Autophagy and SARS-CoV-2-Old Players in New Games.

At present it is well-defined that autophagy is a fundamental process essential for cell life but its pro-viral and anti-viral role has been stated out with the COVID pandemic. However, viruses in turn have evolved diverse adaptive strategies to cope with autophagy driven host defense, either by blocking or hijacking the autophagy machinery for their own benefit. The mechanisms underlying autophagy modulation are presented in the current review which summarizes the accumulated knowledge on the crosstalk between autophagy and viral infections, with a particular emphasizes on SARS-CoV-2. The different types of autophagy related to infections and their molecular mechanisms are focused in the context of inflammation. In particular, SARS-CoV-2 entry, replication and disease pathogenesis are discussed. Models to study autophagy and to formulate novel treatment approaches and pharmacological modulation to fight COVID-19 are debated. The SARS-CoV-2-autophagy interplay is presented, revealing the complex dynamics and the molecular machinery of autophagy. The new molecular targets and strategies to treat COVID-19 effectively are envisaged. In conclusion, our finding underline the importance of development new treatment strategies and pharmacological modulation of autophagy to fight COVID-19.

Japan MG registry: Chronological surveys over 10years

The primary purpose of the Japanese myasthenia gravis registry (JAMG‐R) has been to research and promote high‐quality medical care for MG patients in Japan. We reviewed the findings of surveys performed by JAMG‐R over an ~10‐y period. The first goal for favorable quality of life (QOL) is a status of minimal manifestations (MM) or better with an oral prednisolone (PSL) dose of 5 mg/d or less (MM‐5 mg). Early and aggressive use of nonoral fast‐acting treatment together with low‐dose oral PSL (the "EFT strategy”) is recommended to reduce disease severity with minimal oral steroid use so that the MM‐5 mg target can be met as soon as possible. We conducted the fourth largest multicenter survey ever in 2021, obtaining detailed clinical information from 1710 consecutive MG patients all over Japan, and compared the 2021 surveys with those from 2012 and 2015. The frequency of patients treated with EFT strategies showed a gradual increase, reaching 39% of the total MG patients in the 2021 survey. The current and maximum dose of PSL and the number of days at high‐dose (>20 mg/d) PSL showed decreases. Survey results indicate that as EFT strategies have spread, the percentage of patients on MM‐5 mg has increased. We again confirmed that MM‐5 mg was associated with favorable QOL in the 2021 survey. Recent data regarding COVID‐19 suggests that it did not seriously impact the MG population in Japan;unfortunately, refractory MG, observed in 21% of patients, is still an unresolved problem.

Clinical and pathogenic features of COVID-19-associated diarrhea syndrome

The article systematizes the results of research in key areas of the problem of diarrhea, associated with COVID-19, analyzes the current ideas about the clinical characteristics, pathogenic mechanisms and relationships with the development of dysbiotic changes and inflammatory bowel diseases, accepted in practice and promising treatment strategies. © 2022 Organizational Psychology. All rights reserved.

Japan MG registry: Chronological surveys over 10 years

The primary purpose of the Japanese myasthenia gravis registry (JAMG‐R) has been to research and promote high‐quality medical care for MG patients in Japan. We reviewed the findings of surveys performed by JAMG‐R over an ~10‐y period. The first goal for favorable quality of life (QOL) is a status of minimal manifestations (MM) or better with an oral prednisolone (PSL) dose of 5 mg/d or less (MM‐5 mg). Early and aggressive use of nonoral fast‐acting treatment together with low‐dose oral PSL (the “EFT strategy”) is recommended to reduce disease severity with minimal oral steroid use so that the MM‐5 mg target can be met as soon as possible. We conducted the fourth largest multicenter survey ever in 2021, obtaining detailed clinical information from 1710 consecutive MG patients all over Japan, and compared the 2021 surveys with those from 2012 and 2015. The frequency of patients treated with EFT strategies showed a gradual increase, reaching 39% of the total MG patients in the 2021 survey. The current and maximum dose of PSL and the number of days at high‐dose (>20 mg/d) PSL showed decreases. Survey results indicate that as EFT strategies have spread, the percentage of patients on MM‐5 mg has increased. We again confirmed that MM‐5 mg was associated with favorable QOL in the 2021 survey. Recent data regarding COVID‐19 suggests that it did not seriously impact the MG population in Japan;unfortunately, refractory MG, observed in 21% of patients, is still an unresolved problem. [ FROM AUTHOR] Copyright of Clinical & Experimental Neuroimmunology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

