Ethical issues in the use of leftover samples and associated personal data obtained from diagnostic laboratories.

Diagnostic laboratories are an integral part of the research ecosystem in biomedical sciences. Among other roles, laboratories are a source of clinically-characterized samples for research or diagnostic validation studies. Particularly during the COVID-19 pandemic, this process was entered by laboratories with different experience in the ethical management of human samples. The objective of this document is to present the current ethical framework regarding the use of leftover samples in clinical laboratories. Leftover samples are defined as the residue of a sample that has been obtained and used for clinical purposes, and would otherwise be discarded. Secondary use of samples typically demands institutional ethical oversight and informed consent by the participants, although the latter requirement could be exempted when the harm risks are sufficiently small. However, ongoing discussions have proposed that minimal risk is an insufficient argument to allow the use of samples without consent. In this article, we discuss both positions, to finally suggest that laboratories anticipating the secondary use of samples should consider the adoption of broad informed consent, or even the implementation of organized biobanking, in order to achieve higher standards of ethical compliance which would enhance their capacity to fulfill their role in the production of knowledge.

Overview of the SARS-CoV-2 genotypes circulating in Latin America during 2021

Latin America is one of the regions in which the COVID-19 pandemic has a stronger impact, with more than 72 million reported infections and 1.6 million deaths until June 2022. Since this region is ecologically diverse and is affected by enormous social inequalities, efforts to identify genomic patterns of the circulating SARS-CoV-2 genotypes are necessary for the suitable management of the pandemic. To contribute to the genomic surveillance of the SARS-CoV-2 in Latin America, we extended the number of SARS-CoV-2 genomes available from the region by sequencing and analyzing the viral genome from COVID-19 patients from seven countries (Argentina, Brazil, Costa Rica, Colombia, Mexico, Bolivia, and Peru). Subsequently, we analyzed the genomes circulating mainly during 2021 including records from GISAID database from Latin America. A total of 1,534 genome sequences were generated from seven countries, demonstrating the laboratory and bioinformatics capabilities for genomic surveillance of pathogens that have been developed locally. For Latin America, patterns regarding several variants associated with multiple re-introductions, a relatively low percentage of sequenced samples, as well as an increment in the mutation frequency since the beginning of the pandemic, are in line with worldwide data. Besides, some variants of concern (VOC) and variants of interest (VOI) such as Gamma, Mu and Lambda, and at least 83 other lineages have predominated locally with a country-specific enrichments. This work has contributed to the understanding of the dynamics of the pandemic in Latin America as part of the local and international efforts to achieve timely genomic surveillance of SARS-CoV-2.

Overview of the SARS-CoV-2 genotypes circulating in Latin America during 2021.

Latin America is one of the regions in which the COVID-19 pandemic has a stronger impact, with more than 72 million reported infections and 1.6 million deaths until June 2022. Since this region is ecologically diverse and is affected by enormous social inequalities, efforts to identify genomic patterns of the circulating SARS-CoV-2 genotypes are necessary for the suitable management of the pandemic. To contribute to the genomic surveillance of the SARS-CoV-2 in Latin America, we extended the number of SARS-CoV-2 genomes available from the region by sequencing and analyzing the viral genome from COVID-19 patients from seven countries (Argentina, Brazil, Costa Rica, Colombia, Mexico, Bolivia, and Peru). Subsequently, we analyzed the genomes circulating mainly during 2021 including records from GISAID database from Latin America. A total of 1,534 genome sequences were generated from seven countries, demonstrating the laboratory and bioinformatics capabilities for genomic surveillance of pathogens that have been developed locally. For Latin America, patterns regarding several variants associated with multiple re-introductions, a relatively low percentage of sequenced samples, as well as an increment in the mutation frequency since the beginning of the pandemic, are in line with worldwide data. Besides, some variants of concern (VOC) and variants of interest (VOI) such as Gamma, Mu and Lambda, and at least 83 other lineages have predominated locally with a country-specific enrichments. This work has contributed to the understanding of the dynamics of the pandemic in Latin America as part of the local and international efforts to achieve timely genomic surveillance of SARS-CoV-2.

Infants Younger Than 6 Months Infected With SARS-CoV-2 Show the Highest Respiratory Viral Loads.

