TIME MANAGEMENT AND RISK FACTORS IN LIFE-THREATENING ANCA-VASCULITIS

BackgroundAccuracy of diagnosis and prompt therapeutic intervention are the mainstay in patients with ANCA-associated vasculitis(AAV) suffering from life-threatening complications [1].However, there is no definition of therapeutic window in vital AAV, nor its impact on patient outcome regarding length of hospital stay, intensive care unit(ICU) admission or survival.ObjectivesThe aim of the study is to analyze the process of care from the perspective of time management in vital organ involvement AAV patients and to identify potential risk factors for ICU admission.MethodsA retrospective multicenter study identified AAV patients with life-threatening organ involvement, defined as alveolar hemorrhage, rapidly progressive renal failure, myocarditis and cerebral granuloma. Demographic data was collected. Key time frames were recorded, namely the interval from acute symptom onset to hospital presentation, days until imaging(plain X-ray, cardiac ultrasound, CT-scan), time to therapeutic intervention with corticosteroids or biologic/non-biologic immunosuppression(cyclophosphamide or rituximab) and to renal replacement therapy(RRT) or plasmapheresis. Time to ICU admission, hospital length-of-stay, Birmingham Vasculitis Activity Score(BVAS) were also noted. Statistical analysis was performed using SPSS and Chi-square and Pearson correlation tests were applied.Results66 patients with AAV were enrolled, out of which 17 fulfilled inclusion criteria. Mean age in the study group was 58.6±11.1 years old,10 patients(58.8%) were females and 7 (41.2%) males.11(64.7%) patients were c-ANCA positive, while 6 (35.3%) had p-ANCA and all were diagnosed with AAV prior to life-threatening event. Two patients had COVID-19 triggered AAV.In the study group, the most frequent critical organ suffering was rapidly progressive renal failure(12), followed by alveolar hemorrhages(10), 2 cerebral granulomas and one acute myocarditis. Three patients(17.6%) had more than one vital manifestation. Ten patients(58.8%) had more than three additional non-organ-threatening manifestations. Mean interval from AAV diagnosis to emergency admission was 30.1± 61.1 days, median 3 and from severe episode onset to hospitalization 1.65±0.18 days, median 1. There was only one death in the study group. Three patients were admitted in the ICU in 0.59±1.5 days following hospital presentation and required either RRT or plasma exchange within 2.66 days. Imaging examination was performed unanimously the day upon hospital admission. All patients received corticosteroids in the first 5.95±14.3 days, while immunosuppression was given to 13(76.5%) patients within 11.5±15.5 days from hospitalization.12 patients(70.5%) suffered from associated infections. Mean BVAS(13.6±6.76) correlated to ICU admission(p 0.013, r 0.58).Patients in ICU revealed higher BVAS(22±9.53) versus non-ICU(11.8±4.76).Hospital length of stay was 14.7±10.7 days(median 14) and showed no relationship to the type of severe organ involvement. The need for ICU caring was dominant in males(p 0.05) and confirmed in patients with proteinuria(p 0.012) and at least two major organ damage.ConclusionThis study shows that severity risk factors for potential ICU admission for life-threatening AAV appear to be male gender, proteinuria and the number of affected organs.Moreover, BVAS should be considered a useful tool to predict patients' risk for intensive care management since a higher score indicates a more aggressive disease.However, time to investigational or therapeutic intervention did not correlate to patient outcome in AAV.References[1]Geetha, D., Seo, P. (2011). Life-Threatening Presentations of ANCA-Associated Vasculitis. In: Khamashta, M., Ramos-Casals, M. (eds) Autoimmune Diseases. Springer, London. https://doi.org/10.1007/978-0-85729-358-9_8Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Microbiome in the Framework of Predictive, Preventive and Personalised Medicine

