Different Laboratory Abnormalities in COVID-19 Patients with Hypertension or Diabetes

We reported recently that hypertension is a risk factor for severe cases of COVID-19, independent of age and other variables (Liu et al. 2020a). An important question is why patients with hypertension and diabetes yield poorer clinical outcomes than those without. Human pathogenic coronavirus SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as a receptor for viral cell entry. Since the levels of ACE2 are substantially increased in patients with hypertension or diabetes, who are treated with ACE inhibitors (ACEIs) and angiotensin Ⅱ type-Ⅰ receptor blockers (ARBs) (Ferrario et al. 2005), Fang and colleagues hypothesized that ACE2-stimulating drugs could potentially increase the risk of developing severe COVID-19 (Fang et al. 2020). This was not supported by a recent study led by Dr. Reynolds (Reynolds et al. 2020), whose analysis showed no positive association for ACEIs or ARBs for either the risk of SARS-CoV-2 infection or severe illness (Reynolds et al. 2020). What else might explain the poorer clinical outcomes of COVID-19 patients with hypertension or diabetes?To explore this question, we re-analysed the same cohort of 99 COVID-19 patients discharged from the general wards of Renmin Hospital of Wuhan University between 5 February 2020 and 14 March 2020 (Ethics approval No: WDRY2020-K124) (Liu et al. 2020a, b).     

Fish ACE2 is not susceptible to SARS-CoV-2

The ongoing pandemic of coronavirus disease 2019 (COVID-19) has reshaped our daily life and caused > 4 million deaths worldwide (https://covid19.who.int/). Although lockdown and vaccination have improved the situation in many countries, imported cases and sporadic outbreaks pose a constant stress to the prevention and control of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent responsible for COVID-19, has a positive-sense single-stranded RNA genome of 30 kb (Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, 2020). We and other groups have demonstrated that the SARS-CoV-2 could use the angiotensin-converting enzyme 2 (ACE2) as cell receptor, including orthologs of a broad range of animal species such as human, bats, ferrets, pigs, cats, and dogs (Hoffmann et al., 2020; Zhou et al., 2020; Liu et al., 2021). Although the evolutionary origin of SARS-CoV-2 can be linked to the discoveries of diverse coronaviruses related to SARS-CoV-2 in wild animals such as bats (Zhou et al., 2020; Wacharapluesadee et al., 2021) and pangolins (Liu et al., 2019; Lam et al., 2020), the direct origin of SARS-CoV-2 in humans remains unknown. In China, several sporadic outbreaks of COVID-19 in 2020 were linked to food in cold chain sold at trade markets, including salmon meat (http://www.nhc.gov.cn/xcs/yqtb/list_gzbd.shtml) (Yang et al., 2020). The detection of SARS-CoV-2 RNA on the surface of frozen meat for as long as 20 days has also been reported (Feng et al., 2021). A concern regarding the potential role of fish in SARS-CoV-2 transmission has also been raised. Therefore, we investigated the susceptibility of fish ACE2 to SARS-CoV-2.     

Genetic tracing of HCoV-19 for the re-emerging outbreak of COVID-19 in Beijing,China

The ongoing pandemic of coronavirus disease 2019(COVID-19)caused by a novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2,also named as 2019-nCoV or HCoV-19)poses an unprecedented threat to public health(Zhu et al.,2020;Wang et al.,2020;Jiang et al.,2020).The novel HCoV-19 virus has rapidly spread into multiple countries across the world since it was first reported in December 2019.The World Health Organization(WHO)declared COVID-19 as a pandemic on 11th March 2020.As of 4th July,over 10 million confirmed COVID-19 cases have been reported in over 200 countries/regions with more than 0.5 million deaths,including 85,287 documented cases and 4,648 deaths in China(WHO,2020a).     

