Prevalence and Clinical Impact of SARS-CoV-2 Silent Carriers Among Actively Treated Patients with Cancer During the COVID-19 Pandemic.

INTRODUCTION: In Europe, the SARS-CoV-2 pandemic had its first epicenter in Italy. Despite a significant mortality rate, the severity of most cases of COVID-19 infection ranges from asymptomatic to mildly symptomatic, and silent infection affects a still-unknown proportion of the general population. No information is available on the prevalence and clinical impact of SARS-CoV-2 silent infection among patients with cancer receiving anticancer treatment during the pandemic. MATERIALS AND METHODS: From April 1, 2020, to the end of the same month, 560 consecutive patients with cancer, asymptomatic for COVID-19 and on anticancer treatment at Papa Giovanni XXIII Hospital in Bergamo, were evaluated and tested for SARS-CoV-2. We implemented a two-step diagnostics, including the rapid serological immunoassay for anti-SARS-CoV-2 immunoglobulin (Ig) G/IgM and the nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) test in case of seropositivity to identify SARS-CoV-2 silent carriers. RESULTS: In 560 patients, 172 (31%) resulted positive for anti-SARS-CoV-2 IgM/IgG antibodies, regardless of different type of cancer, stage, and treatment. The Ig-seropositive patients were then tested with RT-PCR nasopharyngeal swabs, and 38% proved to be SARS-CoV-2 silent carriers. At an early follow-up, in the 97 SARS-CoV-2-seropositive/RT-PCR-negative patients who continued their anticancer therapies, only one developed symptomatic COVID-19 illness. CONCLUSION: Among patients with cancer, the two-step diagnostics is feasible and effective for SARS-CoV-2 silent carriers detection and might support optimal cancer treatment strategies at both the individual and the population level. The early safety profile of the different anticancer therapies, in patients previously exposed to SARS-CoV-2, supports the recommendation to continue the active treatment, at least in cases of RT-PCR-negative patients. IMPLICATIONS FOR PRACTICE: This is the first study evaluating the prevalence and clinical impact of SARS-CoV-2 silent infection in actively treated patients with cancer, during the epidemic peak in one of the worst areas of the COVID-19 pandemic. Lacking national and international recommendations for the detection of asymptomatic SARS-CoV-2 infection, a pragmatic and effective two-step diagnostics was implemented to ascertain SARS-CoV-2 silent carriers. In this series, consisting of consecutive and unselected patients with cancer, the prevalence of both SARS-CoV-2-seropositive patients and silent carriers is substantial (31% and 10%, respectively). The early safety profile of the different anticancer therapies, in patients previously exposed to SARS-CoV-2, supports the recommendation to continue the active treatment, at least in case of RT-PCR-negative patients.

Predicting optimal lockdown period with parametric approach using three-phase maturation SIRD model for COVID-19 pandemic.

This paper proposes a three-phase Susceptible-Infected-Recovered-Dead (3P-SIRD) model to calculate an optimal lockdown period for some specific geographical regions that will be favorable to break not only the transmission chain but also will help country's economy to recover and support infrastructure in a fight against COVID-19. Proposed model is novel since it additionally includes parameters i.e. silent carriers, sociability of newly infected person and unregistered died coronavirus infected people along with the infection rate, suspected rate and death rate. These parameters contribute a lot to figure out the more clear model, along with essential parameters. The model takes the testing rate of suspected people into consideration and this rate varies with respect to phase of the epidemic growth. Proposed 3P-SIRD model is divided into three-phases based on the awareness and sustainability of disease. Time is divided into different periods as rate of infection and recovery fluctuates region to region. The model is tested on China data and is efficient enough to propose a model very close to their actual figures of infected people, recovered people, died and active cases. The model predicts the optimal lockdown period as 73 days for China which is very close to their actual lockdown period (77 days). Further, the model is implemented to predict the optimal lockdown period of India and Italy.

Genotype-Phenotype Correlation of ß-Thalassemia in Malaysian Population: Toward Effective Genetic Counseling.

Effective prevention of ß-thalassemia (ß-thal) requires strategies to detect at-risk couples. This is the first study attempting to assess the prevalence of silent ß-thal carriers in the Malaysian population. Hematological and clinical parameters were evaluated in healthy blood donors and patients with ß-thal trait, Hb E (HBB: c.79G>A)/ß-thal and ß-thal major (ß-TM). ß-Globin gene sequencing was carried out for 52 healthy blood donors, 48 patients with Hb E/ß-thal, 34 patients with ß-TM and 38 patients with ß-thal trait. The prevalence of silent ß-thal carrier phenotypes found in 25.0% of healthy Malaysian blood donors indicates the need for clinician's awareness of this type in evaluating ß-thal in Malaysia. Patients with ß-TM present at a significantly younger age at initial diagnosis and require more blood transfusions compared to those with Hb E/ß-thal. The time at which genomic DNA was extracted after blood collection, particularly from patients with ß-TM and Hb E/ß-thal, was found to be an important determinant of the quality of the results of the ß-globin sequencing. Public education and communication campaigns are recommended as apparently healthy individuals have few or no symptoms and normal or borderline hematological parameters. ß-Globin gene mutation characterization and screening for silent ß-thal carriers in regions prevalent with ß-thal are recommended to develop more effective genetic counseling and management of ß-thal.

A Novel Variant in AKAP9 Gene, a Controversial Gene, in Long QT Syndrome.

Introduction: Long QT syndrome (LQTS) is a common congenital cause of fatal cardiac arrhythmia. Characteristic clinical findings are prolonged QT interval and ventricular arrhythmia on electrocardiogram (ECG), syncope, seizure, and sudden death. It is a genetically heterogeneous disease. To date, disease-causing variant have been reported in seventeen genes. The AKAP9 is still considered controversial among those genes. Case Report: We report the case of a 10-year-old female who was born from a non-consanguineous Turkish couple. She visited pediatrics cardiology clinic presenting with dyspnea and tachycardia. Prolongation of the QT interval was detected in her ECG. Panel test associated with LQTS genes was performed. She was diagnosed with long QTS type 11 due to a heterozygous variant in AKAP9:c.11487_11489 delTACinsCGTA, p.(Thr3830ValfsTer12), that was revealed through next-generation sequencing test. The variant was also found in her mother and brother. Discussion and Conclusion: Novel heterozygous frameshift variant in the AKAP9 gene was considered as "Uncertain Significance (VUS)" in the ACMG classification. The novel variant is absent from population databases (PM2); it is a null variant (PVS1_moderate). AKAP9 gene has the lowest known rate among the causes of LQTS. Information is limited on genotype-phenotype correlation. Yet it is still among the candidate genes. Although the relationship of the AKAP9 gene with LQTS has not yet been fully indicated, individuals with a pathogenic variant in AKAP9 gene and silent carriers may be at risk for fatal cardiac events. Improvements of the genetic tests in the near future may contribute to the literature and clinical research about AKAP9 gene.