The human body is inhabited by trillions of diverse microorganisms collectively called "microbiome" or "microbiota". Microbiota consists of bacteria, viruses, fungi, protozoa, and archaea. Microbiome demonstrates multi-faceted effects on human physical and mental health. Per evidence there is a multi-functional interplay between the whole-body microbiome composition on the epithelial surfaces including skin, nasal and oral cavities, airway, gastro-intestinal and urogenital tracts on one hand and on the other hand, the individual health status. Microbiota composition as well as an option to modulate it - together create a highly attractive operation area for the translational bio/medical research with multi-professional expertise and healthcare-relevant output in the framework of predictive, preventive and personalised medicine (PPPM/3 PM). Advanced PPPM strategies implemented in the microbiome area are expected to significantly improve individual outcomes and overall cost-efficacy of healthcare. According to the accumulated research data, corresponding diagnostic and treatment approaches are applicable to primary care (health risk assessment in individuals with sub-optimal health conditions and prevention of a disease development), secondary care (personalised treatment of clinically manifested disorders preventing a disease progression) and tertiary care (making palliation to an optimal management of non-curable diseases). In the current book, we do highlight the implementation potential of the microbiome-relevant research in the framework of predictive diagnostics, targeted prevention and treatments tailored to the individualised patient profile.Copyright © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

The way forward: For patients, healthcare providers, and research

This chapter summarizes key information and formulate guiding principles to move forward and achieve a better understanding and management of long COVID. Long COVID has become a catch-all term for a huge variety of symptoms that are the result of an infection with SARS-CoV-2. Lingering symptoms in hospitalized patients are generally related to well-defined organ damage, what we have termed long-COVID disease;the subsequent medical course is similar to that of any severely ill patient. Although there are many symptoms associated with long COVID, fatigue is almost always a primary problem. There is no simple test to confirm the diagnosis of long COVID, and the diagnosis is made based on a patient's symptoms. Patients with severe symptoms will require multidisciplinary evaluation and care. Long-COVID care should be based on shared decision-making and includes patient self-monitoring and self-management. © 2023 John Wiley & Sons Ltd. All rights reserved.

The Latest Cellular and Molecular Mechanisms of COVID-19 on Non-Lung Organs.

Understanding the transmission pathways of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will aid in developing effective therapies directed at the virus's life cycle or its side effects. While severe respiratory distress is the most common symptom of a coronavirus 2019 (COVID-19) infection, the virus is also known to cause damage to almost every major organ and system in the body. However, it is not obvious whether pathological changes in extra-respiratory organs are caused by direct infection, indirect, or combination of these effects. In this narrative review, we first elaborate on the characteristics of SARS-CoV-2, followed by the mechanisms of this virus on various organs such as brain, eye, and olfactory nerve and different systems such as the endocrine and gastrointestinal systems.

Targeting neutrophils extracellular traps (NETs) reduces multiple organ injury in a COVID-19 mouse model.

BACKGROUND: COVID-19 is characterized by severe acute lung injury, which is associated with neutrophil infiltration and the release of neutrophil extracellular traps (NETs). COVID-19 treatment options are scarce. Previous work has shown an increase in NETs release in the lung and plasma of COVID-19 patients suggesting that drugs that prevent NETs formation or release could be potential therapeutic approaches for COVID-19 treatment. METHODS: Here, we report the efficacy of NET-degrading DNase I treatment in a murine model of COVID-19. SARS-CoV-2-infected K18-hACE2 mice were performed for clinical sickness scores and lung pathology. Moreover, the levels of NETs were assessed and lung injuries were by histopathology and TUNEL assay. Finally, the injury in the heart and kidney was assessed by histopathology and biochemical-specific markers. RESULTS: DNase I decreased detectable levels of NETs, improved clinical disease, and reduced lung, heart, and kidney injuries in SARS-CoV-2-infected K18-hACE2 mice. Furthermore, our findings indicate a potentially deleterious role for NETs lung tissue in vivo and lung epithelial (A549) cells in vitro, which might explain part of the pathophysiology of severe COVID-19. This deleterious effect was diminished by the treatment with DNase I. CONCLUSIONS: Together, our results support the role of NETs in COVID-19 immunopathology and highlight NETs disruption pharmacological approaches as a potential strategy to ameliorate COVID-19 clinical outcomes.

