Laboratory Parameters in Detection of COVID-19 Patients with Positive RT-PCR; a Diagnostic Accuracy Study.

INTRODUCTION: The role of laboratory parameters in screening of COVID-19 cases has not been definitely established. This study aimed to evaluate the accuracy of laboratory parameters in predicting cases with positive RT-PCR for COVID-19. METHODS: This diagnostic accuracy study was conducted on suspected COVID-19 patients, who presented to Behpooyan Clinic Medical center in Tehran (Iran) from 22 February to 14 March, 2020. Patients were divided into two groups based on the results of real time reverse transcriptase-polymerase chain reaction (RT-PCR) for COVID-19, and the accuracy of different laboratory parameters in predicting cases with positive RT-PCR was evaluated using area under the ROC curve (AUC). RESULTS: Two hundred cases with the mean age of 41.3± 14.6 (range: 19-78) years were studied (0.53% male). The result of RT-PCR for COVID-19 was positive in 70 (35%) cases. Patients with positive RT-PCR had significantly higher neutrophil (NEU) count (p = 0.0001), and C-reactive protein (CRP) (p = 0.04), lactate dehydrogenase (LDH) (p = 0.0001), aspartate aminotransferase (AST) (p = 0.001), alanine aminotransferase (ALT) (p = 0.0001), and Urea (p = 0.001) levels in serum. In addition, patients with positive RT-PCR had lower white blood cell (WBC) count (p = 0.0001) and serum albumin level (p = 0.0001) compared to others. ALT (AUC = 0.879), CRP (AUC = 0.870), NEU (AUC = 0.858), LDH (AUC = 0.835), and Urea (AUC = 0.835) had very good accuracy in predicting cases with positive RT-PCR for COVID-19, respectively. CONCLUSION: Our findings suggest that level of LDH, CRP, ALT and NEU can be used to predict the result of COVID-19 test. They can help in detection of COVID-19 patients.

Association between serum inflammatory parameters and the disease severity in COVID-19 patients.

OBJECTIVE: Most patients infected with the novel coronavirus (SARS-CoV-2), as the causative agent of COVID-19 disease, show mild symptoms, but some of them develop severe illness. The purpose of this study was to analyze the blood markers of COVID-19 patients and to investigate the correlation between serum inflammatory cytokines and the disease severity. METHODS: In this prospective cross-sectional study, 50 patients with COVID-19 and 20 patients without COVID-19 were enrolled. According to ICU admission criteria, patients were divided into two groups of non-severe and severe. Differences in the serum levels of C-reactive protein (CRP), IL-6, and TNF-α, as well as erythrocyte sedimentation rate (ESR), lymphocytes (LYM) count, and neutrophils (NEU) count between the two groups were determined and analyzed. RESULTS: Out of the 50 patients with COVID-19, 14 were diagnosed as severe cases. There was no significant difference between the two groups of COVID-19 patients in terms of gender and age. Blood tests of COVID-19 patients showed a significant decrease and increase in NEU and LYM counts, respectively. There were significant differences in the serum levels of IL-6, TNF-α, and CRP between the severe and non-severe groups, which were higher in the severe group. Also, there was a significant correlation between the disease severity and CRP with ESR (r = 0.79), CRP with IL-6 (r = 0.74), LYM with NEU (r = -0.97), and ESR with TNF-α (r = 0.7). CONCLUSION: The findings of this study, as the first study in Iran, suggest that the levels of IL-6, TNF-α, ESR, and CRP could be used to predict the severity of COVID-19 disease.

Neutrophil to lymphocyte ratio and C-reactive protein level as prognostic markers in mild versus severe COVID-19 patients.

