Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities.

Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.

Superrepellent Doubly Reentrant Geometry Promotes Antibiofouling and Prevention of Coronavirus Contamination.

The fomite transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has drawn attention because of its highly contagious nature. Therefore, surfaces that can prevent coronavirus contamination are an urgent and unmet need during the coronavirus disease 2019 (COVID-19) pandemic. Conventional surfaces are usually based on superhydrophobic or antiviral coatings. However, these coatings may be dysfunctional because of biofouling, which is the undesired adhesion of biomolecules. A superhydrophobic surface independent of the material content and coating agents may serve the purpose of antibiofouling and preventing viral transmission. Doubly reentrant topology (DRT) is a unique structure that can meet the need. This study demonstrates that the DRT surfaces possess a striking antibiofouling effect that can prevent viral contamination. This effect still exists even if the DRT surface is made of a hydrophilic material such as silicon oxide and copper. To the best of our knowledge, this work first demonstrates that fomite transmission of viruses may be prevented by minimizing the contact area between pathogens and surfaces even made of hydrophilic materials. Furthermore, the DRT geometry per se features excellent antibiofouling ability, which may shed light on the applications of pathogen elimination in alleviating the COVID-19 pandemic.

The Omicron variant wave: Where are we now and what are the prospects?

The Omicron variant BA.2 is the dominant form of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in many countries, including those that have already implemented the strictest quarantine mandates that effectively contained the spread of the previous variants. Although many individuals were partially or fully vaccinated, confirmed Omicron infections have far surpassed all other variants combined in just a couple of months since the Omicron variant emerged. The ChAdOx1-S (AstraZeneca), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) vaccines offer protection against the severe illness of SARS-CoV-2 infection; however, these currently available vaccines are less effective in terms of preventing Omicron infections. As a result, a booster dose of BNT162b2 or mRNA-1273 is recommended for individuals >12 years old who had received their second dose of the approved vaccines for >5 months. Herein, we review the studies that assessed the clinical benefits of the booster dose of vaccines against Omicron infections. We also analyzed public data to address whether early booster vaccination effectively prevented the surge of the Omicron infections. Finally, we discuss the consideration of a fourth dose of vaccine as a way to prevent possible upcoming infections.

Nature-Inspired Surface Structures Design for Antimicrobial Applications.

Surface contamination by microorganisms such as viruses and bacteria may simultaneously aggravate the biofouling of surfaces and infection of wounds and promote cross-species transmission and the rapid evolution of microbes in emerging diseases. In addition, natural surface structures with unique anti-biofouling properties may be used as guide templates for the development of functional antimicrobial surfaces. Further, these structure-related antimicrobial surfaces can be categorized into microbicidal and anti-biofouling surfaces. This review introduces the recent advances in the development of microbicidal and anti-biofouling surfaces inspired by natural structures and discusses the related antimicrobial mechanisms, surface topography design, material application, manufacturing techniques, and antimicrobial efficiencies.

Superrepellent Doubly Reentrant Geometry Promotes Antibiofouling and Prevention of Coronavirus Contamination

The fomite transmission of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has drawn attention because of its highly contagious nature. Therefore, surfaces that can prevent coronavirus contamination are an urgent and unmet need during the coronavirus disease 2019 (COVID‐19) pandemic. Conventional surfaces are usually based on superhydrophobic or antiviral coatings. However, these coatings may be dysfunctional because of biofouling, which is the undesired adhesion of biomolecules. A superhydrophobic surface independent of the material content and coating agents may serve the purpose of antibiofouling and preventing viral transmission. Doubly reentrant topology (DRT) is a unique structure that can meet the need. This study demonstrates that the DRT surfaces possess a striking antibiofouling effect that can prevent viral contamination. This effect still exists even if the DRT surface is made of a hydrophilic material such as silicon oxide and copper. To the best of our knowledge, this work first demonstrates that fomite transmission of viruses may be prevented by minimizing the contact area between pathogens and surfaces even made of hydrophilic materials. Furthermore, the DRT geometry per se features excellent antibiofouling ability, which may shed light on the applications of pathogen elimination in alleviating the COVID‐19 pandemic. The findings demonstrate that a unique fabricated doubly reentrant topology (DRT) structure carries remarkable superrepellent properties against biofouling of protein, blood, bacteria, and viruses. Moreover, this characteristic results from a highly minimized contact area and still exists even if the DRT surface is made of a hydrophilic material, such as silicon oxide.

