Betacoronavirus Severe Acute Respiratory Syndrome Research Articles

MicroRNA-185 Inhibits SARS-CoV-2 Infection through the Modulation of the Host's Lipid Microenvironment.

With the emergence of the novel betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there has been an urgent need for the development of fast-acting antivirals, particularly in dealing with different variants of concern (VOC). SARS-CoV-2, like other RNA viruses, depends on host cell machinery to propagate and misregulate metabolic pathways to its advantage. Herein, we discovered that the immunometabolic microRNA-185 (miR-185) restricts SARS-CoV-2 propagation by affecting its entry and infectivity. The antiviral effects of miR-185 were studied in SARS-CoV-2 Spike protein pseudotyped virus, surrogate virus (HCoV-229E), as well as live SARS-CoV-2 virus in Huh7, A549, and Calu-3 cells. In each model, we consistently observed microRNA-induced reduction in lipid metabolism pathways-associated genes including SREBP2, SQLE, PPARG, AGPAT3, and SCARB1. Interestingly, we also observed changes in angiotensin-converting enzyme 2 (ACE2) levels, the entry receptor for SARS-CoV-2. Taken together, these data show that miR-185 significantly restricts host metabolic and other pathways that appear to be essential to SAR-CoV-2 replication and propagation. Overall, this study highlights an important link between non-coding RNAs, immunometabolic pathways, and viral infection. miR-185 mimics alone or in combination with other antiviral therapeutics represent possible future fast-acting antiviral strategies that are likely to be broadly antiviral against multiple variants as well as different virus types of potential pandemics.

The Effect of Glycosylation Modulators on the Trafficking and Interaction of Spike Protein S1 Subunit and Angiotensin‐Converting Enzyme 2

The betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the cause of the ongoing worldwide pandemic. The spike (S) glycoprotein of SARS‐CoV‐2 is a heavily glycosylated trimer that binds to host cell receptor angiotensin‐converting enzyme 2 (ACE2), initiating viral entry. Evidence also shows that the S glycoprotein interacts with other receptors including dipeptidyl peptidase IV (DPPIV). Glycosylation is a post‐translational modification important for proper folding and trafficking of membrane and secretory proteins. It plays a critical role not only for host cell proteins, but also in viral virulence, immunity evasion and receptor binding capabilities. This study focused on the modulation of glycosylation and its effects on the trafficking of the S1 subunit, ACE2 and DPPIV, in addition to its effect on their interactions. For this purpose, the S1 subunit was expressed in COS‐1 cells in the presence or absence of N‐butyldeoxynojirimycin (NB‐DNJ), an inhibitor of the ER‐located a‐glucosidases I and II, 1‐deoxymannojirimycin (dMM), an inhibitor of Golgi‐mannosidase I, or benzyl‐N‐acetyl‐α‐galactosaminide (benzyl‐GalNac), an inhibitor of O‐glycosylation. The data demonstrate that NB‐DNJ affects substantially the trafficking and secretion of S1 protein, while its overall synthetic levels remained unchanged. A similar effect was observed upon treatment of the cells with the benzyl‐GalNac. On the contrary, the presence of dMM in the culture medium did not affect the secretion of S1. Together, the data suggest that folding events implicating calnexin in the ER, the site of action of NB‐DNJ, as well as O‐glycans that are modulated by benzyl‐GalNac are crucial for the secretion of the S1 protein. We further investigated the trafficking of ACE2 and DPPIV in lung Calu‐3 and intestinal Caco‐2 cells in the presence or absence of the glycosylation modulators and their interaction with S1. The data demonstrate a reduced binding capacity of S1 to ACE2 in the presence of NB‐DNJ and dMM, while this interaction was enhanced in Calu‐3 cells upon inhibition of O‐glycosylation by benzyl‐GalNac. We conclude that glycosylation modulators differentially act on the secretory pathway of S1 and the receptors. By virtue of its negative impact on both the secretion of S1 as well as interaction with its receptor ACE2, NB‐DNJ may be considered as a potential therapeutic drug that may act at the level of viral entry and exit.

