Adult Patients with Cancer Have Impaired Humoral Responses to Complete and Booster COVID-19 Vaccination, Especially Those with Hematologic Cancer on Active Treatment: A Systematic Review and Meta-Analysis.

The exclusion of patients with cancer in clinical trials evaluating COVID-19 vaccine efficacy and safety, in combination with the high rate of severe infections, highlights the need for optimizing vaccination strategies. The aim of this study was to perform a systematic review and meta-analysis of the published available data from prospective and retrospective cohort studies that included patients with either solid or hematological malignancies according to the PRISMA Guidelines. A literature search was performed in the following databases: Medline (Pubmed), Scopus, Clinicaltrials.gov, EMBASE, CENTRAL and Google Scholar. Overall, 70 studies were included for the first and second vaccine dose and 60 studies for the third dose. The Effect Size (ES) of the seroconversion rate after the first dose was 0.41 (95%CI: 0.33-0.50) for hematological malignancies and 0.56 (95%CI: 0.47-0.64) for solid tumors. The seroconversion rates after the second dose were 0.62 (95%CI: 0.57-0.67) for hematological malignancies and 0.88 (95%CI: 0.82-0.93) for solid tumors. After the third dose, the ES for seroconversion was estimated at 0.63 (95%CI: 0.54-0.72) for hematological cancer and 0.88 (95%CI: 0.75-0.97) for solid tumors. A subgroup analysis was performed to evaluate potential factors affecting immune response. Production of anti-SARS-CoV-2 antibodies was found to be more affected in patients with hematological malignancies, which was attributed to the type of malignancy and treatment with monoclonal antibodies according to the subgroup analyses. Overall, this study highlights that patients with cancer present suboptimal humoral responses after COVID-19 vaccination. Several factors including timing of vaccination in relevance with active therapy, type of therapy, and type of cancer should be considered throughout the immunization process.

Domestic Violence During the COVID-19 Pandemic: A Systematic Review.

BACKGROUND: COVID-19 outbreak and the followed confinement measures have raised concerns to specialists worldwide regarding the imminent increase in domestic violence cases. The present systematic review aims to identify the international trends in domestic violence during the COVID-19 epidemic and to examine the possible differences among all population groups and different geographic areas worldwide. METHOD: The following databases were accessed: DOAJ, ERIC, Google Scholar, ProQuest, Pubmed, PsycNet, and SCOPUS, up to July 22, 2020. RESULTS: A total of 32 studies were considered eligible. Data from North America, Europe, Asia-Pacific Area, Africa, and worldwide researches were retrieved. COVID-19 has caused an increase in domestic violence cases, especially during the first week of the COVID-19 lockdown in each country. In children, however, although the specialists' estimations suggested an increase in child maltreatment and abuse cases, the rate of police and social services' reports has declined during the COVID-19 pandemic. School closures that isolated students at home seemed to have contributed to this decrease. CONCLUSIONS: Domestic violence has been a considerable issue imposed by the COVID-19 epidemic to a worldwide context. The home confinement led to constant contact between perpetrators and victims, resulting in increased violence and decreased reports. In order to minimize such issues, prevention measures and supporting programs are necessary.

Convalescent Plasma Therapy for COVID-19: A Systematic Review and Meta-Analysis on Randomized Controlled Trials.