Evaluation of the diagnostic accuracy of COVID-19 antigen tests: A systematic review and meta-analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to affect countries worldwide. To inhibit the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), testing of patients, contact tracing, and quarantine of their close contacts have been used as major nonpharmaceutical interventions. The advantages of antigen tests, such as low cost and rapid turnaround, may allow for the rapid identification of larger numbers of infectious persons. This meta-analysis aimed to evaluate the diagnostic accuracy of antigen tests for SARS-CoV-2. METHODS: We searched PubMed, Embase, Cochrane Library, and Biomed Central databases from inception to January 2, 2021. Studies evaluating the diagnostic accuracy of antigen testing for SARS-CoV-2 with reference standards were included. We included studies that provided sufficient data to construct a 2 × 2 table on a per-patient basis. Only articles in English were reviewed. Summary sensitivity and specificity for antigen tests were generated using a random-effects model. RESULTS: Fourteen studies with 8624 participants were included. The meta-analysis for antigen testing generated a pooled sensitivity of 79% (95% CI, 66%-88%; 14 studies, 8624 patients) and a pooled specificity of 100% (95% CI, 99%-100%; 14 studies, 8624 patients). The subgroup analysis of studies that reported specimen collection within 7 days after symptom onset showed a pooled sensitivity of 95% (95% CI, 78%-99%; four studies, 1342 patients) and pooled specificity of 100% (95% CI, 97%-100%; four studies, 1342 patients). Regarding the applicability, the patient selection, index tests, and reference standards of studies in our meta-analysis matched the review title. CONCLUSION: Antigen tests have moderate sensitivity and high specificity for the detection of SARS-CoV-2. Antigen tests might have a higher sensitivity in detecting SARS-CoV-2 within 7 days after symptom onset. Based on our findings, antigen testing might be an effective method for identifying contagious individuals to block SARS-CoV-2 transmission.

Modifications of intravitreal injections in response to the COVID-19 pandemic.

The Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented disruption to the normal operation of the healthcare system. On a worldwide scale, hospitals suspended nonurgent surgeries and outpatient visits to downsize clinical loadings to redistribute manpower to counteract the pandemic's impact. So far, there is no evidence-based guideline defining a clear line between urgent and nonurgent indications of intravitreal injections (IVI). Herein, we aimed to summarize IVI algorithm modifications and discuss the patient prioritization according to medical needs in the hostile environment in the COVID crisis. Assessing current literature, we found that neovascular age-related macular degeneration is considered the utmost priority among conditions that require IVI. Other conditions assigned with a high priority include monocular or quasi-monocular patients (only one eye > 20/40), neovascular glaucoma, and new patients with significant vision loss. Although patients with central retinal vein occlusion and proliferative diabetic retinopathy are not advised to delay treatments, we found no consistent evidence that correlated with a worse outcome. Diabetic macular edema and branch retinal vein occlusion patients undertaking treatment delay should be regularly followed up every 2 to 3 months. Serving as the principle of management behind the algorithm modifications, the reduction of both patient visit and IVI therapy counts should be reckoned together with the risk of permanent visual loss and COVID infection.

The role of micronutrient and immunomodulation effect in the vaccine era of COVID-19.

