Prognostic Indicators for Severity in COVID-19 Patients:a Meta-analysis

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play a crucial role in the context of viral infections and their associated diseases. The link between HSCs and HPCs and disease status in COVID-19 patients is largely unknown. This study aimed to monitor the kinetics and contributions of HSCs and HPCs in severe and non-severe COVID-19 patients and to evaluate their diagnostic performance in differentiating between healthy and COVID-19 patients as well as severe and non-severe cases. Peripheral blood (PB) samples were collected from 48 COVID-19 patients, 16 recovered, and 27 healthy controls and subjected to deep flow cytometric analysis to determine HSCs and progenitor cells. Their diagnostic value and correlation with C-reactive protein (CRP), D-dimer, and ferritin levels were determined. The percentages of HSCs and common myeloid progenitors (CMPs) declined significantly, while the percentage of multipotent progenitors (MPPs) increased significantly in COVID-19 patients. There were no significant differences in the percentages of megakaryocyte-erythroid progenitors (MEPs) and granulocyte-macrophage progenitors (GMPs) between all groups. Severe COVID-19 patients had a significantly low percentage of HSCs, CMPs, and GMPs compared to non-severe cases. Contrarily, the levels of CRP, D-dimer, and ferritin increased significantly in severe COVID-19 patients. MPPs and CMPs showed excellent diagnostic performance in distinguishing COVID-19 patients from healthy controls and severe from non-severe COVID-19 patients, respectively. Collectively, our study indicated that hematopoietic stem and progenitor cells are significantly altered by COVID-19 and could be used as therapeutic targets and diagnostic biomarkers for severe COVID-19.

BackgroundThe hematological abnormalities are assumed to be involved in the disease progression of COVID-19. However, the actual associations between specific blood parameters and COVID-19 are not well understood. Here we aimed to assess the correlations between hematological parameters and the severity of COVID-19.MethodsWe included COVID-19 patients who were admitted to Evercare Hospital Ltd, Dhaka, Bangladesh, between November 10, 2020, to April 12, 2021, with a confirmed case of RT-PCR test. We recorded demographic information, clinical data, and routine hematological examination results of all COVID-19 patients. We performed statistical analyses and interpretation of data to compare severe COVID-19 patients (SCP) and non-severe COVID-19 patients (NSCP).ResultsThe age and BMI of the admitted COVID-19 patients were 48.79±8.53 years and 25.82±3.75 kg/m2. This study included a total of 306 hospitalized COVID-19 patients. Among them, NSCP and SCP were 198 and 108, respectively. And we recorded 12 deaths from SCP. We observed the alterations of several hematological parameters between SCP and NSCP. Among them, we noticed the increased levels of C-reactive protein (CRP), d-dimer, and ferritin showed good indicative value to evaluate the severity of COVID-19. Also, there were positive correlations among these parameters. Moreover, we found correlations between the outcomes of COVID-19 patients with patient’s demographics and comorbid diseases.ConclusionBased on our results, CRP, d-dimer, and ferritin levels at admission to hospitals represent simple assessment factors for COVID-19 severity and the treatment decisions at the hospital setup. These blood parameters could serve as indicators for the prognosis and severity of COVID-19. Therefore, our study findings might help to develop a treatment protocol for COVID-19 patients at the hospital setup.

The hematological abnormalities are assumed to be involved in the disease progression of COVID-19. However, the actual associations between specific blood parameters and COVID-19 are not well understood. Here we aimed to assess the correlations between hematological parameters and the severity of COVID-19. We included COVID-19 patients who were admitted to Evercare Hospital Ltd, Dhaka, Bangladesh, between November 10, 2020, to April 12, 2021, with a confirmed case of RT-PCR test. We recorded demographic information, clinical data, and routine hematological examination results of all COVID-19 patients. We performed statistical analyses and interpretation of data to compare severe COVID-19 patients (SCP) and non-severe COVID-19 patients (NSCP). The age and BMI of the admitted COVID-19 patients were 48.79±8.53 years and 25.82±3.75 kg/m2. This study included a total of 306 hospitalized COVID-19 patients. Among them, NSCP and SCP were 198 and 108, respectively. And we recorded 12 deaths from SCP. We observed the alterations of several hematological parameters between SCP and NSCP. Among them, we noticed the increased levels of C-reactive protein (CRP), d-dimer, and ferritin showed good indicative value to evaluate the severity of COVID-19. Also, there were positive correlations among these parameters. Moreover, we found correlations between the outcomes of COVID-19 patients with patient's demographics and comorbid diseases. Based on our results, CRP, d-dimer, and ferritin levels at admission to hospitals represent simple assessment factors for COVID-19 severity and the treatment decisions at the hospital setup. These blood parameters could serve as indicators for the prognosis and severity of COVID-19. Therefore, our study findings might help to develop a treatment protocol for COVID-19 patients at the hospital setup.

