Designing therapeutic strategies to combat severe acute respiratory syndrome coronavirus-2 disease: COVID-19.
TL;DR: The current review elucidates the disease pathology and summarizes the possible therapeutic options to battle against COVID‐19 on the basis of current state of understanding about SARS‐ CoV‐2 pathogenic pathways and knowledge gained from previous SARS and MERS‐CoV epidemics.
Abstract: A highly contagious coronavirus disease COVID-19 caused by a recently identified severe acute respiratory syndrome CoV-2 (SARS-CoV-2) initially detected in Wuhan, China has spread worldwide and become a major health crisis in the absence of specific vaccine or antiviral drugs. SARS-CoV-2 infection has resulted in overwhelming number of reported deaths. Unfortunately it is still spreading uncontrollably despite implementing stringent protective measures. Rapid development of effective therapeutic strategies for treatment and prevention of infection is crucially required. Although genomic characterization has assisted in unfolding various aspects of SARS-CoV-2 but development of specific antiviral drugs and vaccine against COVID-19 is still a worldwide challenge. Understanding the disease pathological course underlying the clinical manifestations of COVID-19 is imperative to identify the vital targets for drug development. SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) receptor to enter the host cell and primarily target type II alveolar cells. COVID-19 disease progression is associated with distressed immune functions and hyper active inflammatory system leading to development of cytokine storm which is a vital factor involved in disease advancement. The current review elucidates the disease pathology and summarizes the possible therapeutic options to battle against COVID-19 on the basis of current state of understanding about SARS-CoV-2 pathogenic pathways and knowledge gained from previous SARS and MERS-CoV epidemics. Therapeutic strategies to treat and prevent infection as well as to suppress the disease progression to reduce severity and mortality rate is discussed. Drug candidates currently under consideration and undergoing clinical trials for COVID-19 treatment are highlighted.
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01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
4,408 citations
19 Aug 2011
318 citations
TL;DR: Wang et al. as mentioned in this paper summarized the main phytochemical components of LJF and reviewed its updated pharmacological effects, including inhibition of inflammation, pyrexia, viruses, and bacteria, immunoregulation, and protection of the liver, nervous system, and heart.
11 citations
TL;DR: Wang et al. as discussed by the authors evaluated the effectiveness and safety of olfactory training for COVID-19 patients with smell disorders, and the conclusion of their study will provide evidence to prove the effectiveness of Olfactory Training.
10 citations
TL;DR: In this paper , the authors addressed the severity and risk factors of hypercytokinemia in COVID-19 patients, with special emphasis on prospective immunomodulatory therapies.
Abstract: The year 2020 is characterised by the COVID-19 pandemic that has quelled more than half a million lives in recent months. We are still coping with the negative repercussions of COVID-19 pandemic in 2021, in which the 2nd wave in India resulted in a high fatality rate. Regardless of emergency vaccine approvals and subsequent meteoric global vaccination drives in some countries, hospitalisations for COVID-19 will continue to occur due to the propensity of mutation in SARS-CoV-2 virus. The immune response plays a vital role in the control and resolution of infectious diseases. However, an impaired immune response is responsible for the severity of the respiratory distress in many diseases. The severe COVID-19 infection persuaded cytokine storm that has been linked with acute respiratory distress syndrome (ARDS), culminates into vital organ failures and eventual death. Thus, safe and effective therapeutics to treat hospitalised patients remains a significant unmet clinical need. In that state, any clue of possible treatments, which save patients life, can be treasured for this time point. Many cohorts and clinical trial studies demonstrated that timely administration of immunomodulatory drugs on severe COVID-19 patients may mitigate the disease severity, hospital stay and mortality. This article addresses the severity and risk factors of hypercytokinemia in COVID-19 patients, with special emphasis on prospective immunomodulatory therapies.