Different dietary nutrients have distinct effects, including enhancing immune response activity and supporting mucous membrane integrity. These effects are critical in fighting against pathogenic agents, which cover coronavirus disease 2019 (COVID-19), the coronavirus disease that shuts down globally. Recent researches have shown that micronutrient deficiency is commonly associated with compromised immune responses, respiratory tract infections, or even susceptibility to COVID-19. The relationship between Vit A and infection is its role in mucosal epithelium integrity (skin and mucous membrane), the supplementation could be an option for assisted-treating the SARS-CoV-2 virus and a possible prevention of lung infection. Vit C/ascorbic acid stimulates oxygen radical scavenging activity of the skin and enhances epithelial barrier function. Ascorbic acid alone or with other natural compounds (baicalin and theaflavin) may inhibit the expression of angiotensin-converting enzyme II in human small alveolar epithelial cells and limited the entry of SARS-CoV-2. Vitamin D receptors can be expressed by immune cells, and different immune cells (macrophages, monocytes, dendritic cells, T cells, and B cells) can convert Vit D into its active form 1,25-(OH)2 D. Oral vitamin D intake can be a readily way to restrict the viral infection through downregulation of ACE2 receptor and to attenuate the disease severity by decreasing the frequency of cytokine storm and pulmonary pro-inflammatory response. Vit E supports T-cell mediated functions, optimization of Th1 response, and suppression of Th2 response. Vitamin E supplementation can lower the production of superoxides and may favors the antioxidants and benefit the progress of COVID-19 treatment. Zinc plays an essential role in both innate and adaptive immune systems and cytokine production, and Zinc-dependent viral enzymes to initiate the infectious process have proved the Zinc levels are directly associated with symptoms relieved of COVID-19. Iron is an essential component of enzymes involved in the activation of immune cells, lower iron levels predispose to severe symptoms of SARS-CoV-2, and monitoring the status can predict the disease severity and mortality. Selenium participates in the adaptive immune response by supporting antibody production and development. Deficiency can reduce antibody concentration, decreased cytotoxicity of NK cells, compromised cellular immunity, and an attenuated response to vaccination. The COVID-19 vaccines including three broad categories, protein-based vaccines, gene-based vaccines (mRNA vaccines and DNA vaccines), combination of gene and protein-based vaccines. Micronutrients are involved in immunity from the virus entering the human to innate immune response and adaptive immune response. Micronutrients are indispensable in immune response of vaccination.

Pandemic analysis of infection and death correlated with genomic open reading frame 10 mutation in severe acute respiratory syndrome coronavirus 2 victims.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues the pandemic spread of the coronavirus disease 2019 (COVID-19), over 60 million people confirmed infected and at least 1.8 million dead. One of the most known features of this RNA virus is its easiness to be mutated. In late 2020, almost no region of this SARS-CoV-2 genome can be found completely conserved within the original Wuhan coronavirus. Any information of the SARS-CoV-2 variants emerged through as time being will be evaluated for diagnosis, treatment, and prevention of COVID-19. METHODS: We extracted more than two million data of SARS-CoV-2 infected patients from the open COVID-19 dashboard. The sequences of the 38-amino acid putative open reading frame 10 (Orf10) protein within infected patients were gathered output through from National Center for Biotechnology Information and the mutation rates in each position were analyzed and presented in each month of 2020. The mutation rates of A8 and V30 within Orf10 are displayed in selected counties: United States, India, German, and Japan. RESULTS: The numbers of COVID-19 patients are correlated to the death numbers, but not with the death rates (stable and <3%). The amino acid positions locating at A8(F/G/L), I13, and V30(L) within the Orf10 sequence stay the highest mutation rate; N5, N25, and N36 rank at the lowest one. A8F expressed highly dominant in Japan (over 80%) and German (around 40%) coming to the end of 2020, but no significant finding in other countries. CONCLUSION: The results demonstrate via mutation analysis of Orf10 can be further combined with advanced tools such as molecular simulation, artificial intelligence, and biosensors that can practically revealed for protein interactions and thus to imply the authentic Orf10 function of SARS-CoV-2 in the future.

Clinical manifestation and disease progression in COVID-19 infection.

