Changes in PD-1- and CTLA-4-bearing blood lymphocytes in ICU COVID-19 patients treated with Favipiravir/Kaletra or Dexamethasone/Remdesivir: a pilot study.

COVID-19, caused by SARS-CoV-2, requires new approaches to control the disease. Programmed cell death protein (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) play important roles in T-cell exhaustion in severe COVID-19. This study evaluated the frequency of whole blood lymphocytes expressing PD-1 and CTLA-4 in COVID-19 patients upon admission to the intensive care unit (ICU) (i.e., severe) or infection ward (i.e., moderate) and after 7 days of antiviral therapy. COVID-19 patients were treated with either favipiravir or Kaletra (FK group, 11 severe and 11 moderate) or dexamethasone plus remdesivir (DR group, 7 severe and 10 moderate) for 7 days in a pilot study. Eight healthy control subjects were also enrolled. The frequency of PD-1+ and CTLA-4+ lymphocytes in whole blood was evaluated by flow cytometry. Patients on DR therapy had shorter hospital stays than those on FK therapy. The frequency of PD-1+ lymphocytes in the FK group at baseline differed between COVID-19 patients and healthy controls, while the frequency of both PD-1+ and CTLA-4+ cells increased significantly 7 days of FK therapy. The response was similar in both moderate and severe patients. In contrast, the frequency of PD-1+ and CTLA-4+ lymphocytes varied significantly between patients and healthy controls before DR treatment. DR therapy enhanced PD-1+ but not the CTLA-4+ frequency of these cells after 7 days. We show that the frequency of PD-1 and CTAL-4-bearing lymphocytes during hospitalization was increased in Iranian ICU COVID-19 patients who received FK treatment, but that the frequency of CTLA-4+ cells was higher at baseline and did not increase in patients who received DR. The effectiveness of DR treatment may reflect differences in T-cell activation or exhaustion status, particularly in CTLA-4-expressing cells.

Effectiveness of different vaccine platforms in reducing mortality and length of ICU stay in severe and critical cases of COVID-19 in the Omicron variant era: A national cohort study in Iran.

Various severe acute respiratory syndrome coronavirus 2 vaccines with different platforms have been administered worldwide; however, their effectiveness in critical cases of COVID-19 has remained a concern. In this national cohort study, 24 016 intensive care unit (ICU) coronavirus disease-2019 (COVID-19) admissions were included from January to April 2022. The mortality and length of ICU stay were compared between the vaccinated and unvaccinated patients. A total of 9428 (39.25%) patients were unvaccinated, and 14 588 (60.75%) patients had received at least one dose of the vaccine. Compared with the unvaccinated, the first, second, and third doses of vaccine resulted in 8%, 20%, and 33% lower risk of ICU mortality in the adjusted model, with risk ratio (RR): 0.92, 95% confidence interval (CI): 0.84-1.001, RR: 0.80, 95% CI: 0.77-0.83, and RR: 0.67, 95% CI: 0.64-0.71, respectively. The mean survival time was significantly shorter in the unvaccinated versus the fully vaccinated patients (hazard ratio [HR]: 0.84, 95% CI: 0.80-0.88); p < 0.001). All vaccine platforms successfully decreased the hazard of ICU death compared with the unvaccinated group. The duration of ICU stay was significantly shorter in the fully vaccinated than in unvaccinated group (MD, -0.62, 95% CI: -0.82 to -0.42; p < 0.001). Since COVID-19 vaccination in all doses and platforms has been able to reduce the risk of mortality and length of ICU-stay, universal vaccination is recommended based on vaccine availability.

Nintedanib: a review of the properties, function, and usefulness to minimize COVID-19-induced lung injury.

INTRODUCTION: In severe COVID-19 patients, acute respiratory distress syndrome (ARDS)-induced lung injury regularly causes a pulmonary fibrotic phase. There is no approved therapy for the COVID-19-induced pulmonary fibrosis. However, administration of an anti-fibrotic agent, in the early acute phase of the severe COVID-19 with ARDS, may improve the infection outcomes. AREAS COVERED: In this review, the main characteristics of nintedanib and its usefulness to treat COVID-19-induced fibrosis were studied. In July 2022, a literature search was performed from PubMed, Google Scholar, and the WHO databases for studies focusing on the properties, function, efficacy, and safety of nintedanib against different lung injuries. EXPERT OPINION: Nintedanib interferes with lung fibrosis and tumor angiogenesis by targeting multiple receptor tyrosine kinases (RTKs). Loss of RTKs activity leads to blocking downstream signaling cascades and inhibiting the proliferation and migration of lung fibroblasts. Targeting RTKs may be useful in the treatment of COVID-19 lung fibrosis. Nintedanib may be a superior agent compared to pirfenidone for the treatment of COVID-19 ARDS-related pulmonary fibrosis. Investigation of the efficacy and safety of nintedanib in the early stages of COVID-19-induced ARDS is critical since it may decrease the oxygen dependency and degree of lung fibrosis after the hospital discharge.