Background: While passive immunotherapy has been considered beneficial for patients with severe respiratory viral infections, the treatment of COVID-19 cases with convalescent plasma produced mixed results. Thus, there is a lack of certainty and consensus regarding its effectiveness. This meta-analysis aims to assess the role of convalescent plasma treatment on the clinical outcomes of COVID-19 patients enrolled in randomized controlled trials (RCTs). Methods: A systematic search was conducted in the PubMed database (end-of-search: 29 December 2022) for RCTs on convalescent plasma therapy compared to supportive care\standard of care. Pooled relative risk (RR) and 95% confidence intervals were calculated with random-effects models. Subgroup and meta-regression analyses were also performed, in order to address heterogeneity and examine any potential association between the factors that varied, and the outcomes reported. The present meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 34 studies were included in the meta-analysis. Per overall analysis, convalescent plasma treatment was not associated with lower 28-day mortality [RR = 0.98, 95% CI (0.91, 1.06)] or improved 28-day secondary outcomes, such as hospital discharge [RR = 1.00, 95% CI (0.97, 1.03)], ICU-related or score-related outcomes, with effect estimates of RR = 1.00, 95% CI (0.98, 1.05) and RR = 1.06, 95% CI (0.95, 1.17), respectively. However, COVID-19 outpatients treated with convalescent plasma had a 26% less risk of requiring hospital care, when compared to those treated with the standard of care [RR = 0.74, 95% CI (0.56, 0.99)]. Regarding subgroup analyses, COVID-19 patients treated with convalescent plasma had an 8% lower risk of ICU-related disease progression when compared to those treated with the standard of care (with or without placebo or standard plasma infusions) [RR = 0.92, 95% CI (0.85, 0.99)] based on reported outcomes from RCTs carried out in Europe. Finally, convalescent plasma treatment was not associated with improved survival or clinical outcomes in the 14-day subgroup analyses. Conclusions: Outpatients with COVID-19 treated with convalescent plasma had a statistically significantly lower risk of requiring hospital care when compared to those treated with placebo or the standard of care. However, convalescent plasma treatment was not statistically associated with prolonged survival or improved clinical outcomes when compared to placebo or the standard of care, per overall analysis in hospitalized populations. This hints at potential benefits, when used early, to prevent progression to severe disease. Finally, convalescent plasma was significantly associated with better ICU-related outcomes in trials carried out in Europe. Well-designed prospective studies could clarify its potential benefit for specific subpopulations in the post-pandemic era.

Burden of Childhood Malnutrition: A Roadmap of Global and European Policies Promoting Healthy Nutrition for Infants and Young Children.

Childhood malnutrition is a global epidemic with significant public health ramifications. The alarming increase in childhood obesity rates, in conjunction with the COVID-19 pandemic, pose major challenges. The present review aims to critically discuss policies and action plans promoting healthy nutrition among infants and children, globally. Since the Convention on the Rights of the Child in 1989 and the joint consortium held by the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) that led to the "Ten Steps to Successful Breastfeeding", several policymakers and scientific societies have produced relevant reports. Today, the WHO and UNICEF remain the key players on the field, elaborating the guidelines shaped by international expert teams over time, but we still have a long way to go before assuring the health of our children.

The impact of COVID-19 during pregnancy on maternal and neonatal outcomes: a systematic review.

Several months after the onset of the epidemic, COVID-19 remains a global health issue. Scientific data on pregnancy, perinatal outcomes and vertical transmission of SARS-CoV-2 are constantly emerging but are still limited and unclear. The purpose of this systematic review was to summarize current evidence on vertical transmission rates, maternal, perinatal and neonatal outcomes and mode of delivery in pregnancies affected by COVID-19. An extensive search was conducted in PubMed, Google Scholar, Embase, and Scopus databases up to June 20, 2020. A total of 133 articles (51 case reports, 31 case series, 40 cohort studies and 2 case-control studies) reporting data from 8,092 subjects (6,046 pregnant women and 2,046 neonates) were considered eligible for inclusion in the systematic review. A substantial proportion of pregnant women with COVID-19 underwent caesarean section (case reports 82.2%, case series 74.2% and cohort studies 66.0%). Regarding vertical transmission, most neonates were tested negative (case reports 92.7%, case series studies 84.2%, cohort studies 97.1% and case control studies 100%). Maternal mortality rates ranged from 1% in cohort studies to 5.7% in case reports; neonatal mortality ranged from 2% in case reports to 3.3% in case series. Vertical transmission of SARS-CoV-2 from mother to child is rare. Careful screening of pregnant women seems important and specific guidelines with evidence-based decision algorithms for the mode of delivery in the context of a pregnancy affected by COVID-19 should be established.

COVID-19 features in children and adolescents: a systematic review and pooled analysis.

The purpose of the present study was to evaluate special features and probable correlations between symptoms, laboratory findings, treatment, and outcomes of COVID-19 in children and adolescents, through a systematic review and pooled analysis. Following database (Pubmed, Google Scholar, Scopus and Embase) search, forty articles were considered eligible identifying a total of 2,971 confirmed pediatric COVID-19 patients. Fever was reported in 55.1% of the cases, while 28.4% were asymptomatic. Radiological signs of pneumonia were observed in more than half of the cases and in 40.7% of asymptomatic patients. Fever showed the highest sensitivity (sensitivity: 60.3%, specificity: 48.8%), followed by cough (sensitivity: 47.4%, specificity: 76.7%), rhinorrhea (sensitivity: 21.1%, specificity: 88.4%) and diarrhea (sensitivity: 10.3%, specificity: 88.4%), in differentiating cases with positive radiological signs for pneumonia. Compared to school age children, preschoolers (adjusted OR=6.01, 95%CI: 1.73-20.91) were more prone to pneumonia findings. Various combinations of treatments were used across studies, without following any strict guidelines. Most children (>90%) had full recovery and rarely presented complications. Fever seems to be the most frequent symptom in pediatric COVID-19, but pediatricians should additionally evaluate cough, rhinorrhea, and diarrhea as indicators of SARS-CoV-2 infection. Asymptomatic cases were common, but not the majority, and a significant percentage had developed radiologic findings of pneumonia. Thorough reassessment of treatment and management guidelines should be helpful.