Exosomes Recovered From the Plasma of COVID-19 Patients Expose SARS-CoV-2 Spike-Derived Fragments and Contribute to the Adaptive Immune Response.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by beta-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has rapidly spread across the globe starting from February 2020. It is well established that during viral infection, extracellular vesicles become delivery/presenting vectors of viral material. However, studies regarding extracellular vesicle function in COVID-19 pathology are still scanty. Here, we performed a comparative study on exosomes recovered from the plasma of either MILD or SEVERE COVID-19 patients. We show that although both types of vesicles efficiently display SARS-CoV-2 spike-derived peptides and carry immunomodulatory molecules, only those of MILD patients are capable of efficiently regulating antigen-specific CD4+ T-cell responses. Accordingly, by mass spectrometry, we show that the proteome of exosomes of MILD patients correlates with a proper functioning of the immune system, while that of SEVERE patients is associated with increased and chronic inflammation. Overall, we show that exosomes recovered from the plasma of COVID-19 patients possess SARS-CoV-2-derived protein material, have an active role in enhancing the immune response, and possess a cargo that reflects the pathological state of patients in the acute phase of the disease.

Molecular Modeling and Preliminary Clinical Data Suggesting Antiviral Activity for Chlorpheniramine (Chlorphenamine) Against COVID-19.

Chlorpheniramine maleate, a widely used over-the-counter antihistamine, has been identified as a structural analog of aminoquinolines known to possess antiviral activity against the Betacoronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). Structural similarities include the chlorophenyl group, pyridine ring, alkyl sidechain, and terminal tertiary amine; the comparison of aqueous energy-minimized structures indicates significant three-dimensional similarity as well. Preliminary clinical evidence supports these conclusions. The present study suggests that chlorpheniramine possesses antiviral activity against COVID-19.

Evaluation of neutralizing antibodies after vaccine BNT162b2: Preliminary data.

It is well-known that the Coronavirus Disease 2019, which is caused by the beta-coronavirus severe acute respiratory syndrome (SARS-CoV-2), emerged in December 2019 followed by an outbreak first reported in Wuhan, China. Thus far, vaccination appears to be the only way to bring the pandemic to an end. In the present study, immunogenicity data was evaluated using LIAISON® SARS-CoV-2 TrimericS IgG assay (DiaSorin S.p.A) among a sample of 52 vaccinated healthcare workers, five of whom were previously infected with SARS-CoV-2 and 47 who were seronegative, over a time span of ≤90 days following the second dose of the BNT162b2 mRNA vaccine. The test detects antibodies against the Trimeric complex (S1, S2 and receptor binding domain). The overall mean value of the serum levels of IgG antibodies to SARS-CoV-2 30 days following the second dose of the vaccine was 1,901.8 binding arbitrary unit (BAU)/ml, after 60 days the mean value declined to 1,244.9 BAU/ml. The antibody levels then reached a plateau, as confirmed by the antibody test carried out 90 days following the second dose, which revealed a mean value of 1,032.4 BAU/ml (P<0.0001). A higher level was observed at all three times in male subjects compared with female subjects, and in younger male participants compared with female participants, although these differences did not reach a statistically significant level. Similarly, no significant difference was found in antibody values at different times according to age. After the second dose of the vaccine, two subjects were infected with SARS-CoV-2, and an increase in antibody values in the third assay was observed in both individuals.

Measuring the Effects of COVID-19 on Women’s Daily Lives and Well-Being: A National Survey’s Preliminary Results

The emergence of COVID-19, the disease caused by severe acute respiratory syndrome betacoronavirus (SARS-CoV-2), in the United States since March 2020 has had a profound effect on daily life . Schools and colleges were forced to pivot in-person instruction to "online only" teaching, learning, and advising , with little advance notice. Businesses and corporations moved swiftly to accommodate remote working, telecommuting, and other flexible scheduling offers. Yet, many were forced to downsize, furlough, or terminate workers due to loss revenue, resulting in record-breaking rates of unemployment, forced displacement, homelessness, and food insecurities .