7 citations
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TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
36,578 citations
"Designing therapeutic strategies to..." refers background in this paper
...Tumor necrosis factor-α a key player in immune activation and inflammation principally released from activated macrophages is found elevated in critically ill COVID-19 patients (Huang et al., 2020)....
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...…may also develop acute respiratory distress syndrome (ARDS), respiratory failure, acute cardiac injury, coagulation abnormalities, disturbed immune system causing amplified cytokines release, and multiple organ failure resulting in death (Chen et al., 2020; Huang et al., 2020; Wang et al., 2020)....
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...…antibody Tumor necrosis factor (TNF) α inhibition Inhibits tumor necrosis factor (TNF) α and prevent TNF dependent cytokine cascade and tissue damage Huang et al. (2020) Recombinant human soluble ACE2 (rhACE2) RAS modifier ACE2 enhancement Restore renin angiotensin system…...
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...Extensive laboratory test findings comprise higher leucocyte count, increased erythrocyte sedimentation rate (ESR), elevated C-reactine protein (CRP), creatinine kinase, lactate dehydrogenase, increased thrombogenic biomarkers D-dimer, and prolonged prothrombin time (Huang et al., 2020)....
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...Ground-glass opacification with or without consolidative abnormalities is revealed as hallmark of COVID-19 infection in Chest computed tomography (CT) (Huang et al., 2020)....
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TL;DR: Wang et al. as discussed by the authors used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death, including older age, high SOFA score and d-dimer greater than 1 μg/mL.
20,189 citations
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Abstract: Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1–4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5–7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV. Characterization of full-length genome sequences from patients infected with a new coronavirus (2019-nCoV) shows that the sequences are nearly identical and indicates that the virus is related to a bat coronavirus.
16,857 citations
"Designing therapeutic strategies to..." refers background or methods in this paper
...Several independent retrospective studies have assessed the risk factors associated with disease severity and stipulated older population with immune-compromised/co-morbid conditions as more vulnerable targets (Wang et al., 2020; Zhou et al., 2020a, b)....
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...…utilize the same entry portal as used by SARS-CoV (severe acute respiratory syndrome coronavirus), type 1 transmembrane angiotensin-converting enzyme 2 (ACE2) receptor to enter the host cell through fusion between viral and cellular membrane assisted by host cell proteases (Zhou et al., 2020a, b)....
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TL;DR: The epidemiological and clinical characteristics of novel coronavirus (2019-nCoV)-infected pneumonia in Wuhan, China, and hospital-associated transmission as the presumed mechanism of infection for affected health professionals and hospitalized patients are described.
Abstract: Importance In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
16,635 citations
"Designing therapeutic strategies to..." refers background in this paper
...Several independent retrospective studies have assessed the risk factors associated with disease severity and stipulated older population with immune-compromised/co-morbid conditions as more vulnerable targets (Wang et al., 2020; Zhou et al., 2020a, b)....
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...…may also develop acute respiratory distress syndrome (ARDS), respiratory failure, acute cardiac injury, coagulation abnormalities, disturbed immune system causing amplified cytokines release, and multiple organ failure resulting in death (Chen et al., 2020; Huang et al., 2020; Wang et al., 2020)....
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...Email: rh.suman@gmail.com A highly contagious coronavirus disease COVID-19 caused by a recently identified severe acute respiratory syndrome CoV-2 (SARS-CoV-2) initially detected in Wuhan, China has spread worldwide and become a major health crisis in the absence of spe- cific vaccine or antiviral drugs....
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...COVID 19 is a highly contagious respiratory tract infection caused by recently identified severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) originated from Wuhan, China (Wang et al., 2020)....
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...Recently remdesvir revealed inhibitory effects (EC90 of 1.76 μM) against SARS-CoV-2 in an in vitro cell culture study (Wang et al., 2020)....
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TL;DR: Characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia, and further investigation is needed to explore the applicability of the Mu LBSTA scores in predicting the risk of mortality in 2019-nCoV infection.
16,282 citations