Tocilizumab in patients with severe COVID-19: A single-center observational analysis

Patients with coronavirus disease 2019 (COVID-19) may develop severe respiratory distress, thought to be mediated by cytokine release. Elevated proinflammatory markers have been associated with disease severity. Tocilizumab, an interleukin-6 receptor antagonist, may be beneficial for severe COVID-19, when cytokine storm is suspected. This is a retrospective single-center analysis of the records of patients diagnosed with COVID-19 who received tocilizumab. Outcomes, including clinical improvement, mortality and changes in oxygen-support at 24, 48, and 72 hours, and 7, 14, and 28 days post-tocilizumab, are reported. Patients were evaluated by baseline pre-tocilizumab oxygenation status and changes in proinflammatory markers within 7 days post-tocilizumab are reported. Sixty-six patients received tocilizumab at a mean dose of 724 mg (7.4 mg/kg), 3.7 days from admission. At baseline, 53% of patients were on ventilation support and all had elevated proinflammatory markers, including c-reactive protein (CRP). Common comorbidities were diabetes mellitus (43%) and hypertension (74%). Most patients received concomitant glucocorticoids and hydroxychloroquine. Seven days after tocilizumab, ten patients (15.2%) had clinical improvement in their oxygenation status, and there was a 95% decrease in CRP. Within 14 days of treatment, 29% of patients had clinical improvement, 20% had minimal or no improvement, 17% worsened, 27% died, and 7% were transferred to an outside hospital. Ultimately, 42% of all patients that received tocilizumab expired and 49% were discharged. This study found limited clinical improvement in patients that received tocilizumab in the setting of severe COVID-19. Clinical trials are ongoing to further evaluate tocilizumab's benefit in this patient population.     

CCR2 and DPP9 expression in the peripheral blood of COVID-19 patients: Influences of the disease severity and gender

IntroductionHyper-inflammatory reactions play a crucial role in the pathogenesis of the severe forms of COVID-19. However, clarification of the molecular basis of the inflammatory-related factors needs more consideration. The aim was to evaluate the gene expression of two fundamental molecules contributing to the induction of inflammatory like CCR2 and DPP9 in cells from peripheral blood samples from patients with various patterns of COVID-19.MethodsPeripheral blood samples were collected from 470 patients (235 male and 235 female) with RT-qPCR-confirmed COVID-19 test exhibiting moderate, severe, and critical symptoms based on WHO criteria. 100 healthy subjects (50 male and 50 female) were also enrolled in the study as a control group. The gene expression of DPP-9 and CCR-2 was assessed in the blood samples using real-time PCR method.ResultsThe COVID-19 patients in severe stage expressed higher levels of CCR2 and DPP9 compared with healthy controls. In male and female patients, the levels of CCR2 and DDP9 expression significantly differed between moderate, severe, and critical patterns (p < 0.0001) as well as between each COVID-19 form and control group (p < 0.0001). The male patients with severe COVID-19 expressed greater levels of CCR2 and DPP-9 than female with same disease form. The female patients with moderate and critical COVID-19 expressed greater levels of CCR2 and DPP-9 than male patients with same disease stage.ConclusionWe demonstrated that the expression of DPP-9 and CCR-2 was substantially increased in COVID-19 patients with different forms of disease. Considerable differences were also demonstrated between male and female with different patterns of disease. Therefore, we suggest to consider the gender of patients and disease severity for management of COVID-19.     

The impact of COVID-19 on transfusion-dependent thalassemia patients of Karachi,Pakistan: A single-center experience

ObjectivesWith the advent of COVID-19 in Pakistan, the already fragmented blood transfusion services (BTS) received a severe blow, putting the lives of transfusion-dependent thalassemia children on stake. This study aimed to assess the impact of the COVID-19 on blood transfusion therapy (BTT) of thalassemia patients and suggest ways to ensure safe and reliable blood supplies amid such health crises.Material and methodsA retrospective, cross-sectional study was conducted from October 2019 (before COVID-19) to July 2020 (during COVID-19) based on the data provided by a thalassemia center, named Help International Welfare Trust, Karachi, Pakistan. SPSS version 24.0 was used for the data analysis. Data were described in the form of means and percentages.ResultsThere was a significant reduction in the consumption of PRBCs bags after the emergence of COVID-19 (P = 0.002). Moreover, the number of thalassemia patients receiving BTT was dropped by 10.56% during the pandemic. There was a strong negative correlation observed between the rising cases of COVID-19 in Pakistan and the number of patients missing their therapy sessions (r = ?0.914, P = 0.030). A considerable decline in the reserves of all Rhesus-negative blood groups amid the COVID-19 outbreak was also observed.ConclusionThe COVID-19 pandemic adversely affected the already suboptimal care catered to thalassemia patients in Karachi, Pakistan. The fear of the virus contraction coupled with the lockdown and restricted mobility has disrupted the entire transfusion chain from donor to the recipient. Collaborated efforts by the government and healthcare authorities are essential to ensure sufficient blood for thalassemia patients amid the pandemic.     

