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SARS-CoV-2 (COVID-19) spreads and develops quickly worldwide as a new global crisis which has left deep socio-economic damage and massive human mortality. This virus accounts for the ongoing outbreak and forces an urgent need to improve antiviral therapeutics and targeted diagnosing tools. Researchers have been working to find a new drug to combat the virus since the outbreak started in late 2019, but there are currently no successful drugs to control the SARS-CoV-2, which makes the situation riskier. Very recently, new variant of SARS-CoV-2 is identified in many countries which make the situation very critical. No successful treatment has yet been shown although enormous international commitment to combat this pandemic and the start of different clinical trials. Nanomedicine has outstanding potential to solve several specific health issues, like viruses, which are regarded a significant medical issue. In this review, we presented an up-to-date drug design strategy against SARS-CoV-2, including the development of novel drugs and repurposed product potentials were useful, and successful drugs discovery is a constant requirement. The use of nanomaterials in treatment against SARS-CoV-2 and their use as carriers for the transport of the most frequently used antiviral therapeutics are discussed systematically here. We also addressed the possibilities of practical applications of nanoparticles to give the status of COVID-19 antiviral systems. [ABSTRACT FROM AUTHOR]

Background: Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection.Methods: CONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting patients are randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP is collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at day 30. Secondary outcomes include ventilator-free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α = 0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n = 600).Discussion: This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titres and neutralization assays for donor qualification.Trial Registration: Clinicaltrials.gov NCT04348656 . Registered on 16 April 2020. [ABSTRACT FROM AUTHOR]

Introduction: Corona virus 2019 was first isolated in 1960. Middle East Respiratory Syndrome virus (MERS) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) also belongs to Corona viridae family. Human Coronavirus causes fever, cough, fatigue, respiratory infection and abdominal symptoms. This virus has a strong affinity to human respiratory receptors and transmits rapidly. Since the virus has spread around the world and has acquired features of emergency, WHO declared it as a pandemic in March 2020. Aim: To study the clinical, haematological, biochemical findings and significance of co-morbidities amongst COVID-19 positive survivors and nonsurvivors. Materials and Methods: A retrospective cohort study was done at Chattrapati Shivaji Subharti Hospital (CSSH), Meerut, Uttar Pradesh, a level 3 COVID-19 Hospital from mid-June to end of August 2020 including 140 COVID-19 positive patients selected randomly. Patients were categorised into asymptomatic and symptomatic. Symptomatic were further divided into survivors and nonsurvivors. Haematological and biochemical parameters were analysed amongst survivors and nonsurvivors, with calculation of significant p-value. Results: Out of 37/140 patients (26%) were asymptomatic and 103/140 (74%) symptomatic. Amongst symptomatic, survivors were 78/140 (56%) and nonsurvivors were 25/140 (18%) of total positive patients. Out of 37/140 (26%) asymptomatic patients, majority were in the age group 21-30 years 14/140 (10%) with female preponderance 10/140 (7.1%). Out of 78/140 (56%) survivors, majority were in 51 to 60 years age group, with male predominance17/140 (18.6%). Amongst 25/140 (18%) nonsurvivors most common affected age group was 51 to 60 years 10/140 (7.1%). Most common symptoms in survivors was cough (51/78 patients; 65%) and fever (35/78 patients; 45%). In Nonsurvivors, pneumonia was seen in 100% (25/25) patients. Out of 23/25 (92%) patients presented with fever, 19/25 (76%) had breathlessness, 16/25 (64%) had myalgia, 9/25 (36%) had cough, 5/25 (20%) presented with vomiting or pain in abdomen. Amongst nonsurvivors, Total Leucocyte Count (TLC), Absolute Neutrophil Count (ANC), Neutrophil Lymphocyte Ratio (NLR), urea, serum creatinine, serum bilirubin, Aspartate Amino Transferase (AST) and Alanine Amino Transferase (ALT) were significantly raised as compared to survivors (p<0.01); meanwhile platelet count and Platelet Lymphocyte Ratio (PLR) in nonsurvivors was significantly lower than survivors (p<0.01). Most common comorbidity was diabetes in 12/25 (48%) and hypertension in 6/25 (24%) among nonsurvivors. Conclusion: COVID-19 infection more likely affects older men with co-morbidities like diabetes mellitus and hypertension and can rapidly progress to pneumonia, Acute Respiratory Distress Syndrome (ARDS) and septic shock. Certain haematological and biological parameters have been found to be in concordance with increased mortality which can be reduced by early identification of these parameters. [ABSTRACT FROM AUTHOR]

Coronavirus Disease 2019 (COVID-19) has been classified as a global threat, affecting millions of people and killing thousands. It is caused by the SARS-CoV-2 virus, which emerged at the end of 2019 in Wuhan, China, quickly spreading worldwide. COVID-19 is a disease with symptoms that range from fever and breathing difficulty to acute respiratory distress and death, critically affecting older patients and people with previous comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and mainly spreads through the respiratory tract, which it then uses to reach several organs. The immune system of infected patients has been demonstrated to suffer important alterations, such as lymphopenia, exhausted lymphocytes, excessive amounts of inflammatory monocytes and macrophages, especially in the lungs, and cytokine storms, which may contribute to its severity and difficulty of establishing an effective treatment. Even though no specific treatment is currently available, several studies have been investigating potential therapeutic strategies, including the use of previously approved drugs and immunotherapy. In this context, this review addresses the interaction between SARS-CoV-2 and the patient's host immune system during infection, in addition to discussing the main immunopathological mechanisms involved in the development of the disease and potential new therapeutic approaches. [ABSTRACT FROM AUTHOR]