COVID-19 Pandemic: Assessment of Current Strategies and Socio-economic Impact

The coronavirus disease is a respiratory tract disorder which causes pneumonia-like symptoms in severe patients and mild flu-like symptoms in mild symptomatic cases first noticed in Wuhan, China. DNA sequencing and further analysis shows it to be 79% like the 2002 SARS-CoV and 50% like the 2012 MERS-CoV. It was also observed that the novel coronavirus’s spike protein was larger and very different from its previously known strains. For diagnosis, multiple strategies were developed and real time reverse-transcriptase-polymerase chain reaction (RT-PCR) technique was determined to be the best technique. The CT scan was also found effective majorly for the continuous assessment of the disease. Treatment strategies used in previous outbreaks were looked into and put to trial like convalescent plasma therapy. Vaccine development using various genetic engineering strategies are going on across the world. To contain the spread of the disease, countries with positive cases were put under lockdown to break the chain of spread. These lockdowns forced industries, offices, schools, religious places, stadiums, travel, and many more to close which impacted the economies of all the major countries. Lesser human interaction and more use of social media has impacted the social aspects of human life. Cases of domestic violence and mental stress increased among households. Economic stimulus package was announced by various countries to curb the socio-economic impact of the COVID-19 pandemic. © 2022 SAGE Publications.

Treatment Strategies and Perforation Rate of Acute Appendicitis During the Early Phase of the COVID-19 Pandemic: A Swedish Cohort Study.

INTRODUCTION: It is unknown whether the COVID-19 pandemic has had an impact on emergency surgical care in Sweden. This study aimed to compare frequency, treatment strategies, severity, and complication rate of appendicitis during the initial phase of the COVID-19 pandemic with those of previous years. METHODS: In this single-center study, we identified all patients admitted with appendicitis between March 16 and June 16, 2020, at the Stockholm South General Hospital, and compared these with patients hospitalized with appendicitis during the same calendar period the three previous years. We used multivariate logistic regression to calculate Odds Ratios (OR) with 95% confidence intervals as measurement of the association between appendicitis treatment and perforation rate during the COVID-19 period compared to the nonCOVID-19 periods. RESULTS: In all, 892 patients hospitalized with appendicitis were identified, 241 (27%) in 2020 (Covid period group) and the remaining 651 (73%) during the same calendar periods 2017-2019 (nonCovid period group). Appendicitis during the COVID-19 period was associated with double the risk for undergoing conservative treatment (OR 2.15 [95% CI 1.44-3.21]), and a decreased risk for being diagnosed with perforated appendicitis (OR 0.68 [95% CI 0.48-0.98]). CONCLUSIONS: Patients admitted with appendicitis during the early phase of the COVID-19 pandemic in Stockholm, Sweden, were more likely to receive conservative treatment and less likely to suffer from perforated appendicitis compared to patients hospitalized before the pandemic. Hypothetically, this difference could have been due to pandemic-associated resource reallocation, or it may simply reflect an increasing trend towards conservative management of appendicitis.

Pathogenesis and Treatment of Cytokine Storm Induced by Infectious Diseases.

Cytokine storm is a phenomenon characterized by strong elevated circulating cytokines that most often occur after an overreactive immune system is activated by an acute systemic infection. A variety of cells participate in cytokine storm induction and progression, with profiles of cytokines released during cytokine storm varying from disease to disease. This review focuses on pathophysiological mechanisms underlying cytokine storm induction and progression induced by pathogenic invasive infectious diseases. Strategies for targeted treatment of various types of infection-induced cytokine storms are described from both host and pathogen perspectives. In summary, current studies indicate that cytokine storm-targeted therapies can effectively alleviate tissue damage while promoting the clearance of invading pathogens. Based on this premise, "multi-omics" immune system profiling should facilitate the development of more effective therapeutic strategies to alleviate cytokine storms caused by various diseases.

Using in silico viral kinetic models to guide therapeutic strategies during a pandemic: An example in SARS-CoV-2.

AIMS: We propose the use of in silico mathematical models to provide insights that optimize therapeutic interventions designed to effectively treat respiratory infection during a pandemic. A modelling and simulation framework is provided using SARS-CoV-2 as an example, considering applications for both treatment and prophylaxis. METHODS: A target cell-limited model was used to quantify the viral infection dynamics of SARS-CoV-2 in a pooled population of 105 infected patients. Parameter estimates from the resulting model were used to simulate and compare the impact of various interventions against meaningful viral load endpoints. RESULTS: Robust parameter estimates were obtained for the basic reproduction number, viral release rate and infected-cell mortality from the infection model. These estimates were informed by the largest dataset currently available for SARS-CoV-2 viral time course. The utility of this model was demonstrated using simulations, which hypothetically introduced inhibitory or stimulatory drug mechanisms at various target sites within the viral life-cycle. We show that early intervention is crucial to achieving therapeutic benefit when monotherapy is administered. In contrast, combination regimens of two or three drugs may provide improved outcomes if treatment is initiated late. The latter is relevant to SARS-CoV-2, where the period between infection and symptom onset is relatively long. CONCLUSIONS: The use of in silico models can provide viral load predictions that can rationalize therapeutic strategies against an emerging viral pathogen.