Effectiveness of Borage plus syrup on COVID-19 patients in intensive care units.

Introduction: COVID-19 (coronavirus disease-2019) still causes a high rate of death globally with no definite curative treatment described. The traditional plant Borage (Borago officinalis L.) is a good source of gamma-linolenic (GLA). We hypothesized that Borage plus syrup (BPS) would be beneficial in severe COVID-19 patients within an intensive care unit (ICU) setting. Materials and methods: A pilot single center, randomized trial with no placebo was undertaken. A total of 60 PCR-positive severe COVID-19 participants admitted to ICU from June 2020-December 2020 at Masih Daneshvari Hospital Tehran-Iran gave informed consent. The participants were randomly assigned to either Borage Plus Syrup (BPS, 5 ml for 5 days) (n = 30) or standard care (IFN-ß and favipiravir) as a control group (n = 30). Pao2/Fio2, serum ferritin, CRP, bilirubin, IL-6, TNF-α, ALT, AST, PCT and serum IL-8 was measured upon admission and on release. Results: All the measured parameters decreased significantly with BPS treatment. In the control group, most parameters significantly improved apart from AST and PCT. In addition, the suppression of serum TNF levels in the BPS group was greater than that seen in the control group (P ≤ 0.05). Moreover, the length of ICU stay was significantly lower in the BPS group compared with the control group (P ≤ 0.05). Conclusion: Our study shows that addition of BPS to the standard treatment regime of COVID-19 patients in ICU improved outcomes and reduced the length of ICU treatment. Natural products could be considered as new approaches for reducting the harmful consequences of COVID-19.

Effectiveness of Borage plus syrup on COVID-19 patients in intensive care units

Introduction COVID-19 (coronavirus disease-2019) still causes a high rate of death globally with no definite curative treatment described. The traditional plant Borage (Borago officinalis L.) is a good source of gamma-linolenic (GLA). We hypothesized that Borage plus syrup (BPS) would be beneficial in severe COVID-19 patients within an intensive care unit (ICU) setting. Materials and methods A pilot single center, randomized trial with no placebo was undertaken. A total of 60 PCR-positive severe COVID-19 participants admitted to ICU from June 2020–December 2020 at Masih Daneshvari Hospital Tehran-Iran gave informed consent. The participants were randomly assigned to either Borage Plus Syrup (BPS, 5 ml for 5 days) (n = 30) or standard care (IFN-β and favipiravir) as a control group (n = 30). Pao2/Fio2, serum ferritin, CRP, bilirubin, IL-6, TNF-α, ALT, AST, PCT and serum IL-8 was measured upon admission and on release. Results All the measured parameters decreased significantly with BPS treatment. In the control group, most parameters significantly improved apart from AST and PCT. In addition, the suppression of serum TNF levels in the BPS group was greater than that seen in the control group (P ≤ 0.05). Moreover, the length of ICU stay was significantly lower in the BPS group compared with the control group (P ≤ 0.05). Conclusion Our study shows that addition of BPS to the standard treatment regime of COVID-19 patients in ICU improved outcomes and reduced the length of ICU treatment. Natural products could be considered as new approaches for reducting the harmful consequences of COVID-19.

Blood Purification Techniques, Inflammatory Mediators and Mortality in COVID-19 Patients.