Case report: Area of focus in a case of malignant hypertension.

Malignant hypertension (MH) is characterized by severe hypertension (usually grade 3) associated with fundoscopic changes (flame hemorrhages and/or papilledema), microangiopathy and disseminated intravascular coagulation. In addition encephalopathy, acute heart failure and acute deterioration in renal function may be present. The term "malignant" reflects the very poor prognosis for this condition if untreated. When severe hypertension is associated with hypertension-mediated organ damage (HMOD) a life-threatening situation that requires immediate but careful intervention occurs (hypertensive emergency). In the last few years an increase in the number of patients with malignant hypertension has been observed, especially among those patients with black ethnicity. Limited access to treatment and the poor adherence to anti-hypertensive therapy may contribute to the development of hypertensive emergencies. It is considered appropriate to study patients in order to rule out thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. In fact, the microvascular damage caused by malignant hypertension can favor intravascular hemolysis like Thrombotic Microangiopathies (TMs). TMs may present in three different clinical conditions: typical hemolytic uremic syndrome (HUS), atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP). TMs can arise in the context of other pathological processes, including malignant hypertension.

Simulation of COVID-19 symptoms in a genetically engineered mouse model: implications for the long haulers.

The ongoing pandemic (also known as coronavirus disease-19; COVID-19) by a constantly emerging viral agent commonly referred as the severe acute respiratory syndrome corona virus 2 or SARS-CoV-2 has revealed unique pathological findings from infected human beings, and the postmortem observations. The list of disease symptoms, and postmortem observations is too long to mention; however, SARS-CoV-2 has brought with it a whole new clinical syndrome in "long haulers" including dyspnea, chest pain, tachycardia, brain fog, exercise intolerance, and extreme fatigue. We opine that further improvement in delivering effective treatment, and preventive strategies would be benefited from validated animal disease models. In this context, we designed a study, and show that a genetically engineered mouse expressing the human angiotensin converting enzyme 2; ACE-2 (the receptor used by SARS-CoV-2 agent to enter host cells) represents an excellent investigative resource in simulating important clinical features of the COVID-19. The ACE-2 mouse model (which is susceptible to SARS-CoV-2) when administered with a recombinant SARS-CoV-2 spike protein (SP) intranasally exhibited a profound cytokine storm capable of altering the physiological parameters including significant changes in cardiac function along with multi-organ damage that was further confirmed via histological findings. More importantly, visceral organs from SP treated mice revealed thrombotic blood clots as seen during postmortem examination. Thus, the ACE-2 engineered mouse appears to be a suitable model for studying intimate viral pathogenesis thus paving the way for identification, and characterization of appropriate prophylactics as well as therapeutics for COVID-19 management.

Clinical characteristics of 365 hospitalized COVID-19 patients with neurological symptoms: an observational study.

OBJECTIVE: Since the beginning of the COVID-19 pandemic, a number of COVID-related neurological manifestations have been reported. We aimed to categorize the features of hospitalized COVID-19 patients who experienced neurological symptoms. METHODS: In this descriptive, cross-sectional study, we enrolled all patients hospitalized with COVID-19 who experienced neurological symptoms in two hospitals in Tehran. Diagnosis of COVID-19 was established by PCR tests or computed tomography of the chest combined with COVID-19 clinical findings. The clinical characteristics, laboratory data, and imaging findings from 365 patients were analyzed. RESULTS: The average patient age was 59.2 ± 16.7 years and included 213 males and 152 females. The most prevalent neurological symptoms were headache (56.2%), impaired consciousness (55%), and dizziness (20.5%). During hospitalization, most of the patients did not require mechanical ventilation (81.9%). The percentage of patients with end-organ damage was 9% and mortality was 15%. Regression analysis on the neurological symptoms indicated that the mortality rate of patients with headaches was 84% lower than for the other neurological symptoms. Hyperglycemia was significantly related with end-organ damage and mortality (p = 0.029, p = 0.08, respectively). New vascular lesions were evident on brain MRIs of 9 patients and brain CTs of 16 patients. CONCLUSION: Among the neurological symptoms of patients with COVID-19, headache appeared to indicate a protective factor against development of end-organ damage as well as mortality.