A novel scoring system for selecting the target patients of COVID-19 convalescent plasma therapy: A hypothesis

The primary cause of mortality in patients of coronavirus disease 2019 (COVID-19) is the cytokine storm and not directly due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Therefore, it is being stressed by transfusion medicine specialists to use COVID-19 convalescent plasma (CCP) therapy early in the course of the disease, preferably within 72 h of diagnosis. The authors herein, propose a scoring system for the rapid assessment of the patients who have tested positive for SARS-CoV-2. Therefore, a systematic approach may be followed where the patients are categorised into two groups, namely, the low-risk group [LRG; score < 5] and the high-risk group [HRG; score ≥ 5] based on this scoring system. Those classified as an HRG should be administered CCP therapy within 72 h of a confirmed diagnosis of COVID-19 to neutralise the SARS-CoV-2 virus and prevent the occurrence of the cytokine storm. This in turn could help reduce the overall mortality in the recipients.     

A sensitive indicator for the severity of COVID-19: thiol

Background/aimThiol status is a good reflector of the cellular redox and have vital roles in various cellular signaling pathways. The purpose of the study was to investigate thiol status in patients with SARS-CoV-2 infection. Materials and methods A total of 587 subjects (517 patients/70 healthy controls) were enrolled in the study.The patients were categorized into the groups regarding to the severity of disease (mild, moderate, severe, and critical).Thiol status of all groups were compared.ResultsThe patients had significantly diminished thiol levels compared to controls. Thiol levels were gradually decreased as the severity of the disease increased. Logistic regression analyses identified that thiol concentrations were an independent risk factor for the disease severity in each phase (mild group OR 0.975, 95%CI 0.965-0.986; moderate group, OR 0.964, 95%CI 0.953-0.976; severe group OR 0.953, 95%CI 0.941-0.965; critical group OR 0.947, 95%CI 0.935-0.960).Thiol test exhibited the largest area under the curve at 0.949, with the highest sensitivity (98.6%) and specificity (80.4%).ConclusionsDepleted thiol status was observed in SARS-CoV-2 infection. Decline of the thiol levels by degrees while the severity of infection increased was closely related to the progression of the disease. This outcome highlights that thiols could be an impressible biomarker for predicting of the severity of COVID-19.     

INR and COVID-19 severity and mortality: A systematic review with meta-analysis and meta-regression

ObjectivesD-dimer elevations, suggesting a pro-thrombotic state and coagulopathy, predict adverse outcomes in coronavirus disease 2019 (COVID-19). However, the clinical significance of other coagulation markers, particularly the international normalized ratio (INR), is not well established. We conducted a systematic review and meta-analysis of the INR in COVID-19.MethodsA literature search was conducted in PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting INR values, measures of COVID-19 severity, and mortality (PROSPERO registration number: CRD42021241468).ResultsThirty-eight studies in 7440 COVID-19 patients with low disease severity or survivor status during follow up (50 ​% males, mean age 57 years) and 2331 with high severity or non-survivor status (60 ​% males, mean age 69 years) were identified. The INR was significantly prolonged in patients with severe disease or non-survivor status than in patients with mild disease or survivor status (standard mean difference, SMD, 0.60; 95 ​% confidence interval, CI 0.42 to 0.77; p ​< ​0.001). There was extreme between-study heterogeneity (I² ​= ​90.2 ​%; p ​< ​0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. The Begg's and Egger's t-tests did not show publication bias. In meta-regression, the SMD of the INR was significantly associated with C-reactive protein (p ​= ​0.048) and D-dimer (p ​= ​0.001).ConclusionsProlonged INR values were significantly associated with COVID-19 severity and mortality. Both INR prolongation and D-dimer elevations can be useful in diagnosing COVID-19-associated coagulopathy and predicting clinical outcomes.     