Repurposing FDA-approved drugs for SARS-CoV-2 through an ELISA-based screening for the inhibition of RBD/ACE2 interaction

Dear Editor, The ongoing coronavirus disease 2019(COVID-19)global pandemic is caused by a novel coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which instigates severe and often fatal symptoms.As of September 4th,2020,more than 26 million cases of COVID-19 and almost 900,000 deaths have been reported to WHO.Based on Kissler and colleagues'modeled projections of future viral transmission scenarios,a resurgence in SARS-CoV-2 could occur over the next five years(Kissler et al.,2020).Research and clinical trials are underway to develop vacci-nes and treatments for COVID-19,but there are currently no specific vaccines or treatments for COVID-19(www.who.int),and therapeutic and prophylactic interventions are urgently needed to combat the outbreak of SARS-CoV-2.Of partic-ular importance is the identification of drugs which are effective,less-intrusive,most socioeconomic,and ready-to-use.     

Old Weapon for New Enemy: Drug Repurposing for Treatment of Newly Emerging Viral Diseases

正Emerging and re-emerging viral diseases are a public health concern for the whole world and pose a major threat to human health and life. In last decades, numerous major outbreaks of emerging and re-emerging viral diseases with gross public concern were recorded in different regions,including Ebola in western Africa, Zika in South America,     

Clinical characteristics and co-infections of 354 hospitalized patients with COVID-19 in Wuhan,China: a retrospective cohort study

From December 2019, a novel coronavirus, SARS-CoV-2, caused an outbreak of pneumonia in Wuhan city and rapidly spread throughout China and globally. However, the clinical characteristics and co-infection with other respiratory pathogens of patients with COVID-19 and the factors associated with severity of COVID-19 are still limited. In this retrospective cohort study, we included 354 inpatients with COVID-19 admitted to Renmin Hospital of Wuhan University from February 4, 2020 to February 28, 2020. We found levels of interleukin-6, interleukin-10, C-reactive protein, D-dimer, white blood cell count and neutrophil count were clearly elevated in males and critical cases compared with females and severe and mild cases, respectively. However, lymphopenia was more severe in males than females and levels of tumor necrosis factor alpha were reduced significantly in critical cases than severe and mild cases. 23.5% of severe cases and 24.4% of critical cases were co-infected with other respiratory pathogens. Additionally, stepwise multivariable regression analysis suggested that co-infection, lymphocyte count and levels of D-dimer were associated with severity of COVID-19.These findings provide crucial clues for further identification of the mechanisms, characteristics and treatments of patients with COVID-19.     

Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine

Dear Editor, The rapid emergence and persistence of the pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has had enormous impacts on global health and the economy.Effective vaccines against SARS-CoV-2 are urgently needed to control the coronavirus disease 2019(COVID-19) pandemic,and multiple vaccines have been found to be efficacious in preventing symptomatic COVID-19(Polack et al.,2020;Wu et al.,2020;Jones and Roy,2021).We have developed a traditional beta-propiolactone-inacti-vated aluminum hydroxide-adjuvanted whole-virion SARS-CoV-2 vaccine (BBIBP-CorV),which elicited protective immune responses in clinical trials (Wang et al.,2020;Xia et al.,2021).The vaccine has been granted conditional approvals or emergency use authorizations (EUAs) in China and other countries.     

IL-15 immunotherapy is a viable strategy for COVID-19

Coronavirus disease 2019 (COVID-19) is a pulmonary inflammatory disease induced by a newly recognized coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection was detected for the first time in the city of Wuhan in China and spread all over the world at the beginning of 2020. Several millions of people have been infected with SARS-CoV-2, and almost 382,867 human deaths worldwide have been reported so far. Notably, there has been no specific, clinically approved vaccine or anti-viral treatment strategy for COVID-19. Herein, we review COVID-19, the viral replication, and its effect on promoting pulmonary fibro-inflammation via immune cell-mediated cytokine storms in humans. Several clinical trials are currently ongoing for anti-viral drugs, vaccines, and neutralizing antibodies against COVID-19. Viral clearance is the result of effective innate and adaptive immune responses. The pivotal role of interleukin (IL)-15 in viral clearance involves maintaining the balance of induced inflammatory cytokines and the homeostatic responses of natural killer and CD8⁺ T cells. This review presents supporting evidence of the impact of IL-15 immunotherapy on COVID-19.     

