The Positive Rate of Nucleic Acid Testing and the Epidemiological Characteristics of COVID-19 in Chongqing

ObjectiveThe purpose of this study is to analyze the positive rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid testing (NAT), cases of and deaths due to SARS-CoV-2, and the epidemiological characteristics of SARS-CoV-2 to identify high-risk populations.MethodsA retrospective study in Jiulongpo district of Chongqing was conducted by performing continuous observations of the frequency of SARS-CoV-2 NAT, analyzing the data of close contacts of patients and asymptomatic carriers, and collecting epidemiological data. Data were collected from January 20, 2020, when the first case of SARS-CoV-2 infection was reported, to March 26, 2020. Descriptive statistical analysis and Cochrane–Mantel–Haenszel analysis were used to compare the positive detection rates and positive diagnostic rates of different exposure groups.ResultsA total of 7,118 people received 10,377 SARS-CoV-2 nucleic acid tests in one district, and the SARS-CoV-2 positive rates were 0.40% (18/4446) and 0.15% (4/2672) in people receiving one and ≥ two nucleic acid tests (p = 0.06), respectively. Those with suspected cases (12.35%) and close contacts (8%) had higher positive rates than people tested at fever clinics (0.39%) (p < 0.001). The median latency (range) of cases was 5 (2, 9) days, and the median time from diagnosis to recovery was 22 (14, 25) days. One recovered patient received a positive test result at 28 days after recovery when she attempted to donate blood. Six clustered cases, including one patient who died, indicated persistent human-to-human transmission. One patient who was diagnosed after death was found to have infected 13 close contacts. People working in catering and other public service departments (36.36%) and people who are unemployed and retirees (45.45%) have an increased risk of infection compared with technical staff (9.09%) and farmers (9.09%).ConclusionThe total positive rate was low in the tested population, and more effective detection ranges should be defined to improve precise and differentiated epidemic control strategies. Moreover, in asymptomatic carriers, SARS-CoV-2 tests were positive after recovery, and patients with suspected SARS-CoV-2 infection who die may pose serious potential transmission threats.

Infection by SARS CoV-2 in healthcare workers of a second level hospital

Background: From the first Covid-19 case in Playa del Carmen, 370 cases of infection have been reported in our staff until December 31, 2020. Material and Methods: Study in workers of the General Hospital who developed SARCOV-2 infection during the pandemic. A sample of 30 cases of both sexes with laboratory-confirmed infection was obtained. Descriptive statistics were used with measures of central tendency, dispersion and percentages. Results: In a sample of 30 workers there were 13 doctors, 6 nurses and 11 support workers. The age was obtained as a mean of 38.8 years and SD = 10.4. Only four risk factors were found. Of the 30 infected health workers, 27 were treated on an outpatient basis and three required hospitalization. Discussion: The main symptoms in health workers are alterations in the sensation of taste and smell, but unlike our study, was headache, fever and myalgia. Likewise, it has been observed that medical are the most affected, but in this study, it was support and the least affected was nursing personnel. There is no doubt that asymptomatic carriers are a serious disease transmission problem such that transmission between health workers by asymptomatic carriers is possible as was observed in this analysis. Keywords: COVID-19; SARS-CoV-2; Healthcare Workers; Nosocomial Transmission; Asymptomatic Carriers; Diagnostic Testing