COVID-19 in Unvaccinated patients with inherited metabolic disorders: A single center experience

Patients with certain inherited metabolic disorders (IMD) are at high risk for metabolic decompensation with exposure to infections. The COVID-19 pandemic has been particularly challenging for health care providers dealing with IMD patients, in view of its unpredictable consequences in these patients. There is limited data in literature on evaluating the impact and the outcome of COVID-19 infection in these patients. This cross-sectional retrospective study on a large cohort of unvaccinated IMD patients, reviewed the incidence of COVID-19 infection, disease manifestation and outcome during the pandemic between November 2019 and July 2021. In this cohort of 1058 patients, 11.7% (n = 124) were infected with COVID-19. Their median age was 16 years (age range 2–42); 57% (n = 71) were males. Post-exposure positive test was noted in 78% (n = 97) patients, while 19% (n = 24) had symptomatic diagnosis and three patients tested positive during pre-hospital visits screening. Most patients, 68.5% (n = 85) had mild COVID-19 related symptoms such as fever, cough, headache and diarrhea while 13.7% (n = 17) patients had no symptoms. Of twenty-two patients (17.7%) who required hospitalization, 16 were adults with various intoxication and energy metabolism disorders, who developed IMD related complications such as metabolic acidosis, hyperammonemia, acute pancreatitis, hypoglycemia, rhabdomyolysis and thrombosis. Ten patients needed intensive care management. The cohort death rate was 2.4% (3 patients).Overall, the clinical course of COVID-19 infection in these IMD patients was relatively mild except for patients with intoxication and energy metabolism disorders who had high risk of developing acute metabolic decompensation with severe complications.     

Tocilizumab treatment in COVID-19: A single center experience

Tocilizumab (TCZ), a monoclonal antibody against interleukin-6 (IL-6), emerged as an alternative treatment for COVID-19 patients with a risk of cytokine storms recently. In the present study, we aimed to discuss the treatment response of TCZ therapy in COVID-19 infected patients. The demographic, treatment, laboratory parameters of C-reactive protein (CRP) and IL-6 before and after TCZ therapy and clinical outcome in the 15 COVID-19 patients were retrospectively assessed. Totally 15 patients with COVID-19 were included in this study. Two of them were moderately ill, six were seriously ill and seven were critically ill. The TCZ was used in combination with methylprednisolone in eight patients. Five patients received the TCZ administration twice or more. Although TCZ treatment ameliorated the increased CRP in all patients rapidly, for the four critically ill patients who received an only single dose of TCZ, three of them (No. 1, 2, and 3) still dead and the CRP level in the rest one patient (No. 7) failed to return to normal range with a clinical outcome of disease aggravation. Serum IL-6 level tended to further spiked firstly and then decreased after TCZ therapy in 10 patients. A persistent and dramatic increase of IL-6 was observed in these four patients who failed treatment. TCZ appears to be an effective treatment option in COVID-19 patients with a risk of cytokine storms. And for these critically ill patients with elevated IL-6, the repeated dose of the TCZ is recommended.     

Effects of COVID-19 on children with autism

The coronavirus disease 2019 (COVID-19) pandemic affects all countries and populations worldwide, significantly impacting people with autism with a high risk of morbidity and mortality due to COVID-19. Approximately 25% of children with autism have an asymptomatic or symptomatic immune deficiency or dysfunction. In addition, they frequently have various comorbid conditions that increase the severity of COVID-19. In addition, severe COVID-19 during pregnancy may increase the risk of autism in the offspring. Furthermore, severe acute respiratory syndrome coronavirus 2 could target human nervous system tissues due to its neurotrophic effects. The COVID-19 pandemic intensely impacts many patients and families in the autism community, especially the complex management of autism-associated disorders during the complete lockdown. During the complete lockdown, children with autism had difficulties coping with the change in their routine, lack of access to special education services, limited physical space available, and problems related to food and sleep. Additionally, children with autism or intellectual disabilities are more liable to be abused by others during the pandemic when the standard community supports are no longer functioning to protect them. Early detection and vaccination of children with autism against COVID-19 are highly indicated. They should be prioritized for testing, vaccination, and proper management of COVID-19 and other infectious diseases. In this review, we discuss the various effects of COVID-19 on children with autism, the difficulties they face, the increased risk of infection during pregnancy, how to alleviate the impact of COVID-19, and how to correct the inequalities in children with autism.     

