 infection and related mortality is persistent amid threats of the third wave of the ongoing pandemic. In the scenario of unavailability of robust and efficient treatment modalities, it becomes essential to understand the mechanism of action of the virus and deeply study the molecular mechanisms (both at the virus level and the host level) underlying the infection processes. Recent studies have shown that coronaviruses (CoVs) cause-specific epigenetic changes in the host cells to create a conducive microenvironment for replicating, assembling, and spreading. Epigenetic mechanisms can contribute to various aspects of the SARS-CoV-2 multiplication cycle, like expressing cytokine genes, viral receptor ACE2, and implicating different histone modifications. For SARS-CoV-2 infection, viral proteins are physically associated with various host proteins resulting in numerous interactions between epigenetic enzymes (i.e., histone deacetylases, bromodomain-containing proteins). The involvement of epigenetic mechanisms in the virus life cycle and the host immune responses to control infection result in epigenetic factors recognized as emerging prognostic COVID-19 biomarkers and epigenetic modulators as robust therapeutic targets to curb COVID-19. Therefore, this narrative review aimed to summarize and discuss the various epigenetic mechanisms that control gene expression and how these mechanisms are altered in the host cells during coronavirus infection. We also discuss the opportunities to exploit these epigenetic changes as therapeutic targets for SARS-CoV-2 infection. Epigenetic alterations and regulation play a pivotal role at various levels of coronavirus infection: entry, replication/transcription, and the process of maturation of viral proteins. Coronaviruses modulate the host epigenome to escape the host immune mechanisms. Therefore, host epigenetic alterations induced by CoVs can be considered to develop targeted therapies for COVID-19.

Importance of bats in wildlife: not just carriers of pandemic SARS-CoV-2 and other viruses. (Special Issue: Coronaviruses and COVID-19- Past, Present, and Future.)

Bats are the only flying mammals that carry multiple pathogens, such as the SARS-CoV-2. As a consequent of fear of the zoonotic origin of SARS-CoV-2, there is an adverse reaction in multiple countries against these animals. Bats contribute with arthropod control and pollination, among other positive roles of these animals.

Comparison of various diagnostic techniques used to identify the presence of anti-SARS-CoV-2 immunoglobulin g

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a potentially lethal pathogen recently found to be responsible for the pandemic coronavirus disease 2019 (COVID-19). At present PCR testing remains the standard method of diagnosing COVID-19 patients. Recently, testing for SARS-CoV-2 immunoglobulin was identified as a promising method of diagnosing COVID-19 and assessing an individual's exposure to the virus. In the current study, four different techniques-CLIA, ELISA, ECLIA, and rapid testing-were used to assess the IgG antibody response in 20 patients following COVID-19 exposure. The data obtained using the CLIA and ELISA techniques illustrated that 90 percent of COVID-19 patients produced the SARS-COV-2 IgG antibody. Processing samples using the ECLIA method showed that these antibodies were present in 80 percent of all patients;however, the rapid testing technique showed that only 70 percent of patients were able to generate an immune response. The CLIA and ELISA techniques seemed to be more sensitive in terms of detecting SARS-COV-2 IgG, as they revealed that a high percentage of COVID-19 patients developed the IgG antibody. Conducting further research on the ongoing pandemic COVID-19, particularly studying antibody testing, will be valuable for diagnosing and monitoring patients.

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.

Emerging Coronavirus Disease (COVID-19), a pandemic public health emergency with animal linkages: Current status update

After the appearance of first cases of 'pneumonia of unknown origin' in the Wuhan city, China, during late 2019, the disease progressed fast. Its cause was identified as a novel coronavirus, named provisionally 2019-nCoV. Subsequently, an official name was given as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) by the International Committee on Taxonomy of Viruses (ICTV) study group. The World Health Organization (WHO) named the Coronavirus disease-2019 as COVID-19. The epidemics of COVID-2019 have been recorded over 113 countries/territories/areas apart from China and filched more than 4,292 humans, affecting severely around 1,18,326 cases in a short span. The status of COVID-2019 emergency revised by the WHO within 42 days from Public Health International Emergency (January 30, 2020) to a pandemic (March 11, 2020). Nonetheless, the case fatality rate (CFR) of the current epidemic is on the rise (between 2-4%), relatively is lower than the previous SARS-CoV (2002/2003) and MERS-CoV (2012) outbreaks. Even though investigations are on its way, the researchers across the globe have assumptions of animal-origin of current SARS-CoV-2. A recent case report provides evidence of mild COVID-2019 infection in a pet dog that acquired COVID-2019 infection from his owner in Hong Kong. The news on travellers associated spread across the globe have also put many countries on alert with the cancellation of tourist visa to all affected countries and postponement of events where international visits were required. A few diagnostic approaches, including quantitative and differential real-time polymerase chain reaction assays, have been recommended for the screening of the individuals at risk. In the absence of any selective vaccine against SARS-CoV-2, re-purposed drugs are advocated in many studies. This article discourse the current worldwide situation of COVID-2019 with information on virus, epidemiology, host, the role of animals, effective diagnosis, therapeutics, preventive and control approaches making people aware on the disease outcomes.

Predictors of COVID-19 severity: a systematic review and meta-analysis

Background: The unpredictability of the progression of coronavirus disease 2019 (COVID-19) may be attributed to the low precision of the tools used to predict the prognosis of this disease. Objective: To identify the predictors associated with poor clinical outcomes in patients with COVID-19. Methods: Relevant articles from PubMed, Embase, Cochrane, and Web of Science were searched and extracted as of April 5, 2020. Data of interest were collected and evaluated for their compatibility for the meta-analysis. Cumulative calculations to determine the correlation and effect estimates were performed using the Z test. Results: In total, 19 papers recording 1,934 mild and 1,644 severe cases of COVID-19 were included. Based on the initial evaluation, 62 potential risk factors were identified for the meta-analysis. Several comorbidities, including chronic respiratory disease, cardiovascular disease, diabetes mellitus, and hypertension were observed more frequent among patients with severe COVID-19 than with the mild ones. Compared to the mild form, severe COVID-19 was associated with symptoms such as dyspnea, anorexia, fatigue, increased respiratory rate, and high systolic blood pressure. Lower levels of lymphocytes and hemoglobin;elevated levels of leukocytes, aspartate aminotransferase, alanine aminotransferase, blood creatinine, blood urea nitrogen, high-sensitivity troponin, creatine kinase, high-sensitivity C-reactive protein, interleukin 6, D-dimer, ferritin, lactate dehydrogenase, and procalcitonin;and a high erythrocyte sedimentation rate were also associated with severe COVID-19. Conclusion: More than 30 risk factors are associated with a higher risk of severe COVID-19. These may serve as useful baseline parameters in the development of prediction tools for COVID-19 prognosis.