Dysregulated Interferon Response and Immune Hyperactivation in Severe COVID-19: Targeting STATs as a Novel Therapeutic Strategy.

A disease outbreak in December 2019, caused by a novel coronavirus SARS-CoV-2, was named COVID-19. SARS-CoV-2 infects cells from the upper and lower respiratory tract system and is transmitted by inhalation or contact with infected droplets. Common clinical symptoms include fatigue, fever, and cough, but also shortness of breath and lung abnormalities. Still, some 5% of SARS-CoV-2 infections progress to severe pneumonia and acute respiratory distress syndrome (ARDS), with pulmonary edema, acute kidney injury, and/or multiple organ failure as important consequences, which can lead to death. The innate immune system recognizes viral RNAs and triggers the expression of interferons (IFN). IFNs activate anti-viral effectors and components of the adaptive immune system by activating members of the STAT and IRF families that induce the expression of IFN-stimulated genes (ISG)s. Among other coronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV, common strategies have been identified to antagonize IFN signaling. This typically coincides with hyperactive inflammatory host responses known as the "cytokine storm" that mediate severe lung damage. Likewise, SARS-CoV-2 infection combines a dysregulated IFN response with excessive production of inflammatory cytokines in the lungs. This excessive inflammatory response in the lungs is associated with the local recruitment of immune cells that create a pathogenic inflammatory loop. Together, it causes severe lung pathology, including ARDS, as well as damage to other vulnerable organs, like the heart, spleen, lymph nodes, and kidney, as well as the brain. This can rapidly progress to multiple organ exhaustion and correlates with a poor prognosis in COVID-19 patients. In this review, we focus on the crucial role of different types of IFN that underlies the progression of SARS-CoV-2 infection and leads to immune cell hyper-activation in the lungs, exuberant systemic inflammation, and multiple organ damage. Consequently, to protect from systemic inflammation, it will be critical to interfere with signaling cascades activated by IFNs and other inflammatory cytokines. Targeting members of the STAT family could therefore be proposed as a novel therapeutic strategy in patients with severe COVID-19.

Gasdermin-D activation by SARS-CoV-2 triggers NET and mediate COVID-19 immunopathology.

BACKGROUND: The release of neutrophil extracellular traps (NETs) is associated with inflammation, coagulopathy, and organ damage found in severe cases of COVID-19. However, the molecular mechanisms underlying the release of NETs in COVID-19 remain unclear. OBJECTIVES: We aim to investigate the role of the Gasdermin-D (GSDMD) pathway on NETs release and the development of organ damage during COVID-19. METHODS: We performed a single-cell transcriptome analysis in public data of bronchoalveolar lavage. Then, we enrolled 63 hospitalized patients with moderate and severe COVID-19. We analyze in blood and lung tissue samples the expression of GSDMD, presence of NETs, and signaling pathways upstreaming. Furthermore, we analyzed the treatment with disulfiram in a mouse model of SARS-CoV-2 infection. RESULTS: We found that the SARS-CoV-2 virus directly activates the pore-forming protein GSDMD that triggers NET production and organ damage in COVID-19. Single-cell transcriptome analysis revealed that the expression of GSDMD and inflammasome-related genes were increased in COVID-19 patients. High expression of active GSDMD associated with NETs structures was found in the lung tissue of COVID-19 patients. Furthermore, we showed that activation of GSDMD in neutrophils requires active caspase1/4 and live SARS-CoV-2, which infects neutrophils. In a mouse model of SARS-CoV-2 infection, the treatment with disulfiram inhibited NETs release and reduced organ damage. CONCLUSION: These results demonstrated that GSDMD-dependent NETosis plays a critical role in COVID-19 immunopathology and suggests GSDMD as a novel potential target for improving the COVID-19 therapeutic strategy.