Evaluation of the Pharmacologic Treatment of COVID-19 Pandemic in Iraq.

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, or COVID-19) has been detrimental to human health, economy, and wellbeing. Little information is known on the epidemiology and outcome of the disease in a localized community within Iraq. We carried out an audit of confirmed cases of COVID-19 in the Kirkuk General Hospital. Data from the 20th of June to the 31st of July, 2020, were collected and analyzed. Suspected COVID-19 cases were confirmed by real-time polymerase chain reaction (RT-PCR). Data on clinical symptoms, age, and treatment protocols were analyzed concerning the outcome. Our study included a total of 200 individual confirmed COVID-19 patients. The majority of cases 55% (n = 110) displayed severe symptoms, while 32.5% (65 cases) and 12.5% (25 cases) of patients displayed moderate to mild symptoms, respectively. The rate of death in the referred patients was 5%. Most patients admitted to the hospital for treatment recovered and were discharged from the hospital within 5 to 30 days post-diagnosis. Statistical analysis revealed that patients treated with oseltamivir, hydroxychloroquine, and azithromycin in combination with vitamins C and D have shorter hospital stay compared to patients receiving the same therapeutic protocol in combination with steroids. Moreover, a higher mortality rate (4.5%) was observed in patients treated with oseltamivir, hydroxychloroquine, ceftriaxone, and steroids. This study highlights a significant relationship between age, secondary ailments, and the choice of medications as simple predictors of the outcome of COVID-19.

A review of COVID-19: Treatment strategies and CRISPR/Cas9 gene editing technology approaches to the coronavirus disease.

The new coronavirus SARS-CoV-2 pandemic has put the world on lockdown for the first time in decades. This has wreaked havoc on the global economy, put additional burden on local and global public health resources, and, most importantly, jeopardised human health. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and the CRISPR associated (Cas) protein (CRISPR/Cas) was identified to have structures in E. coli. The most modern of these systems is CRISPR/Cas. Editing the genomes of plants and animals took several years and cost hundreds of thousands of dollars until the CRISPR approach was discovered in 2012. As a result, CRISPR/Cas has piqued the scientific community's attention, particularly for disease diagnosis and treatment, because it is faster, less expensive, and more precise than previous genome editing technologies. Data from gene mutations in specific patients gathered using CRISPR/Cas can aid in the identification of the best treatment strategy for each patient, as well as other research domains such as coronavirus replication in cell culture, such as SARS-CoV2. The implications of the most prevalent driver mutations, on the other hand, are often unknown, making treatment interpretation difficult. For detecting a wide range of target genes, the CRISPR/Cas categories provide highly sensitive and selective tools. Genome-wide association studies are a relatively new strategy to discovering genes involved in human disease when it comes to the next steps in genomic research. Furthermore, CRISPR/Cas provides a method for modifying non-coding portions of the genome, which will help advance whole genome libraries by speeding up the analysis of these poorly defined parts of the genome.

Cardiovascular consequences of viral infections: from COVID to other viral diseases.

Infection of the heart muscle with cardiotropic viruses is one of the major aetiologies of myocarditis and acute and chronic inflammatory cardiomyopathy (DCMi). However, viral myocarditis and subsequent dilated cardiomyopathy is still a challenging disease to diagnose and to treat and is therefore a significant public health issue globally. Advances in clinical examination and thorough molecular genetic analysis of intramyocardial viruses and their activation status have incrementally improved our understanding of molecular pathogenesis and pathophysiology of viral infections of the heart muscle. To date, several cardiotropic viruses have been implicated as causes of myocarditis and DCMi. These include, among others, classical cardiotropic enteroviruses (Coxsackieviruses B), the most commonly detected parvovirus B19, and human herpes virus 6. A newcomer is the respiratory virus that has triggered the worst pandemic in a century, SARS-CoV-2, whose involvement and impact in viral cardiovascular disease is under scrutiny. Despite extensive research into the pathomechanisms of viral infections of the cardiovascular system, our knowledge regarding their treatment and management is still incomplete. Accordingly, in this review, we aim to explore and summarize the current knowledge and available evidence on viral infections of the heart. We focus on diagnostics, clinical relevance and cardiovascular consequences, pathophysiology, and current and novel treatment strategies.