Psycho-emotional consequences in pregnant women during the COVID-19 pandemic.

Fear of COVID-19, especially in vulnerable groups such as pregnant women, created excessive concern leading to unexpected psycho-emotional consequences and a need to summarize the most recent knowledge about this topic. Therefore, we conducted a narrative review of the relevant literature, synthesizing data from available databases.

Persisting Endothelial Cell Activation and Hypercoagulability after COVID-19 Recovery—The Prospective Observational ROADMAP-Post COVID-19 Study

Background. Hypercoagulable state and endothelial cell activation are common alterations in patients with COVID-19. Nevertheless, the hypothesis of persistent hypercoagulability and endothelial cell activation following recovery from COVID-19 remains an unresolved issue. Objectives. To investigate the persistence of endothelial cell activation and hypercoagulability after recovery from COVID-19. Patients/Methods. COVID-19 survivors (n = 208) and 30 healthy individuals were enrolled in this study. The following biomarkers were measured: procoagulant phospholipid-dependent clotting time (PPL-ct), D-Dimer, fibrin monomers (FM), free Tissue factor pathway inhibitor (free-TFP)I, heparinase, and soluble thrombomodulin (sTM). Antibodies against SARS-CoV-2 (IgG and IgA) were also measured. Results. The median interval between symptom onset and screening for SARS-CoV-2 antibodies was 62 days (IQR = 22 days). Survivors showed significantly higher levels of D-Dimers, FM, TFPI, and heparanase as compared to that of the control group. Survivors had significantly shorter PPL-ct. Elevated D-dimer was associated with older age. Elevated FM was associated with female gender. Elevated heparanase was independently associated with male gender. Decreased Procoag-PPL clotting time was associated with female gender. One out of four of COVID-19 survivors showed increase at least one biomarker of endothelial cell activation or hypercoagulability. Conclusions. Two months after onset of COVID-19, a significant activation of endothelial cells and in vivo thrombin generation persists in at least one out of four survivors of COVID-19. The clinical relevance of these biomarkers in the diagnosis and follow-up of patients with long COVID-19 merits to be evaluated in a prospective clinical study.

School Performance among Children and Adolescents during COVID-19 Pandemic: A Systematic Review.

As a result of COVID-19 restrictions, conventional ways of schooling were not possible, and in order to continue the educational process new digital resources, such as online learning platforms, were imposed. Although virtual courses provided high-quality educational material, the efficiency in children's and adolescents' academic performance in general is yet to be known. The purpose of this systematic review is to examine whether the academic performance of school-aged students was impacted or not through online learning and modified educational methods during the ongoing COVID-19 pandemic. According to the studies, either students suffered from learning losses comparing to pre-pandemic years or, in some cases, they benefited from online learning, especially in mathematics. Younger students and students with neurodevelopmental disorders or special education needs seemed to suffer more. Parents/caregivers reported that their children's performance deteriorated, while others thought that online learning was beneficial. Teachers also reported that students presented academic gaps and difficulties in mathematics and reading compared to typical years. Consequently, the new ways of schooling imposed by the restrictions have not been fully tested and the impact cannot be described thoroughly. The investment in technological equipment in schools for the majority of students, along with the training of teachers in digital competence, should be a priority.

Play Behaviors in Children during the COVID-19 Pandemic: A Review of the Literature.

Play is a key factor for children's healthy psychological, emotional, social, and cognitive development. During the COVID-19 pandemic, it has been postulated that children's play was affected, not only regarding the time children spent playing but also in terms of the qualitative characteristics of play. The aim of this review was to investigate how children's play has changed during the COVID-19 pandemic. A review was conducted in the PubMed, Google Scholar, EMBASE, SCOPUS, ERIC, PsycInfo, and JSTOR databases up to 6 December 2020. Furthermore, references of eligible studies as well as of relevant articles were searched using a snowballing technique. The search retrieved 17 eligible studies, conducted in Europe and North America. In general, outdoor play was reduced during the pandemic; on the other hand, there was an increase in indoor play and in videogames-screen time. COVID-19 was present in children's pretend play. Children's play was a key contributor to children's mood and wellbeing. Furthermore, teachers were especially concerned about how children's play was affected during the lockdown measures. There is evidence that children's play habits were affected during the COVID-19 pandemic; further research is required, especially cross-culturally oriented.