Tissue repair strategies: What we have learned from COVID-19 in the application of MSCs therapy.

Coronavirus disease 2019 (COVID-19) infection evokes severe proinflammatory storm and pulmonary infection with the number of confirmed cases (more than 200 million) and mortality (5 million) continue to surge globally. A number of vaccines (e.g., Moderna, Pfizer, Johnson/Janssen and AstraZeneca vaccines) have been developed over the past two years to restrain the rapid spread of COVID-19. However, without much of effective drug therapies, COVID-19 continues to cause multiple irreversible organ injuries and is drawing intensive attention for cell therapy in the management of organ damage in this devastating COVID-19 pandemic. For example, mesenchymal stem cells (MSCs) have exhibited promising results in COVID-19 patients. Preclinical and clinical findings have favored the utility of stem cells in the management of COVID-19-induced adverse outcomes via inhibition of cytokine storm and hyperinflammatory syndrome with coinstantaneous tissue regeneration capacity. In this review, we will discuss the existing data with regards to application of stem cells for COVID-19.

The Additive Value of Cardiovascular Magnetic Resonance in Convalescent COVID-19 Patients.

In COVID-19 the development of severe viral pneumonia that is coupled with systemic inflammatory response triggers multi-organ failure and is of major concern. Cardiac involvement occurs in nearly 60% of patients with pre-existing cardiovascular conditions and heralds worse clinical outcome. Diagnoses carried out in the acute phase of COVID-19 rely upon increased levels of circulating cardiac injury biomarkers and transthoracic echocardiography. These diagnostics, however, were unable to pinpoint the mechanisms of cardiac injury in COVID-19 patients. Identifying the main features of cardiac injury remains an urgent yet unmet need in cardiology, given the potential clinical consequences. Cardiovascular magnetic resonance (CMR) provides an unparalleled opportunity to gain a deeper insight into myocardial injury given its unique ability to interrogate the properties of myocardial tissue. This endeavor is particularly important in convalescent COVID-19 patients as many continue to experience chest pain, palpitations, dyspnea and exertional fatigue, six or more months after the acute illness. This review will provide a critical appraisal of research on cardiovascular damage in convalescent adult COVID-19 patients with an emphasis on the use of CMR and its value to our understanding of organ damage.

Effects of SARS-CoV-2 Inflammation on Selected Organ Systems of the Human Body.

INTRODUCTION AND PURPOSE OF THE STUDY: SARS-CoV-2 virus does not only affect the respiratory system. It may cause damage to many organ systems with long-term effects. The latest scientific reports inform that this virus leaves a long-term trace in the nervous, circulatory, respiratory, urinary and reproductive systems. It manifests itself in disturbances in the functioning of the organs of these systems, causing serious health problems. The aim of the study was to review the latest research into the long-term effects of COVID-19 and determine how common these symptoms are and who is most at risk. Based on a literature review using the electronic scientific databases of PubMed and Web of Science on the long-term effects of SARS-CoV-2 infection, 88 studies were included in the analysis. The information contained in the analyzed literature shows that the SARS-CoV-2 virus can cause multi-organ damage, causing a number of long-term negative health complications. CONCLUSIONS: There is evidence that the virus can cause long-term complications lasting more than six months. They mainly concern disturbances in the functioning of the nervous, circulatory and respiratory systems. However, these studies are small or short-lasting, and many are speculative.