BACKGROUND: Inflammatory mediators are an important component in the pathophysiology of the coronavirus disease 2019 (COVID-19). This study aimed to assess the effects of reducing inflammatory mediators using hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the mortality of patients with COVID-19. MATERIALS AND METHODS: Twelve patients with confirmed diagnosis of COVID-19 were included. All patients had acute respiratory distress syndrome (ARDS). Patients were divided into three groups, namely, HP, CRRT and HP+CRRT. The primary outcome was mortality and the secondary outcomes were oxygenation and reduction in inflammatory mediators at the end of the study. RESULTS: Patients were not different at baseline in demographics, inflammatory cytokine levels, and the level of acute phase reactants. Half of the patients (3 out of 6) in the HP+CRRT group survived along with the survival of one patient (1 out of 2) in the HP group. All four patients in the CRRT group died. Serum creatinine (SCr), Interleukin-1 (IL1), Interleukin-6 (IL6), Interleukin-8 (IL8), partial pressure of oxygen (PaO2), O2 saturation (O2 sat), and hemodynamic parameters improved over time in HP+CRRT and CRRT groups, but no significant difference was observed in the HP group (All Ps > 0.05). CONCLUSION: Combined HP and CRRT demonstrated the best result in terms of mortality, reduction of inflammatory mediators and oxygenation. Further investigations are needed to explore the role of HP+CRRT in COVID-19 patients.

Decreased neutrophil-mediated bacterial killing in COVID-19 patients.

The coronavirus disease COVID-19 was first described in December 2019. The peripheral blood of COVID-19 patients have increased numbers of neutrophils which are important in controlling the bacterial infections observed in COVID-19. We sought to evaluate the cytotoxic capacity of neutrophils in COVID-19 patients. 34 confirmed COVID-19 patients (29 severe, five mild disease), and nine healthy controls were recruited from the Masih Daneshvari Hospital (Tehran, Iran) from March to May 2020. Polymorphonuclear (PMN) cells were isolated from whole blood and incubated with green fluorescent protein (GFP)-labelled methicillin-resistant Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). Bacterial growth was determined by measuring the florescence of co-cultures of bacteria and neutrophils and reported as the lag time before exponential growth. The number of viable bacteria was determined after 70 hours as colony-forming units (CFU). The immunophenotype of tested cells was evaluated by flow cytometry. Isolated neutrophils have higher surface expression of CD16 and CD62L with negative markers for PMN-MDSC. Bacterial growth in the presence of SA (22 ± 0.9 versus 9.2 ± 0.5 h, P < .01) and PA (12.4 ± 0.6 versus 4.5 ± 0.22, P < .01) was significantly reduced in COVID-19 patients. After 70 h incubation of PMN with bacteria (SA and PA), CFUs were significant increased in COVID-19 patients SA (2.6 ± 0.09 × 108 CFU/mL-severe patients and 1.4 ± 0.06 × 108 CFU/mL-mild patients, P < .001) and PA (2.2 ± 0.09 × 109 CFU/mL-severe patients and 1.6 ± 0.03 × 109 CFU/mL-mild patients, P < .001). Gentamycin proliferation assays confirmed the presence of intracellular bacteria. Reduced bacterial killing by neutrophils from COVID-19 patients may be responsible for the high bacterial yield seen in these patients.

Increased Serum Levels of Soluble TNF-α Receptor Is Associated With ICU Mortality in COVID-19 Patients.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected over 112M patients and resulted in almost 2.5M deaths worldwide. The major clinical feature of severe COVID-19 patients requiring ventilation is acute respiratory distress syndrome (ARDS) possibly associated with a cytokine storm. Objectives: To elucidate serum levels of TNF-α and soluble TNF-Receptor 1 (sTNFR1) in patients with severe and mild COVID-19 disease as determinants of disease severity. Methods: We determined serum TNF-α and sTNFR1 concentrations in 46 patients with laboratory-confirmed COVID-19 (17 patients with severe disease within the intensive care unit [ICU] and 29 non-severe, non-ICU patients) and 15 healthy controls upon admission using ELISA. Subjects were recruited between March-May 2020 at the Masih Daneshvari Hospital Tehran, Iran. Results: Serum levels of sTNFRI were significantly higher in ICU patients (P<0.0001) and non-ICU patients (P=0.0342) compared with healthy subjects. Serum sTNFR1 were significantly higher in ICU patients than in non-ICU patients (P<0.0001). Serum TNF-α levels were greater in ICU and non-ICU patients than in the healthy subjects group (p<0.0001). The sTNFRI concentration in ICU (r=0.79, p=0.0002) and non-ICU (r=0.42, p=0.02) patients positively correlated with age although serum sTNFRI levels in ICU patients were significantly higher than in older healthy subjects. The sTNFRI concentration in ICU patients negatively correlated with ESR. Conclusions: The study demonstrates higher sTNFRI in ICU patients with severe COVID-19 disease and this be a biomarker of disease severity and mortality. Future studies should examine whether lower levels of systemic sTNFR1 at admission may indicate a better disease outcome.

