A comparative study of laboratory findings in PCR-positive and PCR-negative COVID-19 hospitalized patients.

INTRODUCTION: Given the many misconceptions in terms of both diagnosis and treatment, SARS-CoV-2 continues to infect and victimize. Notwithstanding molecular testing is the gold standard method of in vitro diagnostic, the often long-waiting time, as well as false-negative results are daunting challenges facing us. In this study, we aimed to report the diagnostic value of laboratory findings in COVID-19 patients, with an extensive focus on the differences between PCR-positive and PCR-negative cases. PATIENTS AND METHODS: We did a retrospective single-centre study on a large cohort of 1546 COVID-19 patients in Tehran, Iran. Based on clinical symptoms, chest CTs were performed for all the patients. Also, molecular testing of swab specimens was also performed for 1450 cases. RESULTS: All the data on laboratory results were retrospectively extracted from medical records. Of the 1546 patients, 1040 (67.5%) were male and 506 (32.5%) were female with the mean age of 55.67. On admission, 31.4% of the whole study population displayed lymphopenia and 38.9% showed neutrophilia. Decreased hemoglobin and mild thrombocytopenia were also found in 40% and 18.6% of cases, respectively. Elevated lactate dehydrogenase in nearly 75% of COVID-19 cases was the most common alteration amongst biochemical parameters which together with increased ESR and CRP could serve as diagnostic markers in SARS-CoV-2 infection. Of the 1450 patients with a PCR result, 439 (28.3%) were PCR-negative and 1011 (65.3%) were PCR-positive. Notably, lymphopenia and increased AST were higher in the PCR-positive group than their negative counterparts. Albeit being in the normal range, a significant decrease in the number of monocytes was also evident in the PCR-positive cases. CONCLUSIONS: As far we are aware, this is the first time that we reported a comprehensive exploration of laboratory characteristics of a large cohort of hospitalized COVID-19 patients from Iran, hoping that these data will cast more light on the diagnostic significance of these parameters.

Safety and immunogenicity of a recombinant receptor-binding domain-based protein subunit vaccine (Noora vaccine™) against COVID-19 in adults: A randomized, double-blind, placebo-controlled, Phase 1 trial.

The development of a safe and effective vaccine is essential to protect populations against coronavirus disease 2019 (COVID-19). There are several vaccine candidates under investigation with different mechanisms of action. In the present study, we have evaluated the safety and immunogenicity of a recombinant receptor-binding domain (RBD)-based protein subunit vaccine (Noora vaccine) against COVID-19 in adults. This Phase 1 trial is a randomized, double-blind, placebo-controlled study to evaluate the safety and immunogenicity of the recombinant RBD-based protein subunit vaccine (Noora vaccine) against COVID-19 in healthy adults volunteers. Eligible participants were included in this study after evaluating their health status and considering the exclusion criteria. They were then randomized into three groups and received three doses of vaccine (80 µg, 120 µg, and placebo) on Days 0, 21, and 35. Primary outcomes including solicited, unsolicited, and medically attended adverse events were recorded during this study. Secondary outcomes including the humoral and cellular immunity (including anti-RBD IgG antibody and neutralizing antibody) were measured on Days 0, 21, 28, 35, 42, and 49 by using the ELISA kit and the Virus Neutralization Test (VNT) was performed on day 49. Totally 70 cases were included in this Phase 1 trial and 60 of them completed the study. Safety assessments showed no severe adverse events. Local pain at the vaccine injection site occurred in 80% of the vaccinated volunteers. Induration and redness at the injection site were the other adverse reactions of this vaccine. There was no significant difference between the studied groups regarding adverse reactions. Anti-RBD IgG antibody and neutralizing antibody assessment showed significant seroconversion in comparison to the placebo group (80%, and 100% respectively, p < 0.001). The cellular immunity panel also showed mild to moderate induction of TH1 responses and the VNT showed 78% of seroprotection. The results of this Phase 1 trial showed acceptable safety without serious adverse events and significant seroconversions in the humoral and cellular immunity panel. The dose of 80 µg is an appropriate dose for injection in the next phases of the trial.

Efficient Framework for Detection of COVID-19 Omicron and Delta Variants Based on Two Intelligent Phases of CNN Models.

