Coronavirus disease 2019 (COVID-19), an acute onset pneumonia caused by a novel Betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly evolved into a pandemic. Though its origin has been linked to the Wuhan City of China's Hubei Province in December 2019, recent reports claim that the original animalto-human transmission of the virus probably happened sometime between September and October 2019 in Guangdong Province, rather than Hubei. As of July 3, 2020, India has reported a case positivity rate of 6.5% and a fatality rate of 2.8%, which are among the lowest in the world. Also, the severity of the disease is much less among Indians as evidenced by the low rate of ICU admission (15.3%) and the need for mechanical ventilation (4.16%). As per the World Health Organization (WHO) situation report 165 on July 3, 2020, India has one of the lowest deaths per 100,000 population (1.32 deaths against a global average of 6.04). Several factors related to the pathogen, host and environment might have some role in reducing the susceptibility of Indians to COVID-19. These include some ongoing mutations that can alter the virulence of the circulating SARS-CoV-2 strains, host factors like innate immunity, genetic diversity in immune responses, epigenetic factors, genetic polymorphisms of ACE2 receptors, micro RNAs and universal BCG vaccination, and environmental factors like high temperature and humidity which may alter the viability and transmissibility of the strain. This perspective-highlights the potential factors that might be responsible for the observed low COVID-19 fatality rate in Indian population. It puts forward several hypotheses which can be a ground for future studies determining individual and population susceptibility to COVID-19 and thus, may offer a new dimension to our current understanding of the disease.
Coronavirus disease 2019 (COVID-19) is a major public health problem worldwide. These patients are at increased risk of developing secondary infections due to a combination of virus- and drug-induced immunosuppression. Recently, several countries have reported an emergence of COVID-19 associated mucormycosis (CAM), particularly among patients with uncontrolled diabetes, with India reporting an alarming increase in rhino-orbito-cerebral mucormycosis (ROCM) in post-COVID cases. Hyperglycemia and diabetic ketoacidosis (DKA) are the major underlying risk factors. So far, case reports and review articles have reported CAM only in adult patients. Here, we describe the first cases of COVID-19-associated ROCM in two pediatric patients with Type 1 diabetes mellitus (DM). Both the cases had asymptomatic infection with SARS-CoV-2 and developed ROCM during the course of treatment of DKA. None of them had exposure to systemic steroids. Imaging findings in both cases revealed involvement of orbit, paranasal sinuses, and brain with cavernous sinus thrombosis. The patients underwent craniotomy with evacuation of abscess. Microbiological and histopathological findings were consistent with the diagnosis of mycormycosis, with fungal culture growing Rhizopus arrhizus . Post-operatively, the patients received liposomal amphotericin B (LAMB) and systemic antibiotics. Retrobulbar injection of LAMB was given in an attempt to halt orbital disease progression. However, it wasn't successful and both of them had to undergo orbital exenteration eventually. ROCM is a rapidly progressive disease and prompt diagnosis with aggressive surgery and timely initiation of antifungal therapy can be life-saving. Physicians should have a high index of suspicion, so as to avoid a delayed diagnosis, particularly in post-COVID patients with uncontrolled diabetes.
Coronavirus disease 2019 (COVID-19), an acute onset pneumonia caused by a novel Betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in the Wuhan City of China in December 2019 and evolved into a global pandemic. To date, there are no proven drugs or vaccines against this virus. Hence, the situation demands an urgent need to explore all potential therapeutic strategies that can be made available to prevent the disease progression and improve patient outcomes. In absence of clinically proven treatment guidelines, several repurposed drugs and investigational agents are currently being evaluated in clinical trials for their probable benefits in the treatment of COVID-19. These include antivirals (remdesivir, lopinavir/ ritonavir, umifenovir, and favipiravir), interferon, antimalarials (chloroquine/ hydroxychloroquine), antiparasitic drugs (ivermectin and nitazoxanide), biologics (monoclonal antibodies and interleukin receptor antagonist), cellular therapies (mesenchymal stem cells and natural killer cells), convalescent plasma, and cytokine adsorber. Though several observational studies have claimed many of these agents to be effective based on their in vitro activities and extrapolated evidence from SARS and Middle East respiratory syndrome (MERS) epidemics, the currently available data remains inconclusive because of ill-defined patient selection criteria, small sample size, lack of concurrent controls, and use of intermediary outcomes instead of patient-relevant outcomes. Moreover, there is a need to clearly define the patient populations who warrant therapy and also the timing of initiation of treatment. Understanding the disease pathology responsible for the clinical manifestations of COVID-19 is imperative to identify the potential targets for drug development. This review explains the pathophysiology of COVID-19 and summarizes the potential treatment candidates, which can provide guidance in developing effective therapeutic strategies.
