Corrigendum to ?Repurposing FDA-approved drugs to fight COVID-19 using in silico methods: Targeting SARS-CoV-2 RdRp enzyme and host cell receptors (ACE2, CD147) through virtual screening and molecular dynamic simulationsË® [Inform. Med. Unlocked 23 (2021) 1-9/100541].

[This corrects the article DOI: 10.1016/j.imu.2021.100541.].

Corrigendum to ?Repurposing FDA-approved drugs to fight COVID-19 using in silico methods: Targeting SARS-CoV-2 RdRp enzyme and host cell receptors (ACE2, CD147) through virtual screening and molecular dynamic simulationsË® [Inform. Med. Unlocked 23 (2021) 1-9/100541].

[This corrects the article DOI: 10.1016/j.imu.2021.100541.].

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.

An overview on the treatments and prevention against COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to plague the world. While COVID-19 is asymptomatic in most individuals, it can cause symptoms like pneumonia, ARDS (acute respiratory distress syndrome), and death in others. Although humans are currently being vaccinated with several COVID-19 candidate vaccines in many countries, however, the world still is relying on hygiene measures, social distancing, and approved drugs. RESULT: There are many potential therapeutic agents to pharmacologically fight COVID-19: antiviral molecules, recombinant soluble angiotensin-converting enzyme 2 (ACE2), monoclonal antibodies, vaccines, corticosteroids, interferon therapies, and herbal agents. By an understanding of the SARS-CoV-2 structure and its infection mechanisms, several vaccine candidates are under development and some are currently in various phases of clinical trials. CONCLUSION: This review describes potential therapeutic agents, including antiviral agents, biologic agents, anti-inflammatory agents, and herbal agents in the treatment of COVID-19 patients. In addition to reviewing the vaccine candidates that entered phases 4, 3, and 2/3 clinical trials, this review also discusses the various platforms that are used to develop the vaccine COVID-19.

Evaluation the efficacy and safety of N-acetylcysteine inhalation spray in controlling the symptoms of patients with COVID-19: An open-label randomized controlled clinical trial.

The aim of this study was to evaluate the effect and safety of N-acetylcysteine (NAC) inhalation spray in the treatment of patients with coronavirus disease 2019 (COVID-19). This randomized controlled clinical trial study was conducted on patients with COVID-19. Eligible patients (n = 250) were randomly allocated into the intervention group (routine treatment + NAC inhaler spray one puff per 12 h, for 7 days) or the control group who received routine treatment alone. Clinical features, hemodynamic, hematological, biochemical parameters and patient outcomes were assessed and compared before and after treatment. The mortality rate was significantly higher in the control group than in the intervention group (39.2% vs. 3.2%, p < 0.001). Significant differences were found between the two groups (intervention and control, respectively) for white blood cell count (6.2 vs. 7.8, p < 0.001), hemoglobin (12.3 vs. 13.3, p = 0.002), C-reactive protein (CRP: 6 vs. 11.5, p < 0.0001) and aspartate aminotransferase (AST: 32 vs. 25.5, p < 0.0001). No differences were seen for hospital length of stay (11.98 ± 3.61 vs. 11.81 ± 3.52, p = 0.814) or the requirement for intensive care unit (ICU) admission (7.2% vs. 11.2%, p = 0.274). NAC was beneficial in reducing the mortality rate in patients with COVID-19 and inflammatory parameters, and a reduction in the development of severe respiratory failure; however, it did not affect the length of hospital stay or the need for ICU admission. Data on the effectiveness of NAC for Severe Acute Respiratory Syndrome Coronavirus-2 is limited and further research is required.

Fully understanding the efficacy profile of the COVID-19 vaccination and its associated factors in multiple real-world settings.