Asymptomatic carriers of the p.A53T SNCA mutation: data from the PPMI study

IntroductionThere has been great interest in the prodromal phase of Parkinson’s disease (PD), especially in subjects who are asymptomatic carriers of genetic mutations leading to PD because of the high risk to convert to PD. The objective of the present study was to assess non motor characteristics of asymptomatic p.A53T mutation carriers (A53T-AC) compared with healthy controls (HC).MethodsWe compared 12 A53T-AC with 36 matched HC enrolled into in the Parkinson’s Progression Markers Initiative (PPMI) study. Baseline data extracted from the PPMI database, contained demographics and non-motor symptoms (e.g. the Montreal Cognitive Assessment (MOCA) for cognition, the University of Pennsylvania Smell Identification Test (UPSIT) for olfaction, MDS-UPDRS I etc.)ResultsThe mean UPSIT score was lower in A53T-AC vs HC (p =0.000). MoCA test showed a trend towards lower scores in A53T AC. We found a significant positive correlation between UPSIT score and MOCA in A53T-AC (rs = 0,68, p=0,021) but not in HC. Total scores for MDS-UPDRS I did not differ between the groups but the subscore of anxiety was more prevalent in A53T-AC.ConclusionThe more affected olfaction in A53T-AC may indicate that olfactory function is affected quite early in A53T carriers. The strong positive correlation between UPSIT and MOCA in the A53T-AC group may indicate that cognitive dysfunction and olfactory impairment progress alongside, prior to nigrostriatal degeneration. Anxiety was also more prevalent in A53T-AC and may represent an additional prodromal feature in this group of subjects.

Phylogenomics and population genomics of SARS-CoV-2 in Mexico during the pre-vaccination stage reveals variants of interest B.1.1.28.4 and B.1.1.222 or B.1.1.519 and the nucleocapsid mutation S194L associated with symptoms

Understanding the evolution of the SARS-CoV-2 virus in various regions of the world during the Covid-19 pandemic is essential to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. A real-time quantitative PCR screening and phylogenomic reconstructions directed at sequence/structure analysis of the spike glycoprotein revealed mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show spike protein mutations in the N-terminal domain (i.e. R190M), in the receptor-binding motif (i.e. T478K, E484K), within the S1–S2 subdomains (i.e. P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the variants of interest we postulate: 20B/478K.V1 (B.1.1.222 or B.1.1.519) and 20B/P.4 (B.1.1.28.4). Moreover, the population patterns of single nucleotide variants from symptomatic and asymptomatic carriers obtained with a self-sampling scheme confirmed the presence of several fixed variants, and differences in allelic frequencies among localities. We identified the mutation N:S194L of the nucleocapsid protein associated with symptomatic patients. Phylogenetically, this mutation is frequent in Mexican sub-clades. Our results highlight the dual and complementary role of spike and nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage.

Infection in asymptomatic carriers of SARS-CoV-2 can interfere with the achievement of robust immunity on a population scale

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide as a severe pandemic, and a significant portion of the infected population may remain asymptomatic. Given this, five surveys were carried out between May and September 2020 with a total of 3585 volunteers in the municipality of Foz do Iguaçu, State of Paraná, a triple border region between Brazil/Argentina/Paraguay. Five months after the first infection, volunteers were re-analysed for the production of IgG anti-Spike and anti-RBD-Spike, in addition to analyses of cellular immunity. Seroconversion rates ranged from 4.4 % to a peak of 37.21 % followed by a reduction in seroconversion to 21.1 % in September, indicating that 25 % of the population lost their circulating anti-SARS-CoV-2 antibodies 3 months after infection. Analyses after 5 months of infection showed that only 17.2 % of people still had anti-RBD-Spike antibodies, however, most volunteers had some degree of cellular immune response. The strategy of letting people become naturally infected with SARS-CoV-2 to achieve herd immunity is flawed, and the first contact with the virus may not generate enough immunogenic stimulus to prevent a possible second infection.

Immunoprofiling of fresh HAM/TSP blood samples show altered innate cell responsiveness

The Human T-cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a devastating neurodegenerative disease with no effective treatment, which affects an increasing number of people in Brazil. Immune cell from the adaptive compartment are involved in disease manifestation but whether innate cell functions participate in disease occurrence has not been evaluated. In this study, we analyzed innate cell responses at steady state and after blood cell stimulation using an agonist of the toll-like receptor (TLR)7/8-signaling pathway in blood samples from HTLV-1-infected volunteers, including asymptomatic carriers and HAM/TSP patients. We observed a lower response of IFNα+ DCs and monocytes in HAM/TSP compared to asymptomatic carriers, as a potential consequence of corticosteroid treatments. In contrast, a higher frequency of monocytes producing MIP-1α and pDC producing IL-12 was detected in HAM/TSP blood samples, together with higher IFNγ responsiveness of NK cells, suggesting an increase sensitivity to inflammatory response in HAM/TSP patients compared to asymptomatic carriers. This sustained inflammatory responsiveness could be linked or be at the origin of the neuroinflammatory status in HAM/TSP patients. Therefore, the mechanism underlying this dysregulations could shed light onto the origins of HAM/TSP disease.