Analysis of Traditional Chinese Medicine Diagnosis and Treatment Strategies for COVID-19 Based on "The Diagnosis and Treatment Program for Coronavirus Disease-2019" from Chinese Authority.

In December 2019, coronavirus disease-2019 (COVID-19) broke out in Wuhan and other places. Seven versions of the Diagnosis and Treatment Program for Coronavirus Disease-2019 successively issued by the Chinese government have designated traditional Chinese medicine (TCM) as a necessary medical strategy. Based on the changes in TCM diagnosis and treatment strategies in these seven versions of Diagnosis and Treatment Program for Coronavirus Disease-2019, this paper collected data reported by the Chinese government media; analyzed the understanding of the etiology, pathogenesis, syndrome differentiation, treatment methods, and prescriptions of COVID-19 by TCM and evaluated the clinical efficacy of TCM strategies. COVID-19 is associated with TCM disease of pestilence, and its pathogenesis can be summarized as an "epidemic pathogen invading the body, followed by entering the internal organs and transforming into heat, resulting in pathogen trapping in the interior and healthy qi collapsing, and deficiency of qi and yin". Pathological processes should be emphasized in syndrome differentiation. The manifestations of qi deficiency and yin deficiency are exhibited during the recovery period. TCM strategies represented by Qing Fei Pai Du Tang have shown apparent advantages in improving symptoms, promoting virus clearance, and shortening hospitalization, as well as surprising efficacy of zero patient progressing from mild to severe cases in a TCM cabin hospital. Clinical data illustrate the effectiveness of TCM strategies proposed by the Chinese government. This major epidemic may bring new opportunities for TCM development.

Treatment strategies of hospitalized patients with coronavirus disease-19.

With the outbreak of coronavirus disease-19 (COVID-19), Changsha faced an increasing burden of treating the Wuhan migrants and their infected patients. This study is a retrospective, single-center case series of the 238 consecutive hospitalized patients with confirmed COVID-19 at the First Hospital of Changsha city, China, from 01/21 to 02/14, 2020; the final date of follow-up was 02/27, 2020. Of 238 patients 43.7% visited Wuhan, 58.4% got in touch with Wuhan people, and 47.5% had contacted with diagnosed patients. 37.8% patients had family members infected. 190 cases had mild / general disease, and 48 cases had severe / critical disease. Compared to mild or general patients, more severe or critical patients visited Wuhan (59.6% vs 40.2%; P=0.02) and contacted with Wuhan people (74.5% vs 55.0%; P=0.02). All patients received antiviral treatment, including Lopinavir / Ritonavir (29.3%), Interferon (14.6%) and their combination (40.6%), Arbidol (6.7%), Xuebijing (7.1%) and Chloroquine phosphate (1.3%). Severe and critical patients received glucocorticoid, Gamma-globulin and oxygen inhalation. Some received mechanic ventilation support. As of 02/27, 161 patients discharged. The median length of hospital stay was 13 days. The 10-, 14-, 20- and 28-day discharge rate was 19.1%, 42.8%, 65.0% and 76.4%, respectively. No hospital-related transmission was observed.

Similarities and Dissimilarities of COVID-19 and Other Coronavirus Diseases.

In less than two decades, three deadly zoonotic coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2, have emerged in humans, causing SARS, MERS, and coronavirus disease 2019 (COVID-19), respectively. The current COVID-19 pandemic poses an unprecedented crisis in health care and social and economic development. It reinforces the cruel fact that CoVs are constantly evolving, possessing the genetic malleability to become highly pathogenic in humans. In this review, we start with an overview of CoV diseases and the molecular virology of CoVs, focusing on similarities and differences between SARS-CoV-2 and its highly pathogenic as well as low-pathogenic counterparts. We then discuss mechanisms underlying pathogenesis and virus-host interactions of SARS-CoV-2 and other CoVs, emphasizing the host immune response. Finally, we summarize strategies adopted for the prevention and treatment of CoV diseases and discuss approaches to develop effective antivirals and vaccines.

Management of Coronavirus Disease 2019 (COVID-19) Pandemic: From Diagnosis to Treatment Strategies.