We performed a review study according to recent COVID-19 vaccines' real-world data to provide comparisons between COVID-19 vaccines regarding their relative efficacy. Although most vaccine platforms showed comparable effectiveness and efficacy, we highlight critical points and recent developments generated in studies that might affect vaccine efficacy including population-dependent effects of the vaccine (transplantation, adiposity, and specific comorbidities, as well as older age, male sex, ethnicity, and prior infection), vaccine type, variants of concern (VOC), and an extended vaccine schedule. Owing to these factors, community-based trials can be of great importance in determining vaccine effectiveness in a systematic manner; thus, uncertainty remains regarding vaccine efficacy. Long immune protection of vaccination with BNT162b2 or ChAdOx1 nCoV-19 has been demonstrated to be up to 61 months and 5-12 months after the previous infection, and boosting infection-acquired immunity for both the first and second doses of the BNT162b2 and ChAdOx1 nCoV-19 vaccines was correlated with high and durable protection. However, large cohort and longitudinal studies are required for the evaluation of immunity dynamics and longevity in unvaccinated, vaccinated, and infected individuals, as well as vaccinated convalescent individuals in real-world settings. Regarding the likelihood of vaccine escape variants evolving, an ongoing examination of the protection conferred against an evolving virus (new variant) by an extended schedule can be crucial.

On Therapeutic Plasma Exchange Against Severe COVID-19-Associated Pneumonia: An Observational Clinical Study

Background There is a risk of novel mutations of SARS-CoV-2 that may render COVID-19 resistant to most of the therapies, including antiviral drugs and vaccines. The evidence around the application of therapeutic plasma exchange (TPE) for the management of critically ill patients with COVID-19 is still provisional, and further investigations are needed to confirm its eventual beneficial effects. Aims To assess the effect of TPE on the risk of mortality in patients with COVID-19-associated pneumonia, using three statistical procedures to rule out any threats to validity. Methods We therefore carried out a single-centered retrospective observational non-placebo-controlled trial enrolling 73 inpatients from Baqiyatallah Hospital in Tehran (Iran) with the diagnosis of COVID-19-associated pneumonia confirmed by real-time polymerase chain reaction (RT-qPCR) on nasopharyngeal swabs and high-resolution computerized tomography chest scan. These patients were broken down into two groups: Group 1 (30 patients) receiving standard care (corticosteroids, ceftriaxone, azithromycin, pantoprazole, hydroxychloroquine, lopinavir/ritonavir), and Group 2 (43 patients) receiving the above regimen plus TPE (replacing 2 l of patients' plasma by a solution, 50% of normal plasma, and 50% of albumin at 5%) administered according to various time schedules. The follow-up time was 30 days and all-cause mortality was the endpoint. Results Deaths were 6 (14%) in Group 2 and 14 (47%) in Group 1. However, different harmful risk factors prevailed among patients not receiving TPE rather than being equally split between the intervention and control group. We used an algorithm of structural equation modeling (of STATA) to summarize a large pool of potential confounders into a single score (called with the descriptive name “severity”). Disease severity was lower (Wilkinson rank-sum test p < 0.001) among patients with COVID-19 undergoing TPE (median: −2.82;range: −5.18;7.96) as compared to those not receiving TPE (median: −1.35;range: −3.89;8.84), confirming that treatment assignment involved a selection bias of patients according to the severity of COVID-19 at hospital admission. The adjustment for confounding was carried out using severity as the covariate in Cox regression models. The univariate hazard ratio (HR) of 0.68 (95%CI: 0.26;1.80;p = 0.441) for TPE turned to 1.19 (95%CI: 0.43;3.29;p = 0.741) after adjusting for severity. Conclusions In this study sample, the lower mortality observed among patients receiving TPE was due to a lower severity of COVID-19 rather than the TPE effects.

The impact of protein corona on the biological behavior of targeting nanomedicines.