COVID-19 : VACCINES AND ITS DETRIMENTAL EFFECTS

COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus strain. The most common symptoms of COVID-19 are fever, dry cough, and tiredness. Other symptoms that are less common and may affect some patients include loss of taste or smell, aches and pains, headache, sore throat, nasal congestion, red eyes, diarrhoea, or a skin rash. The Novel Beta-Coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is responsible for causing a worldwide pandemic (COVID-19) after emerging in Wuhan, China. The World Health Organization declared SARS-2 COVID-19 as a global pandemic on the 11th of March 2020. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until September 2nd 2021, has caused more than 45,44,546 deaths. Hence, laboratories worldwide have developed and are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality.

Neutrophils and lymphopenia, an unknown axis in severe COVID-19 disease.

The Coronavirus Disease 2019 (COVID-19) is caused by the betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus that can mediate asymptomatic or fatal infections characterized by pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. Several studies have highlighted the importance of B and T lymphocytes, given that neutralizing antibodies and T cell responses are required for an effective immunity. In addition, other reports have described myeloid cells such as macrophages and monocytes play a major role in the immunity against SARS-CoV-2 as well as dysregulated pro-inflammatory signature that characterizes severe COVID-19. During COVID-19, neutrophils have been defined as a heterogeneous group of cells, functionally linked to severe inflammation and thrombosis triggered by degranulation and NETosis, but also to suppressive phenotypes. The physiological role of suppressive neutrophils during COVID-19 and their implications in severe disease have been poorly studied and is not well understood. Here, we discuss the current evidence regarding the role of neutrophils with suppressive properties such as granulocytic myeloid-derived suppressor cells (G-MDSCs) and their possible role in suppressing CD4+ and CD8+ T lymphocytes expansion and giving rise to lymphopenia in severe COVID-19 infection.

Structural Dissection of Viral Spike-Protein Binding of SARS-CoV-2 and SARS-CoV-1 to the Human Angiotensin-Converting Enzyme 2 (ACE2) as Cellular Receptor.

An outbreak by a new severe acute respiratory syndrome betacoronavirus (SARS-CoV-2) has spread CoronaVirus Disease 2019 (COVID-19) all over the world. Immediately, following studies have confirmed the human Angiotensin-Converting Enzyme 2 (ACE2) as a cellular receptor of viral Spike-Protein (Sp) that mediates the CoV-2 invasion into the pulmonary host cells. Here, we compared the molecular interactions of the viral Sp from previous SARS-CoV-1 of 2002 and SARS-CoV-2 with the host ACE2 protein by in silico analysis of the available experimental structures of Sp-ACE2 complexes. The K417 amino acid residue, located in the region of Sp Receptor-Binding Domain (RBD) of the new coronavirus SARS-CoV-2, showed to have a key role for the binding to the ACE2 N-terminal region. The R426 residue of SARS-CoV-1 Sp-RBD also plays a key role, although by interacting with the central region of the ACE2 sequence. Therefore, our study evidenced peculiarities in the interactions of the two Sp-ACE2 complexes. Our outcomes were consistent with previously reported mutagenesis studies on SARS-CoV-1 and support the idea that a new and different RBD was acquired by SARS-CoV-2. These results have interesting implications and suggest further investigations.

Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after emerging in Wuhan, China. Here we analyzed public host and viral RNA sequencing data to better understand how SARS-CoV-2 interacts with human respiratory cells. We identified genes, isoforms and transposable element families that are specifically altered in SARS-CoV-2-infected respiratory cells. Well-known immunoregulatory genes including CSF2, IL32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were upregulated. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and eukaryotic initiation factor 4 (eIF4b). We also identified a viral sequence variant with a statistically significant skew associated with age of infection, that may contribute to intracellular host–pathogen interactions. These findings can help identify host mechanisms that can be targeted by prophylactics and/or therapeutics to reduce the severity of COVID-19.

Influenza virus and SARS-CoV-2: pathogenesis and host responses in the respiratory tract.