Plasma exchange followed by convalescent plasma transfusion in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerged pandemic disease with no specific treatment. One of the potential treatments in newly found infectious disease is plasma exchange (PE) with convalescent plasma transfusion (CPT). This case series aimed to evaluate the primary PE and CPT in five Iranian COVID-19 patients. METHODS: Five patients with confirmed COVID-19 who had acute respiratory distress syndrome and were supported by mechanical ventilation were treated with two consecutive PE containing fresh frozen plasma (FFP) of healthy donors and 0.9 % saline solution containing 5 % human albumin. Thereafter, CPT was performed just like PE, except that the FFP in this step was substituted with convalescent ABO-matched plasma. Clinical and laboratory factors were evaluated before and after treatments. RESULTS: Three to Four patients showed lower body temperature and improved oxygen saturation as well as reduced laboratory factors such as c-reactive protein, lactate dehydrogenase, creatine phosphokinase (total and myocardial isoform), aspartate aminotransferase, blood urea nitrogen, bilirubin (total and direct), D-dimer, interleukin-6, and CD4+/CD8 + T cells ratio initially after PE and continued to improve so that they were discharged. One patient due to secondary hemophagocytic lymphohistiocytosis and extensive lung fungal infection was expired. DISCUSSION: Overall, the PE followed by CPT was beneficial in reducing acute inflammation led to a considerable improvement in patients' clinical features. It seems that PE along with CPT could provide clearance of pro-inflammatory mediators as well as the positive effects of CPT. Controlled studies are required to confirm the effect of PE/CPT compared with other therapeutic approaches.

No clinical benefit of high dose corticosteroid administration in patients with COVID-19: A preliminary report of a randomized clinical trial.

The aim of this study was to evaluate the clinical effects of dexamethasone administration in patients with mild to moderate acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). The study included 50 patients who were randomly assigned to the dexamethasone group or control group. Dexamethasone was administered at a dose of 20 mg/day from day 1-5 and then at 10 mg/day from day 6-10. The need for invasive mechanical ventilation, death rate, duration of clinical improvement, length of hospital stay, and radiological changes in the computed tomography scan were assessed. The results revealed that 92% and 96% of patients in the dexamethasone and control groups, respectively, required noninvasive ventilation (P = 0.500). Among them, 52% and 44% of patients in the dexamethasone and control groups, respectively, required invasive mechanical ventilation (P = 0.389). At the end of the study, 64% of patients in the dexamethasone group and 60% of patients in the control group died (P = 0.500); the remaining patients were discharged from the hospital during the 28-day follow-up period. The median length of hospital stay was 11 days in the dexamethasone group and 6 days in the control group (P = 0.036) and the median length of hospital stay was 7 days in the dexamethasone group and 3 days in the control group (P < 0.001). No significant differences were observed in the other outcomes. This study showed that corticosteroid administration had no clinical benefit in patients with COVID-19-induced mild to moderate ARDS.

A review on favipiravir: the properties, function, and usefulness to treat COVID-19.

INTRODUCTION: At this time, there is no specific therapeutic or vaccine for treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, available drugs for treatment of other viral infections may be useful to treat COVID-19. AREAS COVERED: The focus of the current review was studying the main characteristics of favipiravir and its usefulness to treat COVID-19. An electronic search was done by using Pubmed and Google scholar. EXPERT OPINION: Based on the mechanism of action and safety of favipiravir, the drug may be a promising candidate for compassionate use against the SARS-CoV-2 infection. Favipiravir has a wide range of activity against many single-stranded RNA viruses, is well tolerated in humans and has a high barrier to resistance. However, high doses of the agent are necessary to obtain an efficient antiviral activity. Favipiravir is teratogen in pregnant women and associated with the hyperuricemia. Therefore, the administration of the drug should be well controlled. Investigating the antiviral prophylactic potency of favipiravir and search for its pro-drugs and/or analogs showing improved activity and/or safety are critical.

Clinical Manifestations of Patients with Coronavirus Disease 2019 (COVID-19) in a Referral Center in Iran.