For successful translation of targeting nanomedicines from bench to bedside, it is vital to address their most common drawbacks namely rapid clearance and off-target accumulation. These complications evidently originate from a phenomenon called "protein corona (PC) formation" around the surface of targeting nanoparticles (NPs) which happens once they encounter the bloodstream and interact with plasma proteins with high collision frequency. This phenomenon endows the targeting nanomedicines with a different biological behavior followed by an unexpected fate, which is usually very different from what we commonly observe in vitro. In addition to the inherent physiochemical properties of NPs, the targeting ligands could also remarkably dictate the amount and type of adsorbed PC. As very limited studies have focused their attention on this particular factor, the present review is tasked to discuss the best simulated environment and latest characterization techniques applied to PC analysis. The effect of PC on the biological behavior of targeting NPs engineered with different targeting moieties is further discussed. Ultimately, the recent progresses in manipulation of nano-bio interfaces to achieve the most favorite therapeutic outcome are highlighted.

Resveratrol as a Probable Multiheaded Treatment Approach for COVID-19.

The COVID-19 pandemic has plagued the world for more than 1 year now and has resulted in over 77 million cases and 1.7 million related deaths. While we await the rollout of the vaccines, new treatments are urgently needed to reduce the effects of this devastating virus. Here, we describe a number of preclinical studies which show promising effects of the polyphenol resveratrol.

The Primary Outcomes and Epidemiological and Clinical Features of Coronavirus Disease 2019 (COVID-19) in Iran.

AIM: We aimed to describe the epidemiological and clinical characteristics of Iranian patients with COVID-19. METHODS: In this single-center and retrospective study, patients with confirmed COVID-19 infections were enrolled. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with outcomes. RESULTS: Of 179 patients with confirmed COVID-19 infection, 12 remained hospitalized at the end of the study and 167 were included in the final analysis. Of these, 153 (91.6%) were discharged and 14 (8.38%) died in hospital. Approximately half (50.9%) of patients suffered from a comorbidity, with diabetes or coronary heart disease being the most common in 20 patients. The most common symptoms on admission were fever, dyspnea, and cough. The mean durations from first symptoms to hospital admission was 8.64 ± 4.14 days, whereas the mean hospitalization time to discharge or death was 5.19 ± 2.42 and 4.35 ± 2.70 days, respectively. There was a significantly higher age in non-survivor patients compared with survivor patients. Multivariate regression showed increasing odds ratio (OR) of in-hospital death associated with respiratory rates >20 breaths/min (OR: 5.14, 95% CI: 1.19-22.15, p = 0.028) and blood urea nitrogen (BUN) >19 mg/dL (OR: 4.54, 95% CI: 1.30-15.85, p = 0.017) on admission. In addition, higher respiratory rate was associated with continuous fever (OR: 4.08, 95% CI: 1.18-14.08, p = 0.026) and other clinical symptoms (OR: 3.52, 95% CI: 1.05-11.87, p = 0.04). CONCLUSION: The potential risk factors including high respiratory rate and BUN levels could help to identify COVID-19 patients with poor prognosis at an early stage in the Iranian population.

Repurposing FDA-approved drugs to fight COVID-19 using in silico methods: Targeting SARS-CoV-2 RdRp enzyme and host cell receptors (ACE2, CD147) through virtual screening and molecular dynamic simulations.

BACKGROUND: Different approaches have been proved effective for combating the COVID-19 pandemic. Accordingly, in silico drug repurposing strategy, has been highly regarded as an accurate computational tool to achieve fast and reliable results. Considering SARS-CoV-2's structural proteins and their interaction the host's cell-specific receptors, this study investigated a drug repurposing strategy aiming to screen compatible inhibitors of FDA-approved drugs against viral entry receptors (ACE2 and CD147) and integral enzyme of the viral polymerase (RdRp). METHODS: The study screened the FDA-approved drugs against ACE2, CD147, and RDRP by virtual screening and molecular dynamics (MD) simulation. RESULTS: The results of this study indicated that five drugs with ACE2, four drugs with RDRP, and seven drugs with CD147 achieved the most favorable free binding energy (ΔG < -10). This study selected these drugs for MD simulation investigation whose results demonstrated that ledipasvir with ACE2, estradiol benzoate with CD147, and vancomycin with RDRP represented the most favorable ΔG. Also, paritaprevir and vancomycin have good binding energy with both targets (ACE2 and RdRp). CONCLUSIONS: Ledipasvir, estradiol benzoate, and vancomycin and paritaprevir are potentially suitable candidates for further investigation as possible treatments of COVID-19 and novel drug development.