Defense of COVID-19 by Human Organoids.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has created an immense menace to public health worldwide, exerting huge effects on global economic and political conditions. Understanding the biology and pathogenesis mechanisms of this novel virus, in large parts, relies on optimal physiological models that allow replication and propagation of SARS-CoV-2. Human organoids, derived from stem cells, are three-dimensional cell cultures that recapitulate the cellular organization, transcriptional and epigenetic signatures of their counterpart organs. Recent studies have indicated their great values as experimental virology platforms, making human organoid an ideal tool for investigating host-pathogen interactions. Here, we summarize research developments for SARS-CoV-2 infection of various human organoids involved in multiple systems, including lung, liver, brain, intestine, kidney and blood vessel organoids. These studies help us reveal the pathogenesis mechanism of COVID-19, and facilitate the development of effective vaccines and drugs as well as other therapeutic regimes.

Single-Cell and Bulk RNASeq Profiling of COVID-19 Patients Reveal Immune and Inflammatory Mechanisms of Infection-Induced Organ Damage.

The SARS-CoV-2 virus's ability to induce hypercytokinemia and cause multiple organ failure makes it imperative to find effective treatments. To understand the mechanism of viral infection and its effects on organ tissues, we analyzed multiple single-cell and bulk RNAseq data from COVID-19 patients' organ samples. Various levels of severity of infection were accounted for, with comparative analyses between mild, moderate, and severely infected patients. Our analysis uncovered an upregulation of the innate immune response via several inflammatory genes, IL-2, IL-6, IL-8, IL-17A, and NF-κB. Consequently, we found that the upregulation of these downstream effects can lead to organ injury. The downregulated pathways such as eukaryotic initiation factor 2 (eIF2) and eIF4-mediated host translation, were found to lead to an increased viral translation. We also found that the loss of inhibitory peptides can suppress an overactive innate immune response via NF-κB and interleukin-mediated pathways. Investigation of viral-host protein mapping showed that the interaction of viral proteins with host proteins correlated with the down- and upregulation of host pathways such as decreased eIF2-mediated host translation and increased hypertrophy and fibrosis. Inflammation was increased via the stimulation of pro-inflammatory cytokines and suppression of host translation pathways that led to reduced inflammatory inhibitors. Cardiac hypertrophy and organ fibrosis were the results of increased inflammation in organs of severe and critical patients. Finally, we identified potential therapeutic targets for the treatment of COVID-19 and its deleterious effects on organs. Further experimental investigation would conclusively determine the effects of COVID-19 infection on organs other than the lungs and the effectiveness of the proposed therapeutic targets.

An Insight to ncovid-19 associated coagulopathy.

Several current studies have highlighted the high occurrence of coagulopathy in nCOVID-19 infection. The corona virus often prompts hypercoagulability along with both microangiopathy and local thrombus development, and systemic coagulation limitation which causes large vessel thrombosis and key thromboembolic issues such as pulmonary embolism in seriously ill hospitalized patients. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of nCOVID-19. The clinical presentation of nCOVID-19-associated coagulopathy is organ dysfunction primarily, while hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D-dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. Overall, the patients have an increase in venous and arterial thrombotic events especially in ICU patients. Routine thromboprophylaxis with low molecular weight heparin is recommended in all hospitalized patients to reduce the incidence of thrombosis. Though, the importance of thromboembolic impediments has not been extensively spotlighted, thus the rationale of this article is to provide recent information about this severe difficulty. In this article the mechanism of coagulopathy, associated problems and possible therapeutics has been reviewed.

Correlation Between Relative Nasopharyngeal Virus RNA Load and Lymphocyte Count Disease Severity in Patients with COVID-19.