BACKGROUND: Following the recent epidemic of coronavirus disease 2019 (COVID-19) in Wuhan, China, a novel betacoronavirus was isolated from two patients in Iran on February 19, 2020. In this study, we aimed to determine the clinical manifestations and outcomes of the first confirmed cases of COVID-19 infection (n=127). MATERIALS AND METHODS: This prospective study was conducted on all COVID-19-suspected cases, admitted to Masih Daneshvari Hospital (a designated hospital for COVID-19), Tehran, Iran, since February 19, 2020. All patients were tested for COVID-19, using reverse transcription-polymerase chain reaction (RT-PCR) assay. Data of confirmed cases, including demographic characteristics, clinical features, and outcomes, were collected and compared between three groups of patients, requiring different types of admission (requiring ICU admission, admission to the general ward, and transfer to ICU). RESULTS: Of 412 suspected cases, with the mean age of 54.1 years (SD=13.4), 127 (31%) were positive for COVID-19. Following the patients' first visit to the clinic, 115 cases were admitted to the general ward, while ten patients required ICU admission. Due to clinical deterioration in the condition of 25 patients (out of 115 patients), ICU admission was essential. Based on the results, the baseline characteristics of the groups were similar. Patients requiring ICU admission were more likely to have multiorgan involvement (liver involvement, P<0.001; renal involvement, P<0.001; and cardiac involvement, P=0.02), low O2 saturation (P<0.001), and lymphopenia (P=0.05). During hospital admission, 21 (16.5%) patients died, while the rest (83.5%) were discharged and followed-up until March 26, 2020. Also, the survival rate of patients, who received immunoglobulin, was higher than other patients (60.87% vs. 39.13%). CONCLUSION: The mortality rate of COVID-19 patients was considerable in our study. Based on the present results, this infection can cause multiorgan damage. Therefore, intensive monitoring of these patients needs to be considered.

Plasmapheresis reduces cytokine and immune cell levels in COVID-19 patients with acute respiratory distress syndrome (ARDS).

BACKGROUND: In December 2019, pneumonia associated with a novel coronavirus (COVID-19) was reported in Wuhan, China. Acute respiratory distress syndrome (ARDS) is the most frequently observed complication in COVID-19 patients with high mortality rates. OBJECTIVE OF STUDY: To observe the clinical effect of plasmapheresis on excessive inflammatory reaction and immune features in patients with severe COVID-19 at risk of ARDS. MATERIALS AND METHODS: In this single-center study, we included 15 confirmed cases of COVID-19 at Masih Daneshvari Hospital, in March 2020 in Tehran, Iran. COVID-19 cases were confirmed by RT-PCR and CT imaging according to WHO guidelines. Plasmapheresis was performed to alleviate cytokine-induced ARDS. The improvement in oxygen delivery (PaO2/FiO2), total number of T cells, liver enzymes, acute reaction proteins, TNF-α and IL-6 levels were evaluated. RESULTS: Inflammatory cytokine levels (TNF-α, IL-6), and acute phase reaction proteins including ferritin and CRP were high before plasmapheresis. After plasmapheresis, the levels of PaO2/FiO2, acute phase reactants, inflammatory mediators, liver enzymes and bilirubin were significantly reduced within a week (p < 0.05). In contrast, although the number of T helper cells decreased immediately after plasmapheresis, they rose to above baseline levels after 1 week. Nine out of fifteen patients on non-invasive positive-pressure ventilation (NIPPV) survived whilst the six patients undergoing invasive mechanical ventilation (IMV) died. CONCLUSION: Our data suggests that plasmapheresis improves systemic cytokine and immune responses in patients with severe COVID-19 who do not undergo IMV. Further controlled studies are required to explore the efficacy of plasmapheresis treatment in patients with COVID-19.

A Fourteen-day Experience with Coronavirus Disease 2019 (COVID-19) Induced Acute Respiratory Distress Syndrome (ARDS): An Iranian Treatment Protocol.

COVID-19 is currently causing concern in the medical community as the virus is spreading around the world. It has a heavy global burden, particularly in low-income countries. The clinical spectrum of COVID-19 pneumonia ranges from mild to critically ill cases and Acute Respiratory Distress Syndrome. An expert panel was held and an internal protocol was developed to manage the COVID-19 induced ARDS according to WHO recommendations and NIH guidelines. Different therapeutic regimens were employed on this protocol based on the ARDS severity and the patients' special characteristics. The mortality rate, the rate of survivors, and non-survivors were reported. Of the 231 suspected cases of COVID-19 admitted to the hospital during two weeks, 72 patients were admitted to ICU with diagnosis confirmed by RT-PCR. In total, mortality in the ICU was 25% (n = 18) among ARDS patients over two weeks. COVID-19 induced ARDS is a major concern. The rapid progression of ARDS needs specific protocol based on patients' characteristics and rapid action.