The clinical value of two combination regimens in the Management of Patients Suffering from Covid-19 pneumonia: a single centered, retrospective, observational study.

BACKGROUND: There is no identified pharmacological therapy for COVID-19 patients, where potential therapeutic strategies are underway to determine effective therapy under such unprecedented pandemic. Therefore, combination therapies may have the potential of alleviating the patient's outcome. This study aimed at comparing the efficacy of two different combination regimens in improving outcomes of patients infected by novel coronavirus (COVID-19). METHODS: This is a single centered, retrospective, observational study of 60 laboratory-confirmed COVID-19 positive inpatients (≥18 years old) at two wards of the Baqiyatallah Hospital, Tehran, Iran. Patient's data including clinical and laboratory parameters were recorded. According to the drug regimen, the patients were divided into two groups; group I who received regimen I consisting azithromycin, prednisolone, naproxen, and lopinavir/ritonavir and group II who received regimen II including meropenem, levofloxacin, vancomycin, hydroxychloroquine, and oseltamivir. RESULTS: The oxygen saturation (SpO2) and temperature were positively changed in patients receiving regimen I compared to regimen II (P = 0.013 and P = 0.012, respectively). The serum level of C-reactive protein (CRP) changed positively in group I (P < 0.001). Although there was a significant difference in platelets between both groups (75.44 vs 51.62, P < 0.001), their change did not clinically differ between two groups. The findings indicated a significant difference of the average length of stay in hospitals (ALOS) between two groups, where the patients under regimen I showed a shorter ALOS (6.97 vs 9.93, P = 0.001). CONCLUSION: This study revealed the beneficial effect of the short-term use of low-dose prednisolone in combination with azithromycin, naproxen and lopinavir/ritonavir (regimen I), in decreasing ALOS compared to regimen II. Since there is still lack of evidence for safety of this regimen, further investigation in our ongoing follow-up to deal with COVID-19 pneumonia is underway. Graphical abstract.

The role of extracellular vesicles in COVID-19 virus infection.

Extracellular vesicles releasing from various types of cells contribute to intercellular communication via delivering bio-molecules like nucleic acids, proteins, and lipids to recipient cells. Exosomes are 30-120 nm extracellular vesicles that participate in several pathological conditions. Virus-infected cells release exosomes that are implicated in infection through transferring viral components such as viral-derived miRNAs and proteins. As well, exosomes contain receptors for viruses that make recipient cells susceptible to virus entry. Since December 2019, SARS-CoV-2 (COVID-19) infection has become a worldwide urgent public health concern. There is currently no vaccine or specific antiviral treatment existing for COVID-19 virus infection. Hence, it is critical to find a safe and effective therapeutic tool to patients with severe COVID-19 virus infection. Extracellular vesicles may contribute to spread this virus as they transfer such receptors as CD9 and ACE2, which make recipient cells susceptible to virus docking. Upon entry, COVID-19 virus may be directed into the exosomal pathway, and its component is packaged into exosomes for secretion. Exosome-based strategies for the treatment of COVID-19 virus infection may include following items: inhibition of exosome biogenesis and uptake, exosome-therapy, exosome-based drug delivery system, and exosome-based vaccine. Mesenchymal stem cells can suppress nonproductive inflammation and improve/repair lung cells including endothelial and alveolar cells, which damaged by COVID-19 virus infection. Understanding molecular mechanisms behind extracellular vesicles related COVID-19 virus infection may provide us with an avenue to identify its entry, replication, spreading, and infection to overcome its adverse effects.