The aim of this study was to analyze the correlation between dynamic changes in the nasopharyngeal viral load of patients infected with the new coronavirus causing pneumonia and lymphocyte count disease severity. Cases newly diagnosed with COVID-19 at the First Affiliated Hospital of Nanchang University from January 2020 to February 2020 were analyzed retrospectively. Quantitative real-time polymerase chain reaction was used to determine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from throat swab sample ΔCT values; lymphocyte and lymphocyte subset counts, coagulation system factor levels, myocardial injury indexes, and laboratory biochemical indicators were compared between the mild group and the severe group. The correlation between the relative load of nasopharyngeal SARS-CoV-2 RNA and severe disease symptoms was analyzed. Of the 76 patients, 49 were male and 27 were female. The lymphocyte, CD4+ T lymphocyte, and CD8+ T lymphocyte counts all differed significantly between the two groups (p < 0.001), as did differences in interleukin (IL)-2R, IL-6, and IL-8 levels (p = 0.022, 0.026, and 0.012, respectively). Moreover, there were significant differences in prothrombin time, D-dimer, and fibrinogen levels between the mild group and the severe group (p = 0.029, 0.006, and <0.001, respectively), and in lactate dehydrogenase and troponin (p < 0.001 and p = 0.007, respectively). SARS-CoV-2 RNA load and lymphocyte count, CD4+ T lymphocyte count, and CD8+ T lymphocyte count were linearly negatively correlated (p < 0.001). SARS-CoV-2 RNA load was positively correlated with IL-2R, prothrombin time, lactate dehydrogenase, and hypersensitive troponin T (p = 0.002, p = 0.009, and p < 0.001, respectively). In addition, the time that it took for the nucleic acid test to turn negative was significantly shorter for patients in the mild group than for those in the severe group (Z = -6.713, p < 0.001). In conclusion, relative SARS-CoV-2 RNA load in the nasopharynx is closely related to COVID-19 severity. If the relative RNA load was higher, the lymphocyte count was lower, organ damage was greater, and the time it took for the nucleic acid test to turn negative was longer.

Mucormycosis: An opportunistic pathogen during COVID-19.

The pandemic of coronavirus disease 2019 (COVID-19) still remains on an upsurge trend. The second wave of this disease has led to panic in many countries, including India and some parts of the world suffering from the third wave. As there are no proper treatment options or remedies available for this deadly infection, supportive care equipment's such as oxygen cylinders, ventilators and heavy use of steroids play a vital role in the management of COVID-19. In the midst of this pandemic, the COVID-19 patients are acquiring secondary infections such as mucormycosis also known as black fungus disease. Mucormycosis is a serious, but rare opportunistic fungal infection that spreads rapidly, and hence prompt diagnosis and treatment are necessary to avoid high rate of mortality and morbidity rates. Mucormycosis is caused by the inhalation of its filamentous (hyphal form) fungi especially in the patients who are immunosuppressed. Recent studies have documented alarming number of COVID-19 patients with mucormycosis infection. Most of these patients had diabetes and were administered steroids for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and were consequently more prone to mucormycosis. Hence, the present review emphasizes mucormycosis and its related conditions, its mechanism in normal and COVID-19 affected individuals, influencing factors and challenges to overcome this black mold infection. Early identification and further investigation of this fungus will significantly reduce the severity of the disease and mortality rate in COVID-19 affected patients.

Untangling COVID-19 and autoimmunity: Identification of plausible targets suggests multi organ involvement.

Underlying mechanisms of multi-organ manifestations and exacerbated inflammation in COVID-19 are yet to be delineated. The hypothesis of SARS-CoV-2 triggering autoimmunity is gaining attention and, in the present study, we have identified 28 human proteins harbouring regions homologous to SARS-CoV-2 peptides that could possibly be acting as autoantigens in COVID-19 patients displaying autoimmune conditions. Interestingly, these conserved regions are amongst the experimentally validated B cell epitopes of SARS-CoV-2 proteins. The reported human proteins have demonstrated presence of autoantibodies against them in typical autoimmune conditions which may explain the frequent occurrence of autoimmune conditions following SARS-CoV-2 infection. Moreover, the proposed autoantigens' widespread tissue distribution is suggestive of their involvement in multi-organ manifestations via molecular mimicry. We opine that our report may aid in directing subsequent necessary antigen-specific studies, results of which would be of long-term relevance in management of extrapulmonary symptoms of COVID-19.