Risk factors for severe COVID-19: Evidence from 167 hospitalized patients in Anhui, China

Hyperglycemia associated with lymphopenia and disease severity of COVID-19 in type 2 diabetes mellitus

The recently emerged novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has posed a serious threat to public health, and there is an urgent need to establish tools that can aid the clinician in the evaluation and management of highrisk patients. This meta-analysis aimed to investigate the potential of sACE2 (soluble angiotensinconverting enzyme 2) as a prognostic biomarker in COVID-19. A comprehensive search of PubMed/MEDLINE, Cochrane, and Google Scholar, was performed until May 26, 2021. Data extraction and quality assessment of the study were independently conducted by the authors. Finally, 6 studies were included in this meta-analysis. ACE-2 serum or plasma levels were compared between COVID-19 patients and healthy controls. ACE-2 level was not significantly different between severe COVID-19 patients and healthy controls (SMD = 1.2; 95% CI: -1.3-1.5; P = 0.86), severe and non-severe COVID-19 patients (SMD = 0.3; 95% CI: -0.06-0.7; P = 0.1), and severe COVID-19 patients and healthy controls (SMD = 0.6; 95% CI: -1.1-2.3; P = 0.5). We cautiously propose that circulating levels of ACE2 cannot be used as a biomarker to assess disease severity in COVID-19 patients.

Aim: The study aimed to assess the relationships between serum cytokine levels and pulmonary dysfunctions in individuals with COVID-19. These correlations may help to suggest strategies for prevention and therapies of coronavirus disease. Patients and methods: Fifty healthy participants and one hundred COVID-19 patients participated in this study. COVID-19 participants were subdivided into moderate and severe groups based on the severity of their symptoms. In both patients and healthy controls, white blood cells (WBCs) and lymphocytes counts and serum C-reactive protein (CRP), interleukin (IL)-1, IL-4, IL-6, IL-18, and IL-35 levels were estimated. All the patients were examined by chest computed tomography (CT) and the COVID-19 Reporting and Data System (CO-RADS) score was assessed. Results: All COVID-19 patients had increased WBCs count and CRP, IL-1β, IL-4, IL-6, IL-18, and IL-35 serum levels than healthy controls. Whereas WBCs, CRP, and cytokines like IL-6 showed significantly higher levels in the severe group as compared to moderate patients, IL-4, IL-35, and IL-18 showed comparable levels in both disease groups. Lymphocytes count in all patient groups exhibited a significant decrease as compared to the heathy controls and it was significantly lower in severe COVID-19 than moderate. Furthermore, CO-RADS score was positively connected with WBCs count as well as CRP and cytokine (IL-35, IL-18, IL-6, IL-4 and IL-1β) levels in both groups. CO-RADS score, also demonstrated a positive correlation with lymphocytes count in the moderate COVID-19 patients, whereas it demonstrated a negative correlation in the severe patients. The receiver operator characteristic (ROC) curve analysis indicated that IL-1β, IL-4, IL-18, and IL-35 were fair (acceptable) predictors for COVID-19 in moderate cases. Whereas IL-6 was good predictor of COVID-19 in severe cases (AUC > 0.800), IL-18 and IL-35 were fair. Conclusion: Severe COVID-19 patients, compared to individuals with moderate illness and healthy controls, had lower lymphocyte counts and increased CRP with greater WBCs counts. In contrast to moderate COVID-19 patients, severe COVID-19 patients had higher levels of IL-6, but IL-4, IL-18, and IL-35 between both illness categories were at close levels. IL-6 level was the most potent predictor of COVID-19 progress and severity. CO-RADS 5 was the most frequent category in both moderate and severe cases. Patients with a typical CO-RADS involvement had a higher CRP and cytokine (IL-1β, IL-6, IL-4, IL-18, and IL-35) levels and WBCs count with a lower lymphocyte number than the others. Cytokine and CRP levels as well as WBCs and lymphocyte counts were considered surrogate markers of severe lung affection and pneumonia in COVID 19 patients.