SARS-CoV-2 antibody kinetics eight months from COVID-19 onset: Persistence of spike antibodies but loss of neutralizing antibodies in 24% of convalescent plasma donors.

Elucidating the characteristics of human immune response against SARS-CoV-2 is of high priority and relevant for determining vaccine strategies. We report the results of a follow-up evaluation of anti-SARS-CoV-2 antibodies in 148 convalescent plasma donors who participated in a phase 2 study at a median of 8.3 months (range 6.8-10.5 months) post first symptom onset. Monitoring responses over time, we found contraction of antibody responses for all four antigens tested, with Spike antibodies showing higher persistence than Nucleocapsid antibodies. A piecewise linear random-effects multivariate regression analysis showed a bi-phasic antibody decay with a more pronounced decrease during the first 6 months post symptoms onset by analysis of two intervals. Interestingly, antibodies to Spike showed better longevity whereas their neutralization ability contracted faster. As a result, neutralizing antibodies were detected in only 76% of patients at the last time point. In a multivariate analysis, older age and hospitalization were independently associated with higher Spike, Spike-RBD, Nucleocapsid, N-RBD antibodies and neutralizing antibody levels. Results on persistence and neutralizing ability of anti-SARS-CoV-2 antibodies, especially against Spike and Spike-RBD, should be considered in the design of future vaccination strategies.

Sexual Activity in Adolescents and Young Adults through COVID-19 Pandemic.

During the COVID-19 pandemic, it has been postulated that the sexual life of adolescent and young adults has been impacted in various aspects, potentially affecting their well-being. Our aim is to investigate the potential changes in the sexual activity and relationships of adolescents and young adults during the COVID-19 pandemic. In general, a decrease in sexual desire was reported during the COVID-19 pandemic, in both genders. Fewer sexual intercourses and bonding behaviors between partners were associated with loneliness and depressive symptoms. On the contrary, an increase in sexual desire was expressed in a few people, with masturbation to be the most preferable means of satisfaction. The present paper highlights the multifaceted impact of COVID-19 upon the sexual life of adolescents and young adults during the ongoing pandemic. The changes observed in their sexual activity and relationships, could provide the basis of future preventive and educational programs.

Obesity in Children and Adolescents during COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has led to special circumstances and changes to everyday life due to the worldwide measures that were imposed such as lockdowns. This review aims to evaluate obesity in children, adolescents and young adults during the COVID-19 pandemic. METHODS: A literature search was conducted to evaluate pertinent studies up to 10 November 2020. RESULTS: A total of 15 articles were eligible; 9 identified 17,028,111 children, adolescents and young adults from 5-25 years old, 5 pertained to studies with an age admixture (n = 20,521) and one study included parents with children 5-18 years old (n = 584). During the COVID-19 era, children, adolescents and young adults gained weight. Changes in dietary behaviors, increased food intake and unhealthy food choices including potatoes, meat and sugary drinks were noted during the ongoing COVID-19 pandemic. Food insecurity associated with financial reasons represents another concern. Moreover, as the restrictions imposed reduced movements out of the house, physical activity was limited, representing another risk factor for weight gain. CONCLUSIONS: COVID-19 restrictions disrupted the everyday routine of children, adolescents and young adults and elicited changes in their eating behaviors and physical activity. To protect them, health care providers should highlight the risk of obesity and provide prevention strategies, ensuring also parental participation. Worldwide policies, guidelines and precautionary measures should ideally be established.

Anti-SARS-CoV-2 Antibody Responses in Convalescent Plasma Donors Are Increased in Hospitalized Patients; Subanalyses of a Phase 2 Clinical Study.