An integrated rapid nucleic acid detection assay based on recombinant polymerase amplification for SARS-CoV-2

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that causes the outbreak of coronavirus disease 2019 (COVID-19) (Li et al., 2020a). Viral nucleic acid testing is the standard method for the laboratory diagnosis of COVID-19 (Wu et al., 2020a; Zhu et al., 2020). Currently, a variety of qPCR-based detection kits are used for laboratory-based detection and confirmation of SARS-CoV-2 infection (Corman et al., 2020; Hussein et al., 2020; Ruhan et al., 2020; Veyer et al., 2020). Conventional qPCR involves virus inactivation, nucleic acid extraction, and qPCR amplification procedures. Therefore, the process is complicated, which usually takes longer than 2 h, and requires biosafety laboratories and professional staff. Thus, qPCR is not suitable for use in field or medical units. To reduce the operation steps, automatic integrated qPCR detection systems that combine nucleic acid extraction and qPCR amplification in a sealed cartridge were developed to detect viruses in clinical samples (Li et al., 2020b). However, the detection time is still longer than 1 h. Therefore, rapid nucleic acid detection systems are needed to further improve the detection efficiency.     

Re-detectable positive SARS-CoV-2 RNA tests in patients who recovered from COVID-19 with intestinal infection

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCoV-2),a novel coronavirus that causes Coronavirus Disease 2019(COVID-19)(Yang and Wang,2020),has spread to more than 200 countries and infected more than 9,000,000 people as of Jun 2020.Tens of thousands of patients with COVID-19 have recovered and been discharged from hospital.However,there are reports of recovered patients who subsequently tested positive for SARSCoV-2 after discharge(re-detectable positive,RP)(An et al.,2020;Lan et al.,2020),and this has led to increasing focus on the mechanism(s)underlying RP.     

Cytokine storm intervention in the early stages of COVID-19 pneumonia

Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30^th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.     

SARS-CoV-2 Serological Survey of Cats in China before and after the Pandemic

The high percentage of seropositivity of cats in Wuhan, the epicentre of the SARS-CoV-2 epidemic, could be due to the large number of infected human cases (more than 14 folds than that in other cities) (Table 1) where cats may have been more frequently exposed to SARS-CoV-2 patients or contaminated environment. As yet, SARS-CoV-2 serological prevalence of cats in other Chinese cities remains unknown. Therefore, a serological survey including more cities with numbers of SARS-CoV-2 human cases in China will be valuable for elucidating the role of cats in transmission of the viruses and relieve public concerns. In this study, 630 cat serum samples collected before November 2019 and 423 cat serum samples collected during SARS-CoV-2 outbreak (from February 2020 to April 2020) in 20 cities in China for detecting the prevalence of SARS-CoV-2 specific antibodies.     

Severe Acute Respiratory Syndrome Coronavirus 2: Manifestations of Disease and Approaches to Treatment and Prevention in Humans

The coronavirus disease 2019 (COVID-19) pandemic was caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus has challenged civilization and modern science in ways that few infectious diseases and natural disasters have previously, causing globally significant human morbidity and mortality and triggering economic downturns across financial markets that will be dealt with for generations. Despite this, the pandemic has also brought an opportunity for humanity to come together and participate in a shared scientific investigation. Clinically, SARS-CoV-2 is associated with lower mortality rates than other recently emerged coronaviruses, such as SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV). However, SARS-CoV-2 exhibits efficient human-to-human spread, with transmission often occurring before symptom recognition; this feature averts containment strategies that had worked previously for SARS-CoV and MERS-CoV. Severe COVID-19 disease is characterized by dysregulated inflammatory responses associated with pulmonary congestion and intravascular coagulopathy leading to pneumonia, vascular insults, and multiorgan disease. Approaches to treatment have combined supportive care with antivirals, such as remdesivir, with immunomodulatory medications, including corticosteroids and cytokine-blocking antibody therapies; these treatments have advanced rapidly through clinical trials. Innovative approaches to vaccine development have facilitated rapid advances in design, testing, and distribution. Much remains to be learned about SARS-CoV-2 and COVID-19, and further biomedical research is necessary, including comparative medicine studies in animal models. This overview of COVID-19 in humans will highlight important aspects of disease, relevant pathophysiology, underlying immunology, and therapeutics that have been developed to date.