Influenza viruses cause annual epidemics and occasional pandemics of respiratory tract infections that produce a wide spectrum of clinical disease severity in humans. The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and has since caused a pandemic. Both viral and host factors determine the extent and severity of virus-induced lung damage. The host’s response to viral infection is necessary for viral clearance but may be deleterious and contribute to severe disease phenotypes. Similarly, tissue repair mechanisms are required for recovery from infection across the spectrum of disease severity; however, dysregulated repair responses may lead to chronic lung dysfunction. Understanding of the mechanisms of immunopathology and tissue repair following viral lower respiratory tract infection may broaden treatment options. In this Review, we discuss the pathogenesis, the contribution of the host response to severe clinical phenotypes and highlight early and late epithelial repair mechanisms following influenza virus infection, each of which has been well characterized. Although we are still learning about SARS-CoV-2 and its disease manifestations in humans, throughout the Review we discuss what is known about SARS-CoV-2 in the context of this broad knowledge of influenza virus, highlighting the similarities and differences between the respiratory viruses.

A narrative review of coronavirus disease 2019 (COVID-19): clinical, epidemiological characteristics, and systemic manifestations.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease which has had a rapid surge in cases and deaths since it is first documented in Wuhan, China, in December 2019. COVID-19 is caused by the Betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 uses angiotensin-converting enzyme 2, which is highly expressed in the human lower respiratory tract but also in other tissues, as the cellular entry receptor. Thus, COVID-19 mainly affects the respiratory system but can cause damage to other body systems, including the cardiovascular, gastrointestinal, hepatobiliary, renal, and central nervous systems. We review the pathogenesis and clinical manifestations of the infection, focusing on our current understanding of the disease mechanisms and their translation to clinical outcomes, as well as adverse effects on different body systems. We also discuss the epidemiology pathogenesis, clinical, and multi-organ consequences, and highlight some of the research gaps regarding COVID-19.

COVID-19, leprosy, and neutrophils.

Coronavirus Disease 2019 (COVID-19), a disease caused by the betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has only recently emerged, while Mycobacterium leprae, the etiological agent of leprosy, has endured for more than 2,000 years. As soon as the initial reports of COVID-19 became public, several entities, including the Brazilian Leprosy Society, warned about the possible impact of COVID-19 on leprosy patients. It has been verified that COVID-19 carriers can be either asymptomatic or present varying degrees of severe respiratory failure in association with cytokine storm and death, among other diseases. Severe COVID-19 patients show increased numbers of neutrophils and serum neutrophil extracellular trap (NET) markers, in addition to alterations in the neutrophil-to-lymphocyte ratio (NLR). The absence of antiviral drugs and the speed of COVID-19 transmission have had a major impact on public health systems worldwide, leading to the almost total collapse of many national and local healthcare services. Leprosy, an infectious neurological and dermatological illness, is widely considered to be the most frequent cause of physical disabilities globally. The chronic clinical course of the disease may be interrupted by acute inflammatory episodes, named leprosy reactions. These serious immunological complications, characterized by cytokine storms, are responsible for amplifying peripheral nerve damage. From 30% to 40% of all multibacillary leprosy (MB) patients experience erythema nodosum leprosum (ENL), a neutrophilic immune-mediated condition. ENL patients often present these same COVID-19-like symptoms, including high levels of serum NET markers, altered NLR, and neutrophilia. Moreover, the consequences of a M. leprae–SARS-CoV-2 coinfection have yet to be fully investigated. The goal of the present viewpoint is to describe some of the similarities that may be found between COVID-19 and leprosy disease in the context of neutrophilic biology.

Functionalized terahertz plasmonic metasensors: Femtomolar-level detection of SARS-CoV-2 spike proteins

Effective and efficient management of human betacoronavirus severe acute respiratory syndrome (SARS)-CoV-2 virus infection i.e., COVID-19 pandemic, required sensitive and selective sensors with short sample-to-result durations for performing desired diagnostics. In this direction, one appropriate alternative approach to detect SARS-CoV-2 virus protein at low level i.e., femtomolar (fM) is exploring plasmonic metasensor technology for COVID-19 diagnostics, which offers exquisite opportunities in advanced healthcare programs, and modern clinical diagnostics. The intrinsic merits of plasmonic metasensors stem from their capability to squeeze electromagnetic fields, simultaneously in frequency, time, and space. However, the detection of low-molecular weight biomolecules at low densities is a typical drawback of conventional metasensors that has recently been addressed using toroidal metasurface technology. This research is focused on the fabrication of a miniaturized plasmonic immunosensor based on toroidal electrodynamics concept that can sustain robustly confined plasmonic modes with ultranarrow lineshapes in the terahertz (THz) frequencies. By exciting toroidal dipole mode using our quasi-infinite metasurface and a judiciously optimized protocol based on functionalized gold nanoparticles (AuNPs) conjugated with the specific monoclonal antibody specific to spike protein (S1) of SARS-CoV-2 virus onto the metasurface, the resonance shifts for diverse concentrations of the spike protein are monitored. Possessing molecular weight around ~76 kDa allowed to detect the presence of SARS-CoV-2 virus protein with significantly low as limit of detection (LoD) was achieved as ~4.2 fM. We envisage that outcomes of this research will pave the way toward the use of toroidal metasensors as practical technologies for rapid and precise screening of SARS‐CoV‐2 virus carriers, symptomatic or asymptomatic, and spike proteins in hospitals, clinics, laboratories, and site of infection.