Introduction: While the COVID-19 pandemic was waning in most parts of the world, a new wave of COVID-19 Omicron and Delta variants in Central Asia and the Middle East caused a devastating crisis and collapse of health-care systems. As the diagnostic methods for this COVID-19 variant became more complex, health-care centers faced a dramatic increase in patients. Thus, the need for less expensive and faster diagnostic methods led researchers and specialists to work on improving diagnostic testing. Method: Inspired by the COVID-19 diagnosis methods, the latest and most efficient deep learning algorithms in the field of extracting X-ray and CT scan image features were used to identify COVID-19 in the early stages of the disease. Results: We presented a general framework consisting of two models which are developed by convolutional neural network (CNN) using the concept of transfer learning and parameter optimization. The proposed phase of the framework was evaluated on the test dataset and yielded remarkable results and achieved a detection sensitivity, specificity, and accuracy of 0.99, 0.986, and 0.988, for the first phase and 0.997, 0.9976, and 0.997 for the second phase, respectively. In all cases, the whole framework was able to successfully classify COVID-19 and non-COVID-19 cases from CT scans and X-ray images. Conclusion: Since the proposed framework was based on two deep learning models that used two radiology modalities, it was able to significantly assist radiologists in detecting COVID-19 in the early stages. The use of models with this feature can be considered as a powerful and reliable tool, compared to the previous models used in the past pandemics.

The Association of Age, Sex, and RT-PCR Results with the Lymphocyte and Neutrophil Counts in SARS-CoV-2 Infection: A Cross-sectional Analysis of 1450 Iranian Patients with COVID-19 The Association of Age, Sex, and RT-PCR Results with Neutrophil-to-lymphocyte Ratio in COVID-19

Containment of pandemic infections mainly depends on prompt identification of carriers, achievable through strict surveillance and truthful diagnostic testing. Although molecular identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the gold standard method, its low sensitivity and long turnaround time are among major concerns. In this retrospective single-center study, we reviewed the results of the lymphocyte and neutrophil counts of 1450 Iranian patients with coronavirus disease 2019 (COVID-19) recruited at Baqiyatallah Hospital, Tehran, Iran. Of 1450 patients, 439 cases (30.3%) were polymerase chain reaction (PCR) negative;further emphasizing that getting negative molecular testing is not as reliable as a positive result. While the lymphocyte count in cases with less than 50 years old was 1.8×103/µL (1.2-2.5), it was 1.47×103/µL (0.84-2.16) in the older group (p<0.001). Also, men experienced lower lymphocytes as compared to women (1.53×103/µL vs 1.76×103/µL;p=0.002). Of particular interest, the lymphocyte count in the PCR-negative cases was 1.77×103/µL (0.98-2.45) which was significantly higher than its count in their positive counterparts (1.53×103/µL;p=0.004). Unlike lymphocytes, sex and PCR did not significantly affect the number of neutrophils. The odds ratio for neutrophilia in patients aged older than 50, either with a negative or a positive PCR, was 2.46 and 2.23, suggesting old age as the most significant associated factor. The number of lymphocytes along with increased neutrophil count may probably serve as simple, rapid, and economical biomarkers, and are seemingly appropriate items that should be taken into account in the identification of patients with COVID-19, especially those aged more than 50.

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 risk factors and related hospitalizations for cases with positive and negative COVID-19 tests: A case-control study.

BACKGROUND: The aim of this study was to evaluate the risk factors for hospitalizations of cases with positive and negative COVID-19 tests. METHODS: In this case-control study, the case and control groups consisted of 292 COVID-19 patients and 296 non-COVID-19 patients. Patients who referred to a reference laboratory in Tehran (Iran) in March 2020 were selected and interviewed. The patients were contacted by telephone and data were recorded through a questionnaire. RESULTS: The sample of this study consisted of 588 patients (349 [59%] females, 239 [41%] males) with a mean age of 42 ± 15. The results of this study showed that comorbidities like diabetes (OR = 7.42), hypertension (OR = 4.85), asthma and respiratory diseases (OR = 5.64) in addition to symptoms including fever (OR = 6.67), chills (OR = 11.2), anorexia (OR = 11.3), dyspnea (OR = 4.8), weakness and lethargy (OR = 5.7) were the most predictive variables for hospitalization of non-COVID-19 cases. Furthermore, demographical variables like male gender (OR = 3.71), high age (>50; OR = 3.12), BMI (>25; OR = 2.37), travel (OR = 2.79), comorbidities including diabetes (OR = 5.26), hypertension (OR = 3.7) and underlying immunosuppressant patients receiving corticosteroid therapy (OR = 3.62) in addition to symptoms like anorexia [OR = 2.55] and dyspnea (OR = 6.99) tend to increase the risk of hospital admission in COVID-19 patients, suggesting their predictive values for hospitalization of COVID-19 patients. CONCLUSION: Our results indicated that different factors tend to increase the odds of hospital admission in patients with positive and negative COVID-19 tests, suggesting their predictive values for hospitalization.

Deep Convolutional Neural Network-Based Computer-Aided Detection System for COVID-19 Using Multiple Lung Scans: Design and Implementation Study.