In December 2019, a cluster of cases of pneumonia without a clear etiology occurred in Wuhan, China. With remarkable speed and efficiency, the etiology of this illness was soon identified as a novel coronavirus; the complete viral genome was sequenced and published on January 10, 2020.¹⁸² These events introduced the world to coronavirus disease 2019 (COVID-19). The disease, now known to be caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has developed into the most significant pandemic of recent times. In less than a year since the virus was first recognized, multiple candidate vaccines were developed worldwide, and some of them rapidly progressed to clinical trials and widespread administration. As the pandemic continues, a number of sequence variants of the virus have emerged around the world. This continued viral evolution highlights the need for continued biomedical research to facilitate understanding of the pathogenesis of COVID-19, seeking innovative therapeutic and preventative strategies for the current and possibly future pandemics. This article will review aspects of SARS-CoV-2 infection of humans and COVID-19, focusing on important aspects of clinical disease, pathophysiology, immunology, and the development of therapeutic and preventative measures to provide context for discussion of the animal models used to study SARS-CoV-2 and COVID-19.     

SARS-CoV-2 pathophysiology and assessment of coronaviruses in CNS diseases with a focus on therapeutic targets

The novel Coronavirus disease of 2019 (nCOV-19) is a viral outbreak noted first in Wuhan, China. This disease is caused by Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2. In the past, other members of the coronavirus family, such as SARS and Middle East Respiratory Syndrome (MERS), have made an impact in China and the Arabian peninsula respectively. Both SARS and COVID-19 share similar symptoms such as fever, cough, and difficulty in breathing that can become fatal in later stages. However, SARS and MERS infections were epidemic diseases constrained to limited regions. By March 2020 the SARS-CoV-2 had spread across the globe and on March 11th, 2020 the World Health Organization (WHO) declared COVID-19 as pandemic disease. In severe SARS-CoV-2 infection, many patients succumbed to pneumonia. Higher rates of deaths were seen in older patients who had co-morbidities such as diabetes mellitus, hypertension, cardiovascular disease (CVD), and dementia. In this review paper, we discuss the effect of SARS-CoV-2 on CNS diseases, such as Alzheimer's-like dementia, and diabetes mellitus. We also focus on the virus genome, pathophysiology, theranostics, and autophagy mechanisms. We will assess the multiorgan failure reported in advanced stages of SARS-CoV-2 infection. Our paper will provide mechanistic clues and therapeutic targets for physicians and investigators to combat COVID-19.     

The NLRP3 inflammasome and COVID-19: Activation,pathogenesis and therapeutic strategies

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical presentations, ranging from asymptomatic cases to severe pneumonia or even death. In severe COVID-19 cases, an increased level of proinflammatory cytokines has been observed in the bloodstream, forming the so-called “cytokine storm”. Generally, nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation intensely induces cytokine production as an inflammatory response to viral infection. Therefore, the NLRP3 inflammasome can be a potential target for the treatment of COVID-19. Hence, this review first introduces the canonical NLRP3 inflammasome activation pathway. Second, we review the cellular/molecular mechanisms of NLRP3 inflammasome activation by SARS-CoV-2 infection (e.g., viroporins, ion flux and the complement cascade). Furthermore, we describe the involvement of the NLRP3 inflammasome in the pathogenesis of COVID-19 (e.g., cytokine storm, respiratory manifestations, cardiovascular comorbidity and neurological symptoms). Finally, we also propose several promising inhibitors targeting the NLRP3 inflammasome, cytokine products and neutrophils to provide novel therapeutic strategies for COVID-19.     

