Drug therapy in hospitalized patients with very severe symptoms following COVID-19

Implication for health policy/practice/research/medical education: To treat COVID-19, the first choice should be antiviral drugs and sometimes a small dose of anti-inflammatory drugs to reduce inflammation. In this regard, chloroquine has both features including antiviral activity and anti-inflammatory effect.Copyright © 2020 The Author(s);.

Covid 19 Pandemic: An Overview

In the 1930's the corona virus was first identified as a highly contagious chicken respiratory virus. Two human coronaviruses were later identified, the human coronavirus 229E causing the flu and secondly the human coronavirus OC43. Others are also important as SARS-CoV. In late 2019 the outbreak of Pneumonia occurred in the Chinese city of Wuhan which was investigated as a result of the corona virus, renamed as 2019-nCoV by the World Health Organization (WHO) and. now called as SARS-CoV-2. The WHO has identified the global health problem as an epidemic. Respiratory droplets produced during coughing and sneezing are the main means of transmission of COVID-19. Infection with COVID-19 in an infected person may remain undetected. Common symptoms of fever and dry cough are less common in the production of sputum, fatigue and in some cases may be dyspnoea or shortness of breath. The COVID-19 virus is a type of RNA virus, the outer envelope containing a lipid bilayer in which various proteins are synthesized such as membrane (M), envelope (E) and spike (S). Hand washing, coughing, social isolation, wearing a face mask in public, disinfection areas, and isolation are various ways to prevent the disease. The diagnosis of COVID-19 can be made on the basis of symptoms and confirmed using reverse transcription polymerase chain reaction (RT-PCR) tests. There are currently no antiretroviral drugs approved for COVID-19, only symptomatic and supportive treatment is used to treat people with this viral infection. Drugs that have been approved for the purpose of treating other viral infections are under investigation. Vaccination is an ultimate prevention and protection;few vaccines are given emergency approval and some are in progressive development phase in various countries to prevent this deadly pandemic.

A guide to COVID-19 antiviral therapeutics: a summary and perspective of the antiviral weapons against SARS-CoV-2 infection.

Antiviral therapies are integral in the fight against SARS-CoV-2 (i.e. severe acute respiratory syndrome coronavirus 2), the causative agent of COVID-19. Antiviral therapeutics can be divided into categories based on how they combat the virus, including viral entry into the host cell, viral replication, protein trafficking, post-translational processing, and immune response regulation. Drugs that target how the virus enters the cell include: Evusheld, REGEN-COV, bamlanivimab and etesevimab, bebtelovimab, sotrovimab, Arbidol, nitazoxanide, and chloroquine. Drugs that prevent the virus from replicating include: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, and Kaletra. Drugs that interfere with protein trafficking and post-translational processing include nitazoxanide and ivermectin. Lastly, drugs that target immune response regulation include interferons and the use of anti-inflammatory drugs such as dexamethasone. Antiviral therapies offer an alternative solution for those unable or unwilling to be vaccinated and are a vital weapon in the battle against the global pandemic. Learning more about these therapies helps raise awareness in the general population about the options available to them with respect to aiding in the reduction of the severity of COVID-19 infection. In this 'A Guide To' article, we provide an in-depth insight into the development of antiviral therapeutics against SARS-CoV-2 and their ability to help fight COVID-19.

Case Report of 78-Year-Old Man With Meningitis, Pulmonary Thromboembolism and SARS-Coronavirus-2 Infection

The novel coronavirus infection involves both the Central and Peripheral Nervous systems. Some of the presentations include acute cerebrovascular disease, impaired consciousness, transverse myelitis, encephalopathy, encephalitis, and epilepsy. Our patient was a 78-year-old man with dementia and diabetic nephropathy who was admitted two times for possibly COVID-19 infection. At the first hospitalization, the patient is treated with hydroxychloroquine and Kaletra based on clinical symptoms and initial laboratory findings due to suspicion of COVID-19. After the negative RT-PCR test of the nasopharyngeal sample for COVID-19 and evidence of aspiration pneumonia in CT scan, the patient was discharged with oral antibiotics. Five weeks later, he was rehospitalized with loss of consciousness, fever, and hypoxemia in the physical exam;he had neck stiffness in all directions, So the central nervous system (CNS) infection was suspected, the cerebrospinal fluid (CSF) sample was in favor of aseptic meningitis and second RT-PCR test of nasopharyngeal sample for COVID-19 was positive, but Brain MRI just showed small vessel disease without evidence of encephalitis. In the second hospitalization, he had acute renal failure, which was treated with supportive care, and also suffered from pulmonary embolism with cavitary lesions in his lungs. Meningitis with pulmonary embolism and acute renal failure have not yet been reported. Our patient is the first one, so we decided to share it. This case showed a different presentation of COVID-19 without typical lung involvement. So, we must pay attention to any signs and symptoms in a patient suspected of having a COVID-19.