With the emergence of second wave of COVID-19 infection globally, particularly in India in March–April 2021, protection by massive vaccination drive has become the need of the hour. Vaccines have been proved to reduce the risk of developing severe illness and are emerging as vital tools in the battle against COVID-19. As per the GLOBOCAN database, nearly 19.3 million new cancer cases have been reported in 2020 globally, which posed a significant challenge to health care providers to protect such large number of ‘vulnerable’ patients from COVID-19. Nevertheless, a considerable degree of doubt, hesitancy and misconceptions are noted regarding the administration of vaccines particularly during active immuno-suppressant treatment. This review article highlights the added vulnerability of cancer patients to the COVID-19 infection and has explored the immunological challenges associated with malignancy, anticancer treatment and COVID-19 vaccination. Supplementary Information The online version contains supplementary material available at 10.1007/s12032-021-01540-8.
The genus Apophysomyces belonging to the order Mucorales is increasingly being reported as a cause of mucormycosis in immunocompetent patients. We report a case of necrotizing fasciitis caused by Apophysomyces variabilis in a 52-year-old immunocompetent male who sustained thermal burn in his right leg following a road-traffic accident. There was rapidly progressive necrosis of skin, soft tissues and underlying muscles which required extensive surgical debridement. Microscopic examination of excised tissues revealed broad aseptate fungal hyphae. Fungal culture on Sabouraud dextrose agar (SDA) showed growth of a mucoraceous mould which was identified as A. variabilis based on characteristic microscopic morphology and internal transcribed spacer sequencing of the ribosomal DNA. The isolate was found to sporulate on SDA, a finding that was unique as Apophysomyces spp. does not usually sporulate on primary isolation medium used in mycology laboratories. The disease progressed as there was an initial assumption of bacterial infection and the fungus was isolated late in the course of the disease because of which no antifungal drug was added to the regime. The patient left against medical advice and eventually underwent below-knee amputation at another city hospital a week later. Infection due to A. variabilis should be considered as a differential diagnosis of rapidly progressive necrosis of skin and soft tissues in immunocompetent individuals as early diagnosis and management will prevent the disease progression and a possible amputation.
Recently, the global emergence of emergomycosis, a systemic fungal infection caused by a novel dimorphic fungus Emergomyces species has been observed among immunocompromised individuals. Though initially classified under the genus Emmonsia, a taxonomic revision in 2017 based on DNA sequence analyses placed five Emmonsia-like fungi under a separate genus Emergomyces. These include Emergomyces pasteurianus, Emergomyces africanus, Emergomyces canadensis, Emergomyces orientalis, and Emergomyces europaeus. Emmonsia parva was renamed as Blastomyces parvus, while Emmonsia crescens and Emmonsia sola remained within the genus Emmonsia until a taxonomic revision in 2020 placed both the species under the genus Emergomyces. However, unlike other members of the genus, Emergomyces crescens and Emergomyces sola do not cause disseminated disease. The former causes adiaspiromycosis, a granulomatous pulmonary disease, while the latter has not been associated with human disease. So far, emergomycosis has been mapped across four continents: Asia, Europe, Africa and North America. However, considering the increasing prevalence of HIV/AIDS, it is presumed that the disease must have a worldwide distribution with many cases going undetected. Diagnosis of emergomycosis remains challenging. It should be considered in the differential diagnosis of histoplasmosis as there is considerable clinical and histopathological overlap between the two entities. Sequencing the internal transcribed spacer region of ribosomal DNA is considered as the gold standard for identification, but its application is compromised in resource limited settings. Serological tests are non-specific and demonstrate cross-reactivity with Histoplasma galactomannan antigen. Therefore, an affordable, accessible, and reliable diagnostic test is the need of the hour to enable its diagnosis in endemic regions and also for epidemiological surveillance. Currently, there are no consensus guidelines for the treatment of emergomycosis. The recommended regimen consists of amphotericin B (deoxycholate or liposomal formulation) for 1–2 weeks, followed by oral itraconazole for at least 12 months. This review elaborates the taxonomic, clinical, diagnostic, and therapeutic aspects of emergomycosis. It also enumerates several novel antifungal drugs which might hold promise in the treatment of this condition and therefore, can be potential areas of future studies.
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