Seroprevalence of COVID-19 in Riyadh city during the early increase of COVID-19 infections in Saudi Arabia,June 2020

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) emerged in December 2019 and caused a global pandemic of the Coronavirus Disease 2019 (COVID-19). More than 170 million cases have been reported worldwide with mortality rate of 1–3%. The detection of SARS-CoV-2 by molecular testing is limited to acute infections, therefore serological studies provide a better estimation of the virus spread in a population. This study aims to evaluate the seroprevalence of SARS-CoV-2 in the major city of Riyadh, Saudi Arabia during the sharp increase of the pandemic, in June 2020. Serum samples from non-COVID patients (n = 432), patients visiting hospitals for other complications and confirmed negative for COVID-19, and healthy blood donors (n = 350) were collected and evaluated using an in-house enzyme-linked immunosorbent assay (ELISA). The overall percentage of positive samples was 7.80% in the combined two populations (n = 782). The seroprevalence was lower in the blood donors (6%) than non-COVID-19 patients (9.25%), p = 0.0004. This seroprevalence rate is higher than the documented cases, indicating asymptomatic or mild unreported COVID-19 infections in these two populations. This warrants further national sero-surveys and highlights the importance of real-time serological surveillance during pandemics.     

In silico investigation of ACE2 and the main protease of SARS-CoV-2 with phytochemicals from Myristica fragrans (Houtt.) for the discovery of a novel COVID-19 drug

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is a new coronavirus strain that was first reported in December 2019 in Wuhan, China. A specific treatment for COVID-19 has yet to be identified. Potential therapeutic targets include SARS-CoV-2 main protease (Mpro) and the SARS-CoV-2 spike-ACE2 interaction. Molecular docking, molecular dynamics (MD), solvent screening for the extraction of the specified compounds, and prediction of the drug properties of certain molecules were the methods used in this study to investigate compounds from the medicinal plant Myristica fragrans, which is one of twelve herbs in Prasachandaeng remedy (PSD). ArgusLab, AutoDock Vina, and AutoDock were used to perform docking tasks. The examined ligands were compared with panduratin A as a standard (Kanjanasirirat et al., 2020), which is a promising medicinal plant molecule for the treatment of COVID-19. Molecular docking revealed that malabaricones B and C and licarins A, B and C bound to SARS-CoV-2/ACE2 and SARS-CoV-2 Mpro with low binding energies compared to that of the standard ligand. Furthermore, appropriate solvent usage is important. Acetone was selected by COSMOquick software for compound extraction in this investigation because it can extract large amounts of all five of the abovementioned M. fragrans compounds. Furthermore, the drug-like properties of these compounds were studied utilizing the Lipinski, Veber, and Ghose criteria. The results revealed that these M. fragrans compounds have potential as effective medicines to combat the COVID-19 pandemic. However, to assess the therapeutic potential of these ligands, additional research is needed, which will use our findings as a foundation.     

COVID-19-related coagulopathy: A review of pathophysiology and pharmaceutical management

December 2019 will never be forgotten in the history of medicine when an outbreak of pneumonia of unknown etiology in Wuhan, China sooner or later prompted the World Health Organization to issue a public health warning emergency. This is not the first nor will it be the last time that a member of β-coronaviruses (CoVs) is waging a full-scale war against human health. Notwithstanding the fact that pneumonia is the primary symptom of the novel coronavirus (2019nCoV; designated as SARS-CoV-2), the emergence of severe disease mainly due to the injury of nonpulmonary organs at the shadow of coagulopathy leaves no choice, in some cases, rather than a dreadful death. Multiple casual factors such as inflammation, endothelial dysfunction, platelet and complement activation, renin-angiotensin-aldosterone system derangement, and hypoxemia play a major role in the pathogenesis of coagulopathy in coronavirus disease 2019 (COVID-19) patients. Due to the undeniable role of coagulation dysfunction in the initiation of several complications, assessment of coagulation parameters and the platelet count would be beneficial in early diagnosis and also timely prediction of disease severity. Although low-molecular-weight heparin is considered as the first-line of treatment in COVID-19-associated coagulopathy, several possible therapeutic options have also been proposed for better management of the disease. In conclusion, this review would help us to gain insight into the pathogenesis, clinical manifestation, and laboratory findings associated with COVID-19 coagulopathy and would summarize management strategies to alleviate coagulopathy-related complications.