Immune Senescence-Related Gene Expression Profile in CD4+ T-Lymphocytes of HTLV-1 Asymptomatic Carriers and Patients with Adult T-Cell Leukemia/Lymphoma (ATLL): A Brazilian Preliminary Study

Introduction: Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive neoplasm caused by the human T-lymphotropic virus type 1 (HTLV-1). It is estimated, worldwide, that at least 5-10 million people carry HTLV-1 and 2-5% out of them will develop ATLL. Previously, our group demonstrated an increase of cells in G0/G1 phase of cell cycle and aneuploidy in CD4+ T-cells in HTLV-1 asymptomatic carriers [1]. These findings may reflect an adverse intracellular environment, caused by genetic stress due to viral particles inserted into host DNA. Intracellular mechanisms aiming to control and prevent replication of cells carrying genetic aberrations in genes involved in cell cycle regulation, DNA repair and apoptosis could be activated to hold cell division while DNA damage is repaired. Based on this hypothesis, delay of cell cycle in G0/G1 may be a step in the process of oncogenesis [1]. Herein, we did a pilot study in order to analyze the pattern of expression of a set of genes involved in cell cycle control and senescence in CD4+ T-lymphocytes of HTLV-1 infected individuals searching for additional genetic abnormalities in this setting. Methods: Peripheral blood samples were tested obtained from five HTLV-1 asymptomatic carriers and four ATLL patients for this pilot study. T-CD4+ cells were isolated in magnetic column followed by RNA extraction. Subsequently, it was converted into cDNA for the assays of the real-time quantitative polymerase chain reaction (qRT-PCR) in microplates of 96 wells previously customized with 44 senescence related genes pursued from ThermoFischer Scientific. A pool of five samples from healthy individuals (control group) was used as a calibrator. RNA transcription was measured using 7500 Fast real time PCR system (Applied Biosystems) and data were collected by the 7500 software v2.0.5 (Applied Biosystems). The expression levels of the target genes were calculated using the Livak and Schmittgen (2001) method [2]. The mRNA expression was normalized using the β-glucuronidase (GUSB) gene (Applied Biosystems, cod. Hs99999908_m1) and those genes with expression ≥ 2x or ≤ 2x in comparison to control group were considered as differentially expressed and were chosen to be validated in a secondary cohort of thirty HTLV-1 infected individuals. Results: In HTLV-1 asymptomatic carriers the median age was 55 years (37-62 years) and 20% (1/5) of them were males, in ATLL patients: 45 years (38-66 years) and 100% (4/4) were females, while the control group had median age of 43 years (22-62 years) and 60% (3/5) were males. Among the ATLL group, 50% (2/4) were classified as smoldering, 25% (1/4) were acute and 25% (1/4) were lymphomatous, according to Shimoyama classification [3]. COL3A1, SPARC and TWIST1 genes were overexpressed and CDKN1A, ID1, IFNG and TERT were suppressed in HTLV-1 asymptomatic carriers when compared to healthy controls. HTLV-1 infected and ATLL patients showed TWIST1 and COL3A1 genes overexpressed and IFNG, CDKN1A and TERT repressed (Figure 1 and 2). The ALDH1, FN1, NOX4 and COL1A1 genes did not amplified. Conclusion: These preliminaries results showed for the first time that HTLV-1 asymptomatic carriers present a set of genes differentially expressed in T-CD4+ cells, especially SPARC, TWIST1, COL3A1, CDNK1A and IFNG. These results will be confirmed in a validation cohort. We expected that this data shed some light on the comprehension of the cell microenvironment of the T-CD4+ lymphocyte in HTLV-1 asymptomatic carriers. Furthermore, we will be able to understand potential mechanisms associated with leukemogenesis in chronic infection by this virus, explaining eventual progression to ATLL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.