COVID-19 Vaccination Rates in Patients With Chronic Medical Conditions: A Nationwide Cross-Sectional Study

As most individuals acquire immunity to severe acute respiratory syndrome coronavirus 2, South Korea declared a return to normalcy a few months ago. However, epidemic waves continue because of endlessly emerging variants and waning immunity. Health authorities are focusing on those at high risk of severe coronavirus disease 2019 to minimize damage to public health and the economy. In this regard, we investigated the vaccination rates in patients with various chronic medical conditions by examining the national health insurance claims data and the national immunization registry. We found that patients with chronic medical conditions, especially those of higher severity, such as malignancy, had vaccination rates approximately 10–20% lower than those of the general population. Public health authorities and healthcare providers should try to vaccinate these patients to avoid preventable morbidity and mortality.     

Serum CK-MB,COVID-19 severity and mortality: An updated systematic review and meta-analysis with meta-regression

ObjectivesWe conducted a systematic review and meta-analysis with meta-regression of creatine kinase-MB (CK-MB), a biomarker of myocardial injury, in COVID-19 patients.MethodsWe searched PubMed, Web of Science and Scopus, for studies published between January 2020 and January 2021 that reported CK-MB, COVID-19 severity and mortality (PROSPERO registration number: CRD42021239657).ResultsFifty-five studies in 11,791 COVID-19 patients were included in the meta-analysis. The pooled results showed that CK-MB concentrations were significantly higher in patients with high disease severity or non-survivor status than patients with low severity or survivor status (standardized mean difference, SMD, 0.81, 95% CI 0.61 to 1.01, p<0.001). The rate of patients with CK-MB values above the normal range was also significantly higher in the former than the latter (60/350 vs 98/1,780; RR ​= ​2.84, 95%CI 1.89 to 4.27, p<0.001; I² ​= ​19.9, p ​= ​0.254). Extreme between-study heterogeneity was observed (I² ​= ​93.4%, p<0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified (effect size range, 0.77 to 0.84). Begg's (p ​= ​0.50) and Egger's (p ​= ​0.86) t-tests did not show publication bias. In meta-regression analysis, the SMD was significantly and positively associated with the white blood count, aspartate aminotransferase, myoglobin, troponin, brain natriuretic peptide, lactate dehydrogenase, and D-dimer.ConclusionsHigher CK-MB concentrations were significantly associated with severe disease and mortality in COVID-19 patients. This biomarker of myocardial injury might be useful for risk stratification in this group.     

Association of echocardiographic parameters with chest computed tomography score in patients with COVID-19 disease

PurposeAlthough coronavirus disease 2019 (COVID-19) primarily affects the pulmonary system, the involvement of the heart has become a well-known issue. Pulmonary CT plays an additive role in the diagnosis and prognosis of the disease. We aimed to investigate the association of echocardiographic indices with pulmonary CT scores and mortality in COVID-19 patients.Materials and methodsA total of 123 patients diagnosed with COVID-19 were included in this study. The British Society of Thoracic Imaging (BSTI) score and echocardiographic parameters were calculated, and echocardiographic indices were compared between BSTI score grades.ResultsDuring in-hospital follow-up, 36 of 123 patients (29.3%) had died. BSTI score, IVS, LVPWd, RV mid-diameter, RV basal diameter, RV longitudinal diameter, sPAP, and RVMPI were higher, and RVFAC, TAPSE, and RVS were lower in the non-survivor group than in the survivor group. There were statistically significant changes between BSTI scores in terms of LVPWd, RV mid diameter, RV basal diameter, RV longitudinal diameter, sPAP, RVFAC, RVMPI, and TAPSE. BSTI score was positively correlated with sPAP and RV basal diameter and negatively correlated with TAPSE and RVFAC. Multivariate logistic regression analysis demonstrated that sPAP (OR ​= ​1.071, p ​= ​0.002) and RV basal diameter (OR ​= ​1.184, p ​= ​0.005) were independent predictors of high BSTI scores (grade 4 and 5). Furthermore, age, sPAP, and a high BSTI score (grade 5) were independent predictors of in-hospital mortality in COVID-19 patients.ConclusionEchocardiographic indices were correlated with BSTI scores, and patients with higher BSTI scores had more cardiac involvement in COVID-19.     