There is an urgent need for effective treatment and preventive vaccine to contain this devastating global pandemic, which requires a comprehensive understanding of humoral responses specific to SARS-CoV-2 during the disease progression and convalescent phase of COVID-19 patients. We continuously monitored the serum IgM and IgG responses specific to four SARS-CoV-2 related antigens, including the nucleoprotein (NP), receptor binding domain (RBD), S1 protein, and ectodomain (ECD) of the spike protein among non-severe and severe COVID-19 patients for seven weeks since disease onset. Most patients generated humoral responses against NP and spike protein-related antigens but with their distinct kinetics profiles. Combined detection of NP and ECD antigens as detecting antigen synergistically improved the sensitivity of the serological assay, compared to that of using NP or RBD as detection antigen. 80.7% of convalescent sera from COVID-19 patients revealed that the varying extents of neutralization activities against SARS-CoV-2. S1-specific and ECD-specific IgA responses were strongly correlated with the neutralization activities in non-severe patients, but not in severe patients. Moreover, the neutralizing activities of the convalescent sera were shown to significantly decline during the period between 21 days to 28 days after hospital discharge, accompanied by a substantial drop in RBD-specific IgA response. Our data provide evidence that are crucial for serological testing, antibody-based intervention, and vaccine design of COVID-19.

The pandemic of coronavirus disease (Covid-19) has infected millions of individuals around the globe. The current study was aimed to evaluate the serum procalcitonin (PCT) level as a biomarker for bacterial co-infection and disease severity in Covid-19 patients. A total of 319 Covid-19 positive patients were examined in this study. Among the total individuals, 169 (53%) were male while 150 (47%) were female. Among the examined samples, 142 (44.5%) were hospitalized in Covid services, and 177(55.5%) were admitted in the intensive care unit (ICU). The mean PCT level for Covid-19 services patients was 0.58 ng/mL and for ICU patients was 7.84 ng/mL. The statistical analysis revealed that there was a significant association of PCT value and age (P<0,0001) while there was no association of gender and PCT value in COVID-19 patients (P=0.2745). Most Covid-19 patients have low PCT levels but elevated markers of inflammation such as C-reactive protein (CRP) on admission. It can be concluded that the serial PCT measurement could determine the prognosis of disease and presence of bacterial co-infection in Covid-19 patients. The main objective of our study is to determine the role of serum procalcitonin in the diagnosis and clinical management of patients with COVID-19 from Oriental Region of Morocco, also we evaluate the correlation between Procalcitonin and disease severity in COVID-19. We report the experience of the Moroccan Mohammed VI University Hospital of Oujda.

Background: Krebs von den Lungen-6 (KL-6) has been proposed as a disease severity marker of COVID-19. All research articles reported the KL-6 assay detected through Fujirebio reagents by Lumipulse G600/G1200 instrument. In the present study, KL-6 assay was analysed through Tosoh AIA-360 and compared with analytical results by Lumipulse G600 in a population of COVID-19 patients. Materials and methods: Sixty-four patients (median age, IQR 67 (58–76) years), all hospitalized for COVID-19 interstitial pneumonia at Siena COVID Unit. KL-6 was measured by two methods, chemiluminescence enzyme immunoassay (CLEIA) and fluorescent enzyme immunoassay (FEIA) method by Lumipulse G600 II and AIA 360 systems, respectively. Results: KL-6 concentrations evaluated by Lumipulse G600II were significantly higher in severe than those in non-severe patients (p < 0.0001) as well as evaluating by AIA360 (p < 0.0001). Receiver operating curve (ROC) curve analysis showed that KL-6 concentrations, by Lumipuse G600II, distinguished severe from non-severe COVID-19 patients with an area under the curve (AUC) of 99.8% and the best cut-off value was 448 U/mL. AUROC between severe and non-severe COVID-19 patients using T0 KL-6 concentrations by AIA360 was 97.4% and the best cut-off value was 398 U/mL. According to T0 KL-6 concentrations in COVID-19 patients, Bland–Altman difference analysis revealed a mean bias of 78 ± 174.8; while using T1 KL-6 concentrations in COVID-19 patients, Bland–Altman difference analysis revealed a mean bias of 48 ± 126 (95% limits of agreement −199–295) between the Lumipulse G600 II and the AIA360 systems. Conclusions: In conclusion, our study demonstrated that CLEIA and FEIA methods for serum KL-6 detection are comparable and reliable. KL-6 was confirmed as an easily detectable and effective biomarker to identify severe COVID-19 patients.