BACKGROUND: Owing to the COVID-19 pandemic and the imminent collapse of health care systems following the exhaustion of financial, hospital, and medicinal resources, the World Health Organization changed the alert level of the COVID-19 pandemic from high to very high. Meanwhile, more cost-effective and precise COVID-19 detection methods are being preferred worldwide. OBJECTIVE: Machine vision-based COVID-19 detection methods, especially deep learning as a diagnostic method in the early stages of the pandemic, have been assigned great importance during the pandemic. This study aimed to design a highly efficient computer-aided detection (CAD) system for COVID-19 by using a neural search architecture network (NASNet)-based algorithm. METHODS: NASNet, a state-of-the-art pretrained convolutional neural network for image feature extraction, was adopted to identify patients with COVID-19 in their early stages of the disease. A local data set, comprising 10,153 computed tomography scans of 190 patients with and 59 without COVID-19 was used. RESULTS: After fitting on the training data set, hyperparameter tuning, and topological alterations of the classifier block, the proposed NASNet-based model was evaluated on the test data set and yielded remarkable results. The proposed model's performance achieved a detection sensitivity, specificity, and accuracy of 0.999, 0.986, and 0.996, respectively. CONCLUSIONS: The proposed model achieved acceptable results in the categorization of 2 data classes. Therefore, a CAD system was designed on the basis of this model for COVID-19 detection using multiple lung computed tomography scans. The system differentiated all COVID-19 cases from non-COVID-19 ones without any error in the application phase. Overall, the proposed deep learning-based CAD system can greatly help radiologists detect COVID-19 in its early stages. During the COVID-19 pandemic, the use of a CAD system as a screening tool would accelerate disease detection and prevent the loss of health care resources.

COVID-19-related coagulopathy: A review of pathophysiology and pharmaceutical management.

December 2019 will never be forgotten in the history of medicine when an outbreak of pneumonia of unknown etiology in Wuhan, China sooner or later prompted the World Health Organization to issue a public health warning emergency. This is not the first nor will it be the last time that a member of ß-coronaviruses (CoVs) is waging a full-scale war against human health. Notwithstanding the fact that pneumonia is the primary symptom of the novel coronavirus (2019nCoV; designated as SARS-CoV-2), the emergence of severe disease mainly due to the injury of nonpulmonary organs at the shadow of coagulopathy leaves no choice, in some cases, rather than a dreadful death. Multiple casual factors such as inflammation, endothelial dysfunction, platelet and complement activation, renin-angiotensin-aldosterone system derangement, and hypoxemia play a major role in the pathogenesis of coagulopathy in coronavirus disease 2019 (COVID-19) patients. Due to the undeniable role of coagulation dysfunction in the initiation of several complications, assessment of coagulation parameters and the platelet count would be beneficial in early diagnosis and also timely prediction of disease severity. Although low-molecular-weight heparin is considered as the first-line of treatment in COVID-19-associated coagulopathy, several possible therapeutic options have also been proposed for better management of the disease. In conclusion, this review would help us to gain insight into the pathogenesis, clinical manifestation, and laboratory findings associated with COVID-19 coagulopathy and would summarize management strategies to alleviate coagulopathy-related complications.

A randomized clinical trial evaluating the immunomodulatory effect of convalescent plasma on COVID-19-related cytokine storm.

Evaluating the effect of convalescent plasma (CP) on some cytokine storm indices in severe COVID-19 patients. Totally, 62 patients were randomly assigned into two groups for this clinical trial. Patients in the intervention group received one unit (500 mL) plasma on the admission day plus standard drugs while the controls merely received standard treatments. Eventually, primary and secondary outcomes were evaluated. In the CP group, compared with controls, the mean levels of lymphocytes and IL-10 significantly increased while the levels of IL-6, TNF-α, and IFN-γ decreased (p < 0.05). The length of in-hospital stay, and mortality rate did not significantly reduce in the CP group compared with controls (p > 0.05) while WHO severity scores remarkably improved (p = 0.01), despite the higher frequency of underlying diseases among the CP group (66.7%) vs. controls (33.3%). Although CP has a remarkable immunomodulatory and antiviral potential to improve the cytokine storm and disease severity in COVID-19 patients, it did not considerably affect the mortality rate.

Ozone therapy for the treatment of COVID-19 pneumonia: A scoping review.

Severe forms of COVID-19 can evolve into pneumonia, featured by acute respiratory failure due to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In viral diseases, the replication of viruses is seemingly stimulated by an imbalance between pro-oxidant and antioxidant activity as well as by the deprivation of antioxidant mechanisms. In COVID-19 pneumonia, oxidative stress also appears to be highly detrimental to lung tissues. Although inhaling ozone (O3) gas has been shown to be toxic to the lungs, recent evidence suggests that its administration via appropriate routes and at small doses can paradoxically induce an adaptive reaction capable of decreasing the endogenous oxidative stress. Ozone therapy is recommended to counter the disruptive effects of severe COVID-19 on lung tissues, especially if administered in early stages of the disease, thereby preventing the progression to ARDS.