Iran's Approach to COVID-19: Evolving Treatment Protocols and Ongoing Clinical Trials.

The coronavirus disease 2019 (COVID-19) pandemic is challenging the health care systems around the world and compelling them to timely share their strategies, tactics and experiences. Since mid-January, a huge volume of instructions has been released by Iran's Ministry of Health and Medical Education (MOHME) covering diverse aspects of disease control and prevention. In this study, we aimed to review the instructions published either before or after COVID-19's transmission to Iran to depict the clinical approach and therapeutics used in Iran to battle the current pandemic. We retrospectively gathered and critically reviewed all official situation reports, guidelines, guidance, flowcharts, protocols, recommendations and advice released by Iranian scientific, or administrative arms of action against COVID-19. The ongoing clinical trials approved by MOHME and registered to the Iranian Registry of Clinical Trials (IRCT) have been reviewed as well. Our study resulted in the following mainstays of Iran's approach to COVID-19: (i) active clinical screening; preferably on-line or on-phone, (ii) management of limited paraclinical resources; by using them as diagnostic tools rather than epidemiological, (iii) a trend toward outpatient care of mild-to-moderate cases; either confirmed or suspicious, with active scheduled follow-up, and (iv) avoidance of pharmacotherapy, as far as possible. The therapeutic and administrative instructions are still being actively updated with some recommendations different from the previous ones. Nevertheless, a common approach in the background could be detected, It seems that the instructions are conceptually in line with the first "National Guideline for 2019-nCoV" published on 20 January 2020. The screening has mainly been clinically oriented rather than being based on laboratory tests and MOHME seems to be following the approach of "early detection of symptomatic cases followed by early source control."

COVID-19 in Iran: A model for Crisis Management and Current Experience.

In February 2020, the first sample test was confirmed as positive for corona virus in Masih Daneshvari Hospital that is the reference center in Iran for all pulmonary and respiratory diseases. The decisions made in a hospital or organization to manage a crisis is very vital. Success in managing any crisis requires a scientific and scholarly attitude. This paper was distilled from experiences gained in Masih Daneshvari Hospital in Tehran, capital of Iran, in March 2020 at the stubborn time of coping and managing corona virus crisis. This study was conducted using participatory action research, a methodology which identifies problems in practice, and finds methods to solve them. This Action research involves five stages: statement of the problem, planning, data interpretation and analysis, action, and evaluation of the research process during performing the study. The whole hospital was equipped for corona virus patients in 10 phases during one week and 250 active beds were equipped for these patients. Three models, namely, "corona virus crisis management model", "Pharmaceutical care management in coronavirus crisis model" and "nursing in coronavirus crisis model" were planned and implemented. During one month of implementing these three models, the supervision team monitored the accurate implementation of instructions and resolving or revising the possible deficiencies and faults. The Masih Daneshvari crisis management model in coronavirus, can be a useful and applicable model in other corona virus centers.

A Review on Remdesivir: A Possible Promising Agent for the Treatment of COVID-19.

The novel coronavirus 2019 (2019-nCoV), formally named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel human infectious coronavirus. The disease caused by SARS-CoV-2 is named COVID-19. Development and manufacturing of specific therapeutics and vaccines to treat COVID-19 are time-consuming processes. At this time, using available conventional therapeutics along with other treatment options may be useful to fight COVID-19. In different clinical trials, efficacy of remdesivir (GS-5734) against Ebola virus has been demonstrated. Moreover, remdesivir may be an effective therapy in vitro and in animal models infected by SARS and MERS coronaviruses. Hence, the drug may be theoretically effective against SARS-CoV-2. Remdesivir is a phosphoramidate prodrug of an adenosine C-nucleoside. By entrance into respiratory epithelial cells in human, the prodrug is metabolized to a nucleoside triphosphate as the active form. The nucleoside analog inhibits the viral RNA-dependent RNA polymerase (RdRp) by competing with the usual counterpart adenosine triphosphate (ATP). The nucleoside analog is incorporated into the generating RNA strand and causes a delayed stop in the viral replication process. Knowledge about the potential efficacy of remdesivir against coronaviruses has been restricted to in vitro studies and animal models. However, information related to COVID-19 is rapidly growing. Several clinical trials are ongoing for the management of COVID-19 using remdesivir. In this study, characteristics of remdesivir and its usage for treatment of COVID-19 are reviewed based on an electronic search using PubMed and Google Scholar.