We evaluated the antibody responses in 259 potential convalescent plasma donors for Covid-19 patients. Different assays were used: a commercial ELISA detecting antibodies against the recombinant spike protein (S1); a multiplex assay detecting total and specific antibody isotypes against three SARS-CoV-2 antigens (S1, basic nucleocapsid (N) protein and receptor-binding domain (RBD)); and an in-house ELISA detecting antibodies to complete spike, RBD and N in 60 of these donors. Neutralizing antibodies (NAb) were also evaluated in these 60 donors. Analyzed samples were collected at a median time of 62 (14-104) days from the day of first symptoms or positive PCR (for asymptomatic patients). Anti-SARS-CoV-2 antibodies were detected in 88% and 87.8% of donors using the ELISA and the multiplex assay, respectively. The multivariate analysis showed that age ≥50 years (p < 0.001) and need for hospitalization (p < 0.001) correlated with higher antibody titers, while asymptomatic status (p < 0.001) and testing >60 days after symptom onset (p = 0.001) correlated with lower titers. Interestingly, pseudotype virus-neutralizing antibodies (PsNAbs) significantly correlated with spike and with RBD antibodies by ELISA. Sera with high PsNAb also showed a strong ability to neutralize active SARS-CoV-2 virus, with hospitalized patients showing higher titers. Therefore, convalescent plasma donors can be selected based on the presence of high RBD antibody titers.

The Emerging Role of Convalescent Plasma in the Treatment of COVID-19.

Various agents are currently under evaluation as potential treatments in the fight against coronavirus disease 2019 (COVID-19). Plasma from patients that have overcome COVID-19 infection, referred to as convalescent plasma, is a treatment option with considerable background in viral diseases such as Spanish influenza, H1N1, Ebola, Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS). Although convalescent plasma has historically proven beneficial in the treatment of some viral diseases, its use is still explorative in the context of COVID-19. To date, preliminary evidence from case series is favorable as significant clinical, biochemical improvement and hospital discharge have been reported. A detailed overview of randomized as well non-randomized trials of treatment with convalescent plasma, which have been registered worldwide, is provided in this review. Based on these studies, data from thousands of patients is anticipated in the near future. Convalescent plasma seems to be a safe option, but potential risks such as transfusion-related acute lung injury and antibody-dependent enhancement are discussed. Authorities including the Food and Drug Administration (FDA), and scientific associations such as the International Society of Blood Transfusion (ISBT) and the European Blood Alliance (EBA), have provided guidance into the selection criteria for donors and recipients. A debatable, pivotal issue pertains to the optimal timing of convalescent plasma transfusion. This treatment should be administered as early as possible to maximize efficacy, but at the same time be reserved for severe cases. Emerging risk stratification algorithms integrating clinical and biochemical markers to trace the cases at risk of significant deterioration can prove valuable in this direction.

Derivation and Validation of a Predictive Score for Disease Worsening in Patients with COVID-19.

The prospective observational cohort study COMPASS-COVID-19 aimed to develop a risk assessment model for early identification of hospitalized COVID-19 patients at risk for worsening disease. Patients with confirmed COVID-19 (n = 430) hospitalized between March 18 and April 21, 2020 were divided in derivation (n = 310) and validation (n = 120) cohorts. Two groups became evident: (1) good prognosis group (G-group) with patients hospitalized at the conventional COVID-19 ward and (2) Worsening disease group (W-group) with patients admitted to the intensive care unit (ICU) from the emergency departments. The study end point was disease worsening (acute respiratory failure, shock, myocardial dysfunction, bacterial or viral coinfections, and acute kidney injury) requiring ICU admission. All patients were routinely evaluated for full blood count, prothrombin time, fibrinogen, D-dimers, antithrombin (AT), and protein C activity. Data from the first hospitalization day at the conventional ward or the ICU were analyzed. Cardiovascular risk factors and comorbidities were routinely registered. Obesity, hypertension, diabetes and male gender, increased fibrinogen and D-dimers, thrombocytopenia, AT deficiency, lymphopenia, and an International Society on Thrombosis and Haemostasis (ISTH) score for compensated disseminated intravascular coagulation score (cDIC-ISTH) ≥5 were significant risk factors for worsening disease. The COMPASS-COVID-19 score was derived from multivariate analyses and includes obesity, gender, hemoglobin, lymphocyte, and the cDIC-ISTH score (including platelet count, prothrombin time, D-dimers, AT, and protein C levels). The score has a very good discriminating capacity to stratify patients at high and low risk for worsening disease, with an area under the receiver operating characteristic curve value of 0.77, a sensitivity of 81%, and a specificity of 60%. Application of the COMPASS-COVID-19 score at the validation cohort showed 96% sensitivity. The COMPASS-COVID-19 score is an accurate clinical decision-making tool for an easy identification of COVID-19 patients being at high risk for disease worsening.

Hematological findings and complications of COVID-19.

COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL-6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID-19 patients. Elevated D-Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life-threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID-19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.