Rapid detection of SARS-CoV-2 with CRISPR-Cas12a.

The recent outbreak of betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is responsible for the Coronavirus Disease 2019 (COVID-19) global pandemic, has created great challenges in viral diagnosis. The existing methods for nucleic acid detection are of high sensitivity and specificity, but the need for complex sample manipulation and expensive machinery slow down the disease detection. Thus, there is an urgent demand to develop a rapid, inexpensive, and sensitive diagnostic test to aid point-of-care viral detection for disease monitoring. In this study, we developed a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated proteins (Cas) 12a-based diagnostic method that allows the results to be visualized by the naked eye. We also introduced a rapid sample processing method, and when combined with recombinase polymerase amplification (RPA), the sample to result can be achieved in 50 minutes with high sensitivity (1–10 copies per reaction). This accurate and portable detection method holds a great potential for COVID-19 control, especially in areas where specialized equipment is not available.

Suppression of SARS-CoV-2 infection in ex-vivo human lung tissues by targeting class III phosphoinositide 3-kinase.

The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged at the end of 2019 and caused the coronavirus disease 19 (COVID‐19) pandemic due to its high transmissibility and early immunosuppression. Previous studies on other betacoronaviruses suggested that betacoronavirus infection is associated with the host autophagy pathway. However, it is unclear whether any components of autophagy or virophagy can be therapeutic targets for COVID‐19 treatment. In this report, we examined the antiviral effect of four well‐characterized small molecule inhibitors that target the key cellular factors involved in key steps of the autophagy pathway. They include small molecules targeting the ULK1/Atg1 complex involved in the induction stage of autophagy (ULK1 inhibitor SBI0206965), the ATG14/Beclin1/VPS34 complex involved in the nucleation step of autophagy (class III PI3‐kinase inhibitor VPS34‐IN1), and a widely‐used autophagy inhibitor that persistently inhibits class I and temporary inhibits class III PI3‐kinase (3‐MA) and a clinically approved autophagy inhibitor that suppresses autophagy by inhibiting lysosomal acidification and prevents the formation of autophagolysosome (HCQ). Surprisingly, not all the tested autophagy inhibitors suppressed SARS‐CoV‐2 infection. We showed that inhibition of class III PI3‐kinase involved in the initiation step of both canonical and noncanonical autophagy potently suppressed SARS‐CoV‐2 at a nano‐molar level. In addition, this specific kinase inhibitor VPS34‐IN1, and its bioavailable analogue VVPS34‐IN1, potently inhibited SARS‐CoV‐2 infection in ex vivo human lung tissues. Taken together, class III PI3‐kinase may be a possible target for COVID‐19 therapeutic development.

Yeast-expressed SARS-CoV recombinant receptor-binding domain (RBD219-N1) formulated with aluminum hydroxide induces protective immunity and reduces immune enhancement