In December 2019, an outbreak of illness caused by a novel coronavirus (2019-nCoV, subsequently renamed SARS-CoV-2) was reported in Wuhan, China. Coronavirus disease 2019 (COVID-19) quickly spread worldwide to become a pandemic. Typical manifestations of COVID-19 include fever, dry cough, fatigue, and respiratory distress. In addition, both the central and peripheral nervous system can be affected by SARS-CoV-2 infection. These neurological changes may be caused by viral neurotropism, by a hyperinflammatory and hypercoagulative state, or even by mechanical ventilation-associated impairment. Hypoxia, endothelial cell damage, and the different impacts of different ventilatory strategies may all lead to increased stress and strain, potentially exacerbating the inflammatory response and leading to a complex interaction between the lungs and the brain. To date, no studies have taken into consideration the possible secondary effect of mechanical ventilation on brain recovery and outcomes. The aim of our review is to provide an updated overview of the potential pathogenic mechanisms of neurological manifestations in COVID-19, discuss the physiological issues related to brain-lung interactions, and propose strategies for optimization of respiratory support in critically ill patients with SARS-CoV-2 pneumonia. [ABSTRACT FROM AUTHOR]

After the 1918 flu pandemic, the world is again facing a similar situation. However, the advancement in medical science has made it possible to identify that the novel infectious agent is from the coronavirus family. Rapid genome sequencing by various groups helped in identifying the structure and function of the virus, its immunogenicity in diverse populations, and potential preventive measures. Coronavirus attacks the respiratory system, causing pneumonia and lymphopenia in infected individuals. Viral components like spike and nucleocapsid proteins trigger an immune response in the host to eliminate the virus. These viral antigens can be either recognized by the B cells or presented by MHC complexes to the T cells, resulting in antibody production, increased cytokine secretion, and cytolytic activity in the acute phase of infection. Genetic polymorphism in MHC enables it to present some of the T cell epitopes very well over the other MHC alleles. The association of MHC alleles and its downregulated expression has been correlated with disease severity against influenza and coronaviruses. Studies have reported that infected individuals can, after recovery, induce strong protective responses by generating a memory T-cell pool against SARS-CoV and MERS-CoV. These memory T cells were not persistent in the long term and, upon reactivation, caused local damage due to cross-reactivity. So far, the reports suggest that SARS-CoV-2, which is highly contagious, shows related symptoms in three different stages and develops an exhaustive T-cell pool at higher loads of viral infection. As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. A classical immunotherapy of convalescent plasma transfusion from recovered patients has also been initiated for the neutralization of viremia in terminally ill COVID-19 patients. Due to the limitations of plasma transfusion, researchers are now focusing on developing neutralizing antibodies against virus particles along with immuno-modulation of cytokines like IL-6, Type I interferons (IFNs), and TNF-α that could help in combating the infection. This review highlights the similarities of the coronaviruses that caused SARS and MERS to the novel SARS-CoV-2 in relation to their pathogenicity and immunogenicity and also focuses on various treatment strategies that could be employed for curing COVID-19. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome (SARS) has been recognized as a new human infectious disease caused by a novel coronavirus (SARS-CoV). Hematological changes in patients with SARS were common, including notably lymphopenia and thrombocytopenia. While the former is the result of decreases in CD4+ or CD8+ T-lymphocytes related to the onset of disease or use of glucocorticoids, the latter may involve a number of potential mechanisms. Although the development of autoimmune antibodies or immune complexes triggered by viral infection may play a significant role in inducing thrombocytopenia, SARS-CoV may also directly infect hematopoietic stem/progenitor cells, megakaryocytes and platelets inducing their growth inhibition and apoptosis. Moreover, the increased consumption of platelets and/or the decreased production of platelets in the damaged lungs are a potential alternative mechanism that can contribute to thrombocytopenia in severe critical pulmonary conditions, which has been rarely revealed and will be discussed. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has strengthened the interest in the biological mechanisms underlying the complex interplay between infectious agents and the human host. The spectrum of phenotypes associated with the SARS-CoV-2 infection, ranging from the absence of symptoms to severe systemic complications, raised the question as to what extent the variable response to coronaviruses (CoVs) is influenced by the variability of the hosts' genetic background. To explore the current knowledge about this question, we designed a systematic review encompassing the scientific literature published from Jan. 2003 to June 2020, to include studies on the contemporary outbreaks caused by SARS-CoV-1, MERS-CoV and SARS-CoV-2 (namely SARS, MERS and COVID-19 diseases). Studies were eligible if human genetic variants were tested as predictors of clinical phenotypes. An ad hoc protocol for the rapid review process was designed according to the PRISMA paradigm and registered at the PROSPERO database (ID: CRD42020180860). The systematic workflow provided 32 articles eligible for data abstraction (28 on SARS, 1 on MERS, 3 on COVID-19) reporting data on 26 discovery cohorts. Most studies considered the definite clinical diagnosis as the primary outcome, variably coupled with other outcomes (severity was the most frequently analysed). Ten studies analysed HLA haplotypes (1 in patients with COVID-19) and did not provide consistent signals of association with disease-associated phenotypes. Out of 22 eligible articles that investigated candidate genes (2 as associated with COVID-19), the top-ranked genes in the number of studies were ACE2, CLEC4M (L-SIGN), MBL, MxA (n = 3), ACE, CD209, FCER2, OAS-1, TLR4, TNF-α (n = 2). Only variants in MBL and MxA were found as possibly implicated in CoV-associated phenotypes in at least two studies. The number of studies for each predictor was insufficient to conduct meta-analyses. Studies collecting large cohorts from different ancestries are needed to further elucidate the role of host genetic variants in determining the response to CoVs infection. Rigorous design and robust statistical methods are warranted. [ABSTRACT FROM AUTHOR]