AIM: This research aimed to investigate neutrophil-to-lymphocyte ratio (NLR) with C-reactive protein to identify potential clinical predictors and analyze differences among severe and non-severe COVID-19 patients. BACKGROUND: NLR and CRP are established markers that reflect systemic inflammatory, and these parameters alter in patients with novel coronavirus (SARS-CoV-2) pneumonia (COVID-19). METHODS: A population of patients with COVID-19 referred to Loghman Hospital in Tehran was analyzed. The baseline data of laboratory examinations, including NLR and CRP levels, was collected. Pearson analysis was used to assess the independent relationship between the NLR with disease severity and CRP levels. RESULTS: COVID-19 cases comprised 14 (20%) patients with severe disease and 56 (80%) with non-severe infection. The mean values of WBC, NEU, LYM, and NLR of the severe patients were significantly higher than those of the non-severe patients. Forty-six patients (65.7%) had NLR >1, and the remaining patients had NLR <1. Plasma CRP levels were higher in severe cases than in non-severe cases, and this difference was significant. The results showed that NLR was positively correlated with CRP levels (R=0.23) and negatively correlated with WBC (R=-0.38). CRP (AUC = 0.97, 95% CI: 0.95-0.99) and NLR (AUC = 0.87, 95% CI: 0.81-0.93) had very good accuracy in predicting the severity of COVID-19 disease. CONCLUSION: The findings of this study indicated that the integration of NLR and CRP may lead to improved predictions and is recommended as a valuable early marker to assess prognosis and evaluate the severity of clinical symptoms in COVID-19 patients.

Computation screening and molecular docking of FDA approved viral protease inhibitors as a potential drug against COVID-19.

AIM: This study demonstrated potent inhibitors against COVID-19 using the molecular docking approach of FDA approved viral antiprotease drugs. BACKGROUND: COVID-19 has now spread throughout world. There is a serious need to find potential therapeutic agents. The 3C-like protease (Mpro/6LU7) is an attractive molecular target for rational anti-CoV drugs. METHODS: The tertiary structure of COVID-19 Mpro was obtained from a protein data bank repository, and molecular docking screening was performed by Molegro Virtual Docker, ver. 6, with a grid resolution of 0.30 Å. Docking scores (DOS) are representative of calculated ligand-receptor (protein) interaction energy; therefore, more negative scores mean better binding tendency. Another docking study was then applied on each of the selected drugs with the best ligands separately and using a more accurate RMSD algorithm. RESULTS: The docking of COVID-19 major protease (6LU7) with 17 selected drugs resulted in four FDA approved viral antiprotease drugs (Temoporfin, Simeprevir, Cobicistat, Ritonavir) showing the best docking scores. Among these 4 compounds, Temoporfin exhibited the best DOS (-202.88) and the best screened ligand with COVID-19 Mpro, followed by Simeprevir (-201.66), Cobicistat (-187.75), and Ritonavir (-186.66). As the best screened ligand, Temoporfin could target the Mpro with 20 different conformations, while Simeprevir, Cobicistat, and Ritonavir make 14, 10, and 10 potential conformations at the binding site, respectively. CONCLUSION: The findings showed that the four selected FDA approved drugs can be potent inhibitors against COVID-19; among them, Temoporfin may be more potent for the treatment of the disease. Based on the findings, it is recommended that in-vitro and in-vivo evaluations be conducted to determine the effectiveness of these drugs against COVID-19.

Severe acute respiratory syndrome-coronavirus-2 spike (S) protein based vaccine candidates: State of the art and future prospects.

Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which is responsible for a global pandemic that started in late 2019 in Wuhan, China. To prevent the worldwide spread of this highly pathogenic virus, development of an effective and safe vaccine is urgently needed. The SARS-CoV-2 and SARS-CoV share a high degree of genetic and pathologic identity and share safety and immune-enhancement concerns regarding vaccine development. Prior animal studies with first generation (whole virus-based) preparations of SARS-CoV vaccines (inactivated and attenuated vaccine modalities) indicated the possibility of increased infectivity or eosinophilic infiltration by immunization. Therefore, development of second and third generation safer vaccines (by using modern vaccine platforms) is actively sought for this viral infection. The spike (S) protein of SARS-CoVs is the main determinant of cell entry and tropism and is responsible for facilitating zoonosis into humans and sustained person-to-person transmission. Furthermore, 'S' protein contains multiple neutralizing epitopes that play an essential role in the induction of neutralizing antibodies (nAbs) and protective immunity. Moreover, T-cell responses against the SARS-CoV-2 'S' protein have also been characterized that correlate to the IgG and IgA antibody titres in Covid-19 patients. Thus, S protein is an obvious candidate antigen for inclusion into vaccine platforms against SARS-CoV-2 viral infection. This manuscript reviews different characteristics of S protein, its potency and 'state of the art' of the vaccine development strategies and platforms using this antigen, for construction of a safe and effective SARS-CoV-2 vaccine.