Coronavirus disease 2019 (COVID-19) is mainly an infectious disease of the respiratory system transmitted through air droplets, and pulmonary symptoms constitute main presentations of this disease. However, COVID-19 demonstrates a clinically diverse manifestation ranging from asymptomatic presentation to critically illness with severe pneumonia, acute respiratory distress syndrome, respiratory failure, or multiple organ failure. Accumulating evidences demonstrated that COVID-19 has extrapulmonary involvement, including neurological, smelling sensation, cardiovascular, digestive, hepatobiliary, renal, endocrinologic, dermatologic system, and others. Over a third of COVID-19 patients manifest a wide range of neurological symptoms involving the central/peripheral nervous system. Underlying cardiovascular comorbidities were associated with detrimental outcomes, meanwhile the occurrence of cardiovascular complications correlate to poor survival. Gastrointestinal symptoms frequently occur and have been associated with a longer period of illness. Impaired hepatic functions were associated with the severity of the disease. Higher rate of acute kidney injury was reported in critically ill patients with COVID-19. Endocrinologic presentations of COVID-19 include exacerbating hyperglycemia, euglycemic ketosis, and diabetic ketoacidosis. The most common cutaneous manifestation was acro-cutaneous (pernio or chilblain-like) lesions, and other skin lesions consist of maculopapular rash, vesicular lesions, livedoid/necrotic lesions, exanthematous rashes, and petechiae. This review article summarized the general clinical signs and symptoms, radiologic features, and disease manifestation with progression in patients with COVID-19.

Systematic review and meta-analysis of the effectiveness and safety of hydroxychloroquine in treating COVID-19 patients.

BACKGROUND: Since COVID-19 outbreak, hydroxychloroquine (HCQ) has been tested for effective therapies, and the relevant researches have shown controversial results. METHODS: Systematic review and meta-analysis were conducted after a thorough search of relevant studies from databases. Trials that have evaluated HCQ for COVID-19 treatment were recruited for statistical analysis with fixed- and random-effect models. RESULTS: Nine trials involving 4112 patients were included in present meta-analysis. It was seen that HCQ-azithromycin (HCQ-AZI) combination regimen increased the mortality rate in COVID-19 (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.63-3.36) patients; however, it also showed benefits associated with the viral clearance in patients (OR, 27.18; 95% CI, 1.29-574.32). HCQ-alone when used as a therapy in COVID-19 did not reveal significant changes in mortality rate, clinical progression, viral clearance, and cardiac QT prolongation. Subsequent subgroup analysis showed that HCQ treatment could decrease mortality rate and progression to severe illness in severely infected COVID-19 patients (OR, 0.27; 95% CI, 0.13-0.58). A lower risk of mortality rate was also noted in the stratified group of >14 days follow-up period (OR, 0.27; 95% CI, 0.13-0.58) compared to ≤14 days follow-up period group that conversely showed an increased mortality rate (OR, 2.09; 95% CI, 1.41-3.10). CONCLUSION: Our results indicated that HCQ-AZI combination treatment increased mortality rate in patients with COVID-19, but it also showed benefits associated with viral clearance in patients. HCQ-alone used for treatment has revealed benefits in decreasing the mortality rate among severely infected COVID-19 group and showed potential to be used for COVID-19 treatment in long-term follow-up period group. Accordingly, more rigorous, large-scale, and long follow-up period studies in patients with COVID-19 are needed.

Expression of Endogenous Angiotensin-Converting Enzyme 2 in Human Induced Pluripotent Stem Cell-Derived Retinal Organoids.

Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal organoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.

Highlight of severe acute respiratory syndrome coronavirus-2 vaccine development against COVID-19 pandemic.

The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has brought an unprecedented impact upon the global economy and public health. Although the SARS-CoV-2 virology has been gradually investigated, measures to combat this new threat in public health are still absent. To date, no certificated drug or vaccine has been developed for the treatment or prevention of coronavirus disease Extensive researches and international coordination has been conducted to rapidly develop novel vaccines against SARS-CoV-2 pandemic. Several major breakthroughs have been made through the identification of the genetic sequence and structural/non-structural proteins of SARS-CoV-2, which enabled the development of RNA-, DNA-based vaccines, subunit vaccines, and attenuated viral vaccines. In this review article, we present an overview of the recent advances of SARS-CoV-2 vaccines and the challenges that may be encountered in the development process, highlighting the advantages and disadvantages of these approaches that may help in effectively countering COVID-19.

A review of severe acute respiratory syndrome coronavirus 2 infection in the reproductive system.