Introduction: The COVID-19 pandemic has had a significant impact on global health, resulting in more than 6 million reported deaths worldwide as of April 2023. This study aimed to investigate the potential of C-reactive protein (CRP), procalcitonin (PCT), and D-dimer as biomarkers for assessing disease severity in COVID-19 patients in Kinshasa, Democratic Republic of Congo Methods:A retrospective examination was conducted involving 339 COVID-19 patients admitted to Kinshasa hospitals between January 2021 and March 2022. CRP, PCT, and D-dimer levels were measured in all patients and compared between those with severe and non-severe illnesses. Results: Our findings revealed significantly higher CRP, PCT, and D-dimer levels in severe cases compared to non-severe cases. Specifically, the median CRP level was 120.6 mg/L in severe cases, 47.3 mg/L in mild cases, and 13.5 mg/L in moderate cases. The median PCT levels were 0.26 ng/mL in severe cases, 0.08 ng/ mL in mild cases, and 0.07 ng/L in moderate cases. Additionally, the median D-dimer level was 1836.9 µg/L in severe cases and 597.6 µg/L in mild cases, with a value of 481.1 µg/L in moderate cases. System learning techniques were also employed to predict disease severity based on these biomarkers, achieving high accuracy. Conclusion: Our findings suggest that CRP, PCT, and D-dimer serve as valuable biomarkers for identifying severe COVID-19 cases in Kinshasa. Furthermore, the application of machine learning methods can yield accurate predictions of disease severity based on these biomarkers. These biomarkers hold the potential to assist clinicians in informed decision-making regarding patient management and contribute to improved clinical outcomes for COVID-19 patients.

BackgroundCOVID-19 infection is associated with a hypercoagulable state. Severe COVID-19 patients present with high plasma fibrinogen levels, continuous deposition of fibrin and the presence of microthrombi in their lungs, accompanied by significant fibrinolysis, resulting in high D-dimer levels. Due to the role of FXIII in fibrin crosslinking and clot stabilization, we analyzed its activity levels and dynamics in COVID-19 patients hospitalized in the intensive care unit (ICU).MethodsFXIII levels were measured in thirty four COVID-19 patients hospitalized in the ICU and in fourteen non-severe COVID-19 patients. FVIII levels were measured for comparison. Laboratory data and clinical variables were recorded.ResultsThe average FXIII activity level in 34 ICU hospitalized COVID-19 patients was 69.9±33 %, significantly lower compared to an average of 120±20.9 % FXIII activity in 14 non-severe COVID-19 patients. FXIII activity levels were below the low normal value (< 79 % FXIII activity) in 74 % of the ICU hospitalized COVID-19 patients. In contrast, high FVIII activity was measured among all severe COVID-19 patients. Consecutive measurements, performed in fourteen ICU hospitalized COVID-19 patients, pointed to a significant decrease in FXIII activity from the average of 85.7±28.2 %, (which is in the normal range), to an average of 68.0±20.4 %, below the low normal range, within 6.4±3.4 days of ICU hospitalization. Liver functions did not differentiate between patients with low and normal FXIII activity. No inhibitor to FXIII activity was found in the plasma of severe COVID-19 patients. Levels of FXIII-A antigen correlated with FXIII activity, and were low in severe COVID-19 patients.ConclusionsLow FXIII activity levels were found in COVID-19 patients hospitalized in the ICU, with gradual decline during their hospitalization. A mechanism of consumption may account for the low FXIII activity in these patients.