We developed a severe acute respiratory syndrome (SARS) subunit recombinant protein vaccine candidate based on a high-yielding, yeast-engineered, receptor-binding domain (RBD219-N1) of the SARS beta-coronavirus (SARS-CoV) spike (S) protein. When formulated with Alhydrogel®, RBD219-N1 induced high levels of neutralizing antibodies against both pseudotyped virus and a clinical (mouse-adapted) isolate of SARS-CoV. Here, we report that mice immunized with RBD219-N1/Alhydrogel® were fully protected from lethal SARS-CoV challenge (0% mortality), compared to ~30% mortality in mice immunized with the SARS S protein formulated with Alhydrogel®, and 100% mortality in negative controls. An RBD219-N1 formulation with Alhydrogel® was also superior to the S protein, unadjuvanted RBD, and AddaVax (MF59-like adjuvant)-formulated RBD in inducing specific antibodies and preventing cellular infiltrates in the lungs upon SARS-CoV challenge. Specifically, a formulation with a 1:25 ratio of RBD219-N1 to Alhydrogel® provided high neutralizing antibody titers, 100% protection with non-detectable viral loads with minimal or no eosinophilic pulmonary infiltrates. As a result, this vaccine formulation is under consideration for further development against SARS-CoV and potentially other emerging and re-emerging beta-CoVs such as SARS-CoV-2.

Modified rehabilitation exercises for mild cases of COVID-19.

Coronavirus disease 2019 (COVID-19) caused by a new Betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a global pandemic. Gathered clinicopathological evidence in COVID-19 patients shows that alveoli injuries and interstitial changes are the major mechanisms of impaired O2/CO2 exchange. Few rehabilitation exercises concerning COVID-19 patients were reported. Here, we present a modified version of rehabilitation exercises based on the underlying mechanism of the disease to mild cases of COVID-19. These exercises aimed to improve the pulmonary function of patients and ease the expectoration process. Additionally, an essential branch of Traditional Chinese Medicine (TCM) named acupressure was integrated into the exercises to facilitate the recovery and maintenance of pulmonary function. From March 4, 2020 to May 5, 2020, a total of 60 COVID-19 patients who completed the full course of MRE were enrolled in this observational study. The diagnostic and classification criteria were based on the 7th edition of Diagnosis and Treatment Guideline of COVID-19 published by the National Health Commission of the People's Republic of China. We prospectively gathered patients' reported outcomes concerning respiration-related symptoms at four different time points, including: (I) at admission; (II) at the time of hospital discharge; (III) two weeks after discharge; (IV) four weeks after discharge. The reported respiratory symptoms included dry cough, productive cough, difficulty in expectoration, and dyspnea. In total, 60 confirmed mild COVID-19 cases were enrolled with a median age of 54 years old. The baseline prevalence for dry cough, productive cough, difficulty in expectoration, and dyspnea were 41.7%, 43.3%, 35.0%, and 50.0%, respectively. The pronounced decline in symptom prevalence was recorded over time. Interestingly, four weeks after discharge, we noticed a lower remission rate in productive cough and difficulty in expectoration. The modified rehabilitation exercises were retrieved from the Eight-Section Brocade, and are specifically designed for rehabilitation of COVID-19 patients at home or health facilities. Based on current findings on pronouncedly improved remission rate in respiratory symptoms, we recommend the MRE as suitable rehabilitation exercise to smooth respiration and ease the expectoration process in mild COVID-19 cases.

Case Report: Use of hydroxychloroquine and N-acetylcysteine for treatment of a COVID-19 patient

There is worldwide concern for lack of specific therapy against the novel Betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This case report presents the results of a pharmacological intervention aimed at modulating the inflammatory effects of coronavirus disease 2019 (COVID-19), in an effort to avoid the use of mechanical ventilation. A COVID-19 positive patient was admitted with multisystem organ dysfunction, including acute respiratory insufficiency, and was treated with a combination of low oral doses of hydroxychloroquine and intravenous N-acetylcysteine (NAC). The combination therapy resulted in noticeable clinical improvement and a quantifiable decrease of several of the inflammatory markers measured, in particular ferritin levels, C-reactive protein (CRP) and lactic acid. He also developed pulmonary embolism (PE) and deep vein thrombosis (DVT), both known side effects of COVID-19 infection. Following thrombolysis and heparinization his clinical evolution continued a positive trend until discharge. The therapeutic approach utilized in this case suggests that early intervention not only decrease acute organ dysfunction but also may decrease the need for mechanical ventilation in COVID-19 positive patients.

The Enigma of Low COVID-19 Fatality Rate in India.

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 animal-to-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.