Efficiency of antiviral treatment in COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is responsible for generating a global effort to discover urgent therapeutic solutions to limit the human damage caused by COVID-19. In the period of April to June 2020, 105 patients diagnosed with COVID-19 met the conditions for inclusion in the present study. They were treated with antiviral therapy according to local guidelines: D group (53 cases), treated with darunavir/ritonavir (DRV/r); and K group (52 cases), treated with lopinavir/ritonavir (LPV/r). Patients from the K group required 7.5 days of hospitalization less compared to those from the D group (P<0.001). The blood oxygen saturation values recorded in the groups were statistically different [K group (94.02±3.12%) vs. D group (92.13±4.24%), P=0.010]. The percentage of patients with unsatisfactory clinical evolution were non-significantly higher in the D group compared with the K group [20 (37.74%) vs. 12 (23.08%), P=0.157]. We did not note statistically significant differences between the two groups tracked considering the values for the Brescia-COVID Respiratory Severity Scale (BCRSS) of the patients with unsatisfactory clinical evolution, nor of the chest CT' evolution after 10 days of therapy. We did not register significant adverse effects after antiviral therapy in the two groups. Antiviral therapy with LPV/r had some favorable results compared to DRV/r in patients with COVID-19. Both therapies were well tolerated.

Drug-drug interactions with candidate medications used for COVID-19 treatment: An overview.

Drug-drug interaction (DDI) is a common clinical problem that has occurred as a result of the concomitant use of multiple drugs. DDI may occur in patients under treatment with medications used for coronavirus disease 2019 (COVID-19; i.e., chloroquine, lopinavir/ritonavir, ribavirin, tocilizumab, and remdesivir) and increase the risk of serious adverse reactions such as QT-prolongation, retinopathy, increased risk of infection, and hepatotoxicity. This review focuses on summarizing DDIs for candidate medications used for COVID-19 in order to minimize the adverse reactions.

Efficacy and Safety of Lopinavir/Ritonavir for Treatment of COVID-19: A Systematic Review and Meta-Analysis.

(Background) Lopinavir-ritonavir (LPV/RTV) is a human immunodeficiency virus (HIV) antiviral combination that has been considered for the treatment of COVID-19 disease. (Aim) This systematic review aimed to assess the efficacy and safety of LPV/RTV in COVID-19 patients in the published research. (Methods) A protocol was developed based on the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement. Articles were selected for review from 8 electronic databases. This review evaluated the effects of LPV/RTV alone or in combination with standard care ± interferons/antiviral treatments compared to other therapies, regarding duration of hospital stay, risk of progressing to invasive mechanical, time to virological cure and body temperature normalization, cough relief, radiological progression, mortality and safety. (Results) A consensus was reached to select 32 articles for full-text screening; only 14 articles comprising 9036 patients were included in this study; and eight of these were included for meta-analysis. Most of these studies did not report positive clinical outcomes with LPV/RTV treatment. In terms of virological cure, three studies reported less time in days to achieve a virological cure for LPV/RTV arm relative to no antiviral treatment (-0.81 day; 95% confidence interval (CI), -4.44 to 2.81; p = 0.007, I2 = 80%). However, the overall effect was not significant (p = 0.66). When comparing the LPV/RTV arm to umifenovir arm, a favorable affect was observed for umifenovir arm, but not statically significant (p = 0.09). In terms of time to body normalization and cough relief, no favorable effects of LPV/RTV versus umifenovir were observed. The largest trials (RECOVERY and SOLIDARITY) have shown that LPV/RTV failed to reduce mortality, initiation of invasive mechanical ventilation or hospitalization duration. Adverse events were reported most frequently for LPV/RTV (n = 84) relative to other antivirals and no antiviral treatments. (Conclusions) This review did not reveal any significant advantage in efficacy of LPV/RTV for the treatment of COVID-19 over standard care, no antivirals or other antiviral treatments. This result might not reflect the actual evidence.

Strategies for the development of drugs targeting novel coronavirus 2019-nCoV / 药学学报

@# There is no specific drug that has been approved for 2019-nCoV. There are a number of factors that pose major challenges in their development. Approaches to the development of anti-2019-nCoV include screening existing broad-spectrum antiviral drugs, repositioning of readily available clinical compounds, and <italic>de novo</italic> development of novel and specific agents for 2019-nCoV. Candidate compounds can be developed either to inhibit virus-based targets, such as RNA proteases, polymerase, spike glycoproteins, and viral envelop and membrane proteins, or to inhibit host-based targets, such as receptors and proteases that are utilized by virus for viral entry and endocytosis. Recently, the RNA polymerase remdesivir had demonstrated clinical efficacy in one patient with severe novel coronavirus pneumonia (NCP). The broad-spectrum viral protease inhibitor Kaletra^® is also recommended in the current NCP clinical practice. Both drugs had lately been proceeded into multiple controlled phase III clinical trials to test their safety and efficacy in NCP. Combinational therapies consisting of multiple drugs provide other viable options against 2019-nCoV, based on scientific and clinical rationales. Using bioinformatics and database analysis, we have identified 75 clinically compounds, including 20 marketed compounds, that are efficacious in inhibiting key targets in virus- and host-based approaches, which may facilitate the development of new therapeutic options for 2019-nCoV.