COVID-19 patients suffer from the lack of curative therapy. Hence, there is an urgent need to try repurposed old drugs on COVID-19. Randomized controlled study on 70 COVID-19 patients (48 mild-moderate, 11 severe, and 11 critical patients) treated with 200 µg/kg PO of Ivermectin per day for 2-3 days along with 100 mg PO doxycycline twice per day for 5-10 days plus standard therapy; the second arm is 70 COVID-19 patients (48 mild-moderate and 22 severe and zero critical patients) on standard therapy, which is (vitamin C, D, and zinc, azithromycin, dexamethasone and oxygen supply if needed). The time to recovery, the progression of the disease, and the mortality rate were the outcome-assessing parameters. Among all patients and among severe patients, 3/70 (4.28%) and 1/11 (9%), respectively progressed to a more advanced stage of the disease in the Ivermectin-Doxycycline group versus 7/70 (10%) and 7/22 (31.81%), respectively in the control group (P&gt;0.05). The mortality rate was 0/48 (0%), 0/11 (0%), and 2/11 (18.2%) in mild-moderate, severe, and critical COVID-19 patients, respectively in Ivermectin-Doxycycline group versus 0/48 (0%), and 6/22 (27.27%) in mild-moderate and severe COVID-19 patients, respectively in standard therapy group (p=0.052). Moreover, the mean time to recovery was 6.34, 20.27, and 24.13 days in mild-moderate, severe, and critical COVID-19 patients, respectively in Ivermectin-Doxycycline group versus 13.66 and 24.25 days in mild-moderate and severe COVID-19 patients, respectively in standard therapy group (P&lt;0.01). It is concluded that Ivermectin with doxycycline reduced the time to recovery, the percentage of patients progress to more advanced stage of disease, and reduced mortality rate in severe patients from 22.72% to 0%. Keywords: Ivermectin, Doxycycline, COVID-19, Coronavirus, SARS-CoV-2 Citation: Hashim HA, Maulood MF, Ali CL, Rasheed AM, Fatak DF, Kabah KK, Abdulamir AS. Controlled randomized clinical trial on using ivermectin with doxycycline for treating COVID-19 patients in Baghdad, Iraq Iraqi JMS. 2021; 19(1): 107-115. doi: 10.22578/IJMS.19.1.14

This study aimed to examine the relationship between Hb A1c levels and the clinical course of coronavirus-19 (COVID-19) patients. Sixty-six COVID-19(+) patients with high Hb A1c and 46 with average Hb A1c and 30 COVID-19(–) patients with average Hb A1c were included. Hb A1c levels and parameters examined in COVID-19(+) patients were compared between groups, and correlation analysis was performed between these parameters and Hb A1c levels. The effect of Hb A1c levels on intensive care unit (ICU) admission and mortality rate in COVID-19 patients was analyzed with the χ2 test. It was observed that hemoglobin (Hb) and arterial oxygen saturation (SaO2) levels of the COVID-19 (+) groups was lower than the COVID-19 (–) group, while ferritin, D-dimer, procalcitonin (PCT), and C-reactive protein (CRP) levels were higher. The COVID-19 (+) group with high Hb A1c had higher lactate dehydrogenase (LDH), PCT and D-dimer levels than the other two groups, while Hb, partial arterial oxygen pressure (PaO2) levels were lower. The Hb A1c levels of the COVID-19 (+) groups were positively correlated with absolute neutrophil count (ANC), LDH, PCT and (K+) levels, while negatively correlated with Hb and PaO2 levels. Hb A1c was found to be associated with the inflammation process, coagulation disorders and low PaO2 in COVID-19 patients. The COVID-19 patients with high Hb A1c levels had a higher mortality rate than other COVID-19 patients. Using Hb A1c measurements with other prognostic markers would contribute to the patient’s risk of death assessment.

This research aimed to compare albumin, creatinine, and lactate dehydrogenase levels in patients with non-severe and severe covid-19 infections. This investigation was conducted at Babylon provincial hospitals and private laboratories labs from October 2020 to December 2021. The research included 30 patients with covid-19 infection, divided into two groups. Each group contains 15 patients depending on infection severity. The serum samples were separated and stored at −20°C until the lactate dehydrogenase, creatinine, and albumin biological tests were performed. The outcomes revealed a substantial decrease (P≤0.05) in albumin levels in severe Covid-19 patients (34.976±3.17) compared to non-severe Covid-19 patients (40±14.765). Also, a considerable increase was observed (P≤0.05) in creatinine levels in severe Covid-19 patients (1.16±0.45) compared to non-severe Covid-19 patients (0.82±0.53). Finally, crucial elevation (P≤0.05) in lactate dehydrogenase level of severe Covid-19 patients (913.27±213.16) compared to the group of non-severe Covid-19 patients (1437.27±251.27). Lactate dehydrogenase, creatinine, and albumin are employed as medical markers in severe covid-19 infection.