An outbreak of pneumonia associated with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, China, in December 2019, and has been spread worldwide rapidly now. Over 5.3-million confirmed cases and 340,000 disease-associated deaths have been found till May 25, 2020. The potential pathophysiology for SARS-CoV-2 to affect the target is via the receptor, angiotensin-converting enzyme 2 (ACE2). ACE2 can be found in the respiratory, cardiovascular, gastrointestinal tract, urinary tract, and reproductive organs such as human ovaries and Leydig cells in the testis. This receptor plays a dominant role in the fertility function. Considering the crucial roles of testicular cells of the male reproductive system, increasing numbers of studies focus on the effects of SARS-CoV-2 on the testis. In this literature, we reviewed several studies to evaluate the relevance between SARS-CoV-2, ACE receptor, and female and male reproductive system and found that the risk of being attacked by SARS-CoV-2 is higher in males than in females. Since men infected with SARS-CoV-2 virus may have the risk of impaired reproductive performance, such as the orchitis and an elevated of luteinizing hormone (LH), and additionally, SARS-CoV-2 virus may be found in semen, although the latter is still debated, all suggest that we should pay much attention to sexual transmitted disease and male fertility after recovering from COVID-19.

Severe acute respiratory syndrome coronavirus-2 and the deduction effect of angiotensin-converting enzyme 2 in pregnancy.

The 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) is a pandemic disease worldwide. The spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is continuing at a rapid speed. Till May 4, 2020, there have been 3,407,747 confirmed cases and 238,198 deaths globally. The common symptoms in pregnant women are fever, cough, and dyspnea. Angiotensin-converting enzyme 2 (ACE2) has transient overexpression and increased activity during pregnancy, which is now confirmed as the receptor of SARS-CoV-2 and plays essential roles in human infection and transmission. There is no evidence that pregnant women are more susceptible to SARS-CoV-2. To date, there is no valid medication or vaccination. The immune suppression or modulation during pregnancy increases the risk of severe pneumonia. Remdesivir is an antiviral medication targeting ribonucleic acid (RNA) synthesis that has clinical improvement in the treatment of SARS-CoV-2. Chloroquine is controversial in its effectiveness and safety to treat SARS-CoV-2. Remdesivir is safe in pregnancy. Chloroquine has not been formally assigned to a pregnancy category by the Food and Drug Administration (FDA). The management strategy includes monitoring fetal heart rate and uterine contractions; early oxygenation if O2 saturation is less than 95%; empiric antibiotics for prevention of secondary infection; corticosteroid to treat maternal SARS-CoV-2 disease routinely is not suggested, only for fetal lung maturation in selected cases; and consideration of delivery is according to the obstetric indication, gestational age, and severity of the disease. During epidemics, delivery at 32-34 weeks is considered. The indication for the Cesarean section should be flexible to minimize the risk of infection during the delivery. The newborn should be in isolation ward immediately after birth; breastfeeding is not contraindicated but should avoid direct transmission infection.

Role of dipeptidyl peptidase-4 inhibitors in patients with diabetes infected with coronavirus-19.

The pandemic infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is widely increasing the patients affiliated with coronavirus disease 2019 (COVID-19) from last December of 2019. It is reported that the entry receptor of SARS-CoV-2 has been confirmed to be angiotensin-converting enzyme 2 (ACE2). Notably, whether the ACE-related inhibitors or drugs modulated ACE2 activity in affecting the viral activity and disease severity of SARS-CoV-2 is still an open question. Dipeptidyl peptidase-4 (DDP-4), a well-known anti-diabetic drug, has been widely used to control the glycemic condition in patients with diabetes. In this article, we are focusing on the impact of ACE inhibitors (ACEI) and DPP4 inhibitors used on SARS-CoV-2 activity and discussions about those drugs that may be related to infectious condition of COVID-19 diseases.

Care for Patients with Stroke During the COVID-19 Pandemic: Physical Therapy and Rehabilitation Suggestions for Preventing Secondary Stroke.

Infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the development of the novel 2019 coronavirus disease (COVID-19) and associated clinical symptoms, which typically presents as an upper respiratory syndrome such as pneumonia. Growing evidence indicates an increased prevalence of neurological involvement (e.g., in the form of stroke) during virus infection. COVID-19 has been suggested to be more than a lung infection because it affects the vasculature of the lungs and other organs and increases the risk of thrombosis. Patients with stroke are vulnerable to secondary events as a result not only of their poor vascular condition but also of their lack of access to rehabilitation resources. Herein, we review current knowledge regarding the pathophysiology of COVID-19, its possible association with neurological involvement, and current drug therapies. Suggestions are also offered regarding the potential for current neurorehabilitation therapies to be taught and practiced at home.

Pharmacological development of the potential adjuvant therapeutic agents against coronavirus disease 2019.

As the coronavirus disease 2019 (COVID-19, also called severe acute respiratory syndrome coronavirus-2) outbreak accelerates, vigorous and diverse efforts were made in developing treatment strategies. In addition to direct acting agents, increasing evidence showed some potential adjuvant therapies with promising efficacy against COVID-19. These therapies include immunomodulators (i.e. intravenous immunoglobulin, thymosin α-1, interleukin [IL]-6, tocilizumab, cyclosporine, thalidomide, fingolimod), Chinese medicines (i.e. glycyrrhizin, baicalin, Xuebijing), anti-vascular endothelial growth factors (bevacizumab), estrogen modulating drugs, statins, and nutritional supplements (i.e. vitamins A, B, C, D, E and zinc). This article reviewed the pharmacological development of potential adjuvants for COVID-19 treatment.

Highlight of Immune Pathogenic Response and Hematopathologic Effect in SARS-CoV, MERS-CoV, and SARS-Cov-2 Infection.

A sudden outbreak of COVID-19 caused by a novel coronavirus, SARS-CoV-2, in Wuhan, China in December 2019 quickly grew into a global pandemic, putting at risk not only the global healthcare system, but also the world economy. As the disease continues to spread rapidly, the development of prophylactic and therapeutic approaches is urgently required. Although some progress has been made in understanding the viral structure and invasion mechanism of coronaviruses that may cause severe cases of the syndrome, due to the limited understanding of the immune effects caused by SARS-CoV-2, it is difficult for us to prevent patients from developing acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF), the major complications of coronavirus infection. Therefore, any potential treatments should focus not only on direct killing of coronaviruses and prevention strategies by vaccine development, but also on keeping in check the acute immune/inflammatory responses, resulting in ARDS and PF. In addition, potential treatments currently under clinical trials focusing on killing coronaviruses or on developing vaccines preventing coronavirus infection largely ignore the host immune response. However, taking care of SARS-CoV-2 infected patients with ARDS and PF is considered to be the major difficulty. Therefore, further understanding of the host immune response to SARS-CoV-2 is extremely important for clinical resolution and saving medication cost. In addition to a breif overview of the structure, infection mechanism, and possible therapeutic approaches, we summarized and compared the hematopathologic effect and immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also discussed the indirect immune response caused by SARS and direct infection, replication, and destroying of immune cells by MERS-CoV. The molecular mechanisms of SARS-CoV and MERS-CoV infection-induced lymphopenia or cytokine storm may provide some hint toward fight against SARS-CoV-2, the novel coronavirus. This may provide guidance over using immune therapy as a combined treatment to prevent patients developing severe respiratory syndrome and largely reduce complications.

The pharmacological development of direct acting agents for emerging needed therapy against SARS-CoV-2

Recently, the SARS-CoV-2 was quickly identified as the causal pathogen leading to the outbreak of severe acute respiratory syndrome-like illness all over the world. As the SARS-CoV-2 infection pandemic proceeds, many efforts are being dedicated to the development of diverse treatment strategies. Increasing evidence showed potential therapeutic agents directly acting against SARS-CoV-2 virus, such as interferon, RNA-dependent RNA polymerase inhibitors, protease inhibitors, viral entry blockers, neuraminidase inhibitor, vaccine, antibody agent targeting the SARS-CoV-2 RNA genome, natural killer cells and nucleocytoplasmic trafficking inhibitor. To date, several direct anti-SARS-CoV-2 agents have demonstrated promising in vitro and clinical efficacy. This article reviews the current and future development of direct acting agents against SARS-CoV-2.