Following the emergence of severe acute respiratory syndrome (SARS) in 2002 and the Middle East respiratory syndrome (MERS) in 2012, the world is now combating a third large-scale outbreak caused by a coronavirus, the coronavirus disease 2019 (COVID-19). After the rapid spread of SARS-coronavirus (CoV)-2 (the virus causing COVID-19) from its origin in China, the World Health Organization (WHO) declared a Public Health Emergency of International Concern (PHEIC) on January 30, 2020. From the beginning of the COVID-19 pandemic, a significant number of studies have been conducted to better understand the biology and pathogenesis of the novel coronavirus, and to aid in developing effective treatment regimens, therapeutics, and vaccines. This review focuses on the recent advancements in the rapidly evolving areas of clinical care and management of COVID-19. The emerging strategies for the diagnosis and treatment of this disease are explored, and the development of effective vaccines is reviewed.

Real Clinical Practice and Therapeutic Management Following COVID-19 Crisis in two Hospitals in Iran: A Statistical and Conceptual View.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) outbreak quickly has spread and became a pandemic. However, no approved therapeutics or effective treatment is available for the treatment of these patients. The present study was done to retrospectively assess the treatment strategies (e.g., pharmaceutical care services) for COVID-19 patients in selected hospitals and highlight the importance of such services in the management of a pandemic. MATERIALS AND METHODS: Data from a series of COVID-19 patients (978 patients; 658 males [66.9%] and 324 females [33.1%]) admitted to the selected hospitals in Tehran from 20 February to 19 March 2020 were retrieved retrospectively from the Health Information System (HIS) of the hospitals. The statistical tests were used for analyzing the effect and correlation of the variables (drugs) with the average length of stay (ALOS) in the hospital. RESULTS: Diverse medication classes and old drugs with or without strong evidence of therapeutic effects against the novel coronavirus, some previously tried as a treatment for SARS-CoV and MERS-CoV, were mostly used for the treatment of patients in the hospitals. Many medications (broad-spectrum antibiotics and antivirals) or combination therapies are used without evidence of their therapeutic effects during pandemics. CONCLUSION: Therefore, guidelines should be provided for the off-label use of these drugs by policymakers and stakeholders during a pandemic emergency due to high demands. Also, monitoring of the HIS data can play an important role in improving public health response to emerging diseases.

Virology, pathogenesis, diagnosis and in-line treatment of COVID-19.

SARS-CoV-2, a newly emerged pathogen in December 2019, marked as one of the highly pathogenic Coronavirus, and altogether this is the third coronavirus attack that crossed the species barrier. As of 1st July 2020, it is spreading around 216 countries, areas or territories, and a total of 10,185,374 and 503,862 confirmed cases and death reports, respectively. The SARS-CoV-2 virus entered into the target cells by binding with the hACE2 receptors. Spike glycoprotein promotes the entry of the virus into host target cells. Literature reported a significant mutation in receptor binding sites and membrane proteins of the previous SARS-CoV to turned as SARS-CoV-2 virus, responsible for most dreadful pandemic COVID-19. These modifications may be the probable reason for the extreme transmission and pathogenicity of the virus. A hasty spread of COVID-19 throughout the world is highly threatening, but still, scientists do not have a proper therapeutic measure to fight with it. Scientists are endeavoring across the world to find effective therapy to combat COVID 19. Several drugs such as Remdesivir, Hydroxychloroquine, Chloroquine, Ribavirin, Ritonavir, Lopinavir, Favipiravir, Interferons, Bevacizumab, Azithromycin, etc. are currently under clinical trials. Vaccine development from various pharmaceutical companies and research institutes is under progress, and more than ten vaccine candidates are in the various phases of clinical trials. This review work highlighted the origin, emergence, structural features, pathogenesis, and clinical features of COVID-19. We have also discussed the in-line treatment strategies, preventive measures, and vaccines to combat the emergence of COVID-19.

Coronavirus disease 2019 in the elderly: Clinical characteristics, diagnosis and treatment strategies. / 老年2019å† çŠ¶ç— æ¯’ç— çš„ä¸´åºŠç‰¹ç‚¹ä¸Žè¯Šç–—ç­–ç•¥.

Many countries in the world have faced with coronavirus disease 2019 (COVID-19) epidemic since December 2019, while the proportion of elderly patients with COVID-19 in severe and death cases is relatively high. At present, China is in the rapid development stage of population aging, and the demand of the elderly for medical care, health care, nursing and life services far exceeds that of other people. Especially in the period of COVID-19, it is particularly urgent to summarize more experience and methods in time to reduce the infection rate, the incidence of critical illness, and the mortality rate. Therefore, this review combines the existing research results with clinic experience of diagnosis and treatment for senile infectious diseases, summarizes the clinical characteristics and puts forward the prevention strategies of elderly COVID-19 patients, which provide evidence for effective prevention and treatment of COVID-19 in elderly patients, improvement of cure rate, and reduction of severe incidence rate and mortality.