A patient affected by critical COVID-19 pneumonia, successfully treated with convalescent plasma.

We present a critically ill patient affected by COVID-19, whose chest computed tomography (CT) scan featured lung consolidations and severe patchy ground-glass opacitie. On day 3 since hospital admission the patient was placed on convalescent plasma treatment. A combined treatment with supportive care, hemoperfusion and convalescent plasma successfully managed to save the patient's life. Convalescent plasma probably contributed to heal this patient and should always be considered in the management of critically ill COVID-19 cases.

The Prognostic Value of Thrombocytopenia in COVID-19 Patients;a Systematic Review and Meta-Analysis

Introduction: Multiple lines of evidence have attested that decreased numbers of platelets may serve as a surrogate marker for poor prognosis in a wide range of infectious diseases. Thus, to provide a well-conceptualized viewpoint demonstrating the prognostic value of thrombocytopenia in COVID-19, we performed a meta-analysis of pertinent literature. Method: The keywords "platelet" OR "thrombocytopenia" AND "COVID-19" OR "coronavirus 2019" OR "2019-nCoV" OR "SARS-CoV-2" were searched in National Library of Medicine Medline/PubMed and Scopus between December 30, 2019, and May 9, 2020 in English without any restriction. The initial search results were first screened by title and abstract, and then full texts of relevant articles representing information on the platelet count (main outcome) with a clinically validated deinAnition of COVID-19 severity were in. A.nally selected. To assess the existence of bias in the included studies, the funnel plot and egger plot along with egger tests were used. Also, the heterogeneity among the included studies was tested using the Chi-square test. Results: The results of our meta-analysis of 19 studies, totaling 3383 COVID-19 patients with 744 (21.9%) severe cases, revealed that non-severe cases have a significantly higher number of platelets and showed that the probability of the emergence of thrombocytopenia is significantly higher in the severe cases with the pooled mean difference of -21.5 (%95 CI: -31.57, -11.43). Conclusion: Decreased number of platelets more commonly associates with severe COVID-19;however, whether the emergence of thrombocytopenia may result in diseases severity or the severity of the disease may decrease platelets, is open to debate.

Laboratory findings in COVID-19 diagnosis and prognosis.

BACKGROUND: Since its first description, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), formerly known as 2019-nCoV, has attracted tremendous attention in a short period of time as the death toll and number of confirmed cases grows unceasingly. METHODS: To provide a better understanding of the importance of abnormal laboratory findings in COVID-19 diagnosis and prognosis, we searched the Scopus, PubMed, and Web of Science medical databases and selected 19 articles (totaling 2988 patients, 484 of whom [16.1%] had severe disease) that reported panels of laboratory examinations in patients with COVID-19. RESULTS: Although in vitro diagnostics, primarily using PCR- and ELISA-based methods, efficiently contribute to the etiological identification of SARS-CoV-2 infection, we suggest that laboratory medicine may also be of significant assistance when differentiating between severe and non-severe COVID-19. CONCLUSION: When we wrote this article, our ability to provide a definitive conclusion may have been adversely affected by some limitations, such as the low sample size, differently applied methods, dissimilar reference ranges, non-synchronized representations of results, and variety of the patients' panels. Despite the limitations, the analysis of the current scientific literature demonstrates the value of laboratory parameters as simple, rapid, and cost-effective biomarkers in COVID-19 patients.

Clinical efficacy of convalescent plasma for treatment of COVID-19 infections: Results of a multicenter clinical study.

Since Dec. 2019 the new coronavirus (SARS-CoV-2) has infected millions and claimed life of several hundred thousand worldwide. However, so far no approved vaccine or drug therapy is available for treatment of virus infection. Convalescent plasma has been considered a potential modality for COVID-19 infection. One hundred eighty-nine COVID-19 positive patients including 115 patients in plasma therapy group and 74 patients in control group, registered in the hospitals with confirmed COVID-19 infection, entered this multi-center clinical study. Comparison of outcomes including all-cause mortality, total hospitalization days and patients' need for intubation between the two patient groups shows that total of 98 (98.2 %) of patients who received convalescent plasma were discharged from hospital which is substantially higher compared to 56 (78.7 %) patients in control group. Length of hospitalization days was significantly lower (9.54 days) in convalescent plasma group compared with that of control group (12.88 days). Only 8 patients (7%) in convalescent plasma group required intubation while that was 20 % in control group. This clinical study provides strong evidence to support the efficacy of convalescent plasma therapy in COVID-19 patients and recommends this treatment for management of these patients. Clinical efficacy, immediate availability and potential cost effectiveness could be considered as main advantages of convalescent plasma therapy.

Management of COVID-19 Virus Infection by Convalescent Plasma.

No Abstract.