COVID-19 epidemic: Disease characteristics in children

In mid-December 2019, a disease caused by infection with severe acute respiratory syndrome coronavirus-2, which began in Wuhan, China, has spread throughout the country and many countries around the world. The number of children with coronavirus disease-2019 (COVID-19) has also increased significantly. Although information regarding the epidemiology of COVID-19 in children has accumulated, relevant comprehensive reports are lacking. The present article reviews the epidemiological characteristics of COVID-19 in children.     

Longitudinal neutralizing antibody responses after SARS-CoV-2 infection: A convalescent cohort study in Taiwan

BackgroundUnderstanding the neutralizing antibody (NAb) titer against COVID-19 over time is important to provide information for vaccine implementation. The longitudinal NAb titer over one year after SARS-CoV-2 infection is still unclear. The purposes of this study are to evaluate the duration of the neutralizing NAb titers in COVID-19 convalescents and factors associated with the titer positive duration.MethodsA cohort study followed COVID-19 individuals diagnosed between 2020 and 2021 May 15th from the COVID-19 database from the Taiwan Centers for Disease Control. We analyzed NAb titers from convalescent SARS-CoV-2 individuals. We used generalized estimating equations (GEE) and a Cox regression model to summarize the factors associated with NAb titers against COVID-19 decaying in the vaccine-free population.ResultsA total of 203 convalescent subjects with 297 analytic samples were followed for a period of up to 588 days. Our study suggests that convalescent COVID-19 in individuals after more than a year and four months pertains to only 25% of positive titers. The GEE model indicates that longer follow-up duration was associated with a significantly lower NAb titer. The Cox regression model indicated the disease severity with advanced condition was associated with maintaining NAb titers (adjusted hazard ratio: 2.01, 95% CI: 1.11–3.63) and that smoking was also associated with higher risk of negative NAb titers (adjusted hazard ratio: 0.55, 95% CI: 0.33–0.92).ConclusionsNeutralizing antibody titers diminished after more than a year. The antibody titer response against SARS-CoV-2 in naturally convalescent individuals provides a reference for vaccinations.     

Risk factors for severe and critically ill COVID-19 patients: A review

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1β, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.     

Risk Factors for Severe COVID-19 in Children: A Systematic Review and Meta-Analysis

BackgroundCoronavirus disease 2019 (COVID-19) has been the most important global issue since December 2019. Although the clinical course of COVID-19 is known to be milder in children than in adults, associated hospitalizations among children have increased since the emergence of contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the achievement of a high vaccination rate in adults. Considering these global and domestic situations, we believe that risk stratification in children with COVID-19 is urgently needed for decision making regarding hospitalization priority in children infected with SARS-CoV-2 and vaccination priority against COVID-19.MethodsThis systematic review and meta-analysis was performed by comprehensively searching the PubMed, EMBASE, Scopus and KoreaMed databases through August 25, 2021. The criteria for enrollment were “severe COVID-19” as poor outcomes (intensive care unit admission, invasive mechanical ventilation, and/or death) and underlying comorbidities before SARS-CoV-2 infection.ResultsAmong 872 screened studies, 17 articles were included in the systematic review, and 10 articles were included in the meta-analysis. Neonate (risk ratio [RR], 2.69; 95% confidence interval [CI], 1.83–3.97), prematurity in young infants (RR, 2.00; 95% CI, 1.63–2.46), obesity (RR, 1.43; 95% CI, 1.24–1.64), diabetes (RR, 2.26; 95% CI, 1.95–2.62), chronic lung disease (RR, 2.62; 95% CI, 1.71–4.00), heart disease (RR, 1.82; 95% CI, 1.58–2.09), neurologic disease (RR, 1.18; 95% CI, 1.05–1.33), and immunocompromised status (RR, 1.44; 95% CI, 1.01–2.04) were significant risk factors for severe COVID-19 in children. In the subgroup analysis, age younger than 3 months (RR, 0.26; 95% CI, 0.11–0.66), asthma (RR, 1.08; 95% CI, 0.98–1.20), and neurodevelopmental disorders (RR, 0.88; 95% CI, 0.75–1.04) were not risk factors for severe COVID-19.ConclusionChildren with comorbidities such as obesity, diabetes, heart disease, chronic lung diseases other than asthma, seizure disorders, and an immunocompromised status had a high prevalence of severe COVID-19. Neonate and premature infants had a high risk of severe COVID-19. Defining the high-risk group for severe COVID-19 could help to guide hospital admission and priority for vaccination against SARS-CoV-2.