There is a paucity of reports on the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in infants, because most studies have grouped infants with older children. We analyzed the viral loads of 45318 SARS-CoV-2-positive nasopharyngeal swab samples obtained in Buenos Aires, Argentina. Infants younger than 6 months presented higher viral loads than any other age group. Children older than 6 months showed significantly lower viral loads, similar to those founds in adults. This observation raises new questions regarding the role of infants in the spreading of SARS-CoV-2 infection.

Platelets modulate CD4+ T-cell function in COVID-19 through a PD-L1 dependent mechanism.

Severe COVID-19 is associated with a systemic inflammatory response and progressive CD4+ T-cell lymphopenia and dysfunction. We evaluated whether platelets might contribute to CD4+ T-cell dysfunction in COVID-19. We observed a high frequency of CD4+ T cell-platelet aggregates in COVID-19 inpatients that inversely correlated with lymphocyte counts. Platelets from COVID-19 inpatients but not from healthy donors (HD) inhibited the upregulation of CD25 expression and tumour necrosis factor (TNF)-α production by CD4+ T cells. In addition, interferon (IFN)-γ production was increased by platelets from HD but not from COVID-19 inpatients. A high expression of PD-L1 was found in platelets from COVID-19 patients to be inversely correlated with IFN-γ production by activated CD4+ T cells cocultured with platelets. We also found that a PD-L1-blocking antibody significantly restored platelets' ability to stimulate IFN-γ production by CD4+ T cells. Our study suggests that platelets might contribute to disease progression in COVID-19 not only by promoting thrombotic and inflammatory events, but also by affecting CD4+ T cells functionality.

Detection of SARS-CoV-2 RNA by PCR in a series of corpses sent for autopsy

Following the emergence of SARS-CoV-2 in the world, the COVID-19 pandemic broke out, affecting 185 countries. There have been numerous scientific publications presenting epidemiological, clinical, statistical, and microbiological data. The high mortality has implied the need for increasingly accurate data regarding the virus and its behaviour in the environment and, on the other hand, faced health teams with a serious problem in relation to the safe handling of corpses and the risks of transmission that this implies. The objective of this study was to detect the presence of SARS-CoV-2 RNA in corpses sent to the National Judicial Morgue that were not included in the definition of a suspected case submitted by the Argentine Ministry of Health. Nasopharyngeal and oropharyngeal swabs were taken from 101 cadavers chosen randomly and based on inclusion criteria for detection of viral RNA using the RT-PCR technique. Of the cadavers included in the study, 16.8%, not classified as suspected cases of COVID-19, were tested for the presence of viral RNA in the samples collected. Resumen A partir de la emergencia del SARS-CoV-2 en el mundo se desató la pandemia por COVID-19 que afectó a 185 países;aparecieron numerosas publicaciones científicas presentando datos epidemiológicos, clínicos, estadísticos y microbiológicos. La elevada mortalidad ha implicado la necesidad de contar con datos cada vez más precisos con relación al virus y a su comportamiento en el medio y, por otro lado, enfrentó a los equipos de salud con un grave problema con relación al manejo seguro de cadáveres y a los riesgos de transmisión que ello implica. El objetivo del presente estudio ha sido detectar la presencia de ARN del SARS-CoV-2 en cadáveres remitidos a la Morgue Judicial de la Nación que no estuvieran comprendidos en la definición de caso sospechoso propuesta por el Ministerio de Salud de la Nación de la República Argentina. Se realizaron hisopados nasofaríngeos a 101 cadáveres elegidos aleatoriamente y basándose en criterios de inclusión para la detección de ARN viral mediante técnica RT-PCR. Se detectó ARN viral en el 16,8% de los cadáveres incluidos en el estudio.

AHR signaling is induced by infection with coronaviruses.

Coronavirus infection in humans is usually associated to respiratory tract illnesses, ranging in severity from mild to life-threatening respiratory failure. The aryl hydrocarbon receptor (AHR) was recently identified as a host factor for Zika and dengue viruses; AHR antagonists boost antiviral immunity, decrease viral titers and ameliorate Zika-induced pathology in vivo. Here we report that AHR is activated by infection with different coronaviruses, potentially impacting antiviral immunity and lung epithelial cells. Indeed, the analysis of single-cell RNA-seq from lung tissue detected increased expression of AHR and AHR transcriptional targets, suggesting AHR signaling activation in SARS-CoV-2-infected epithelial cells from COVID-19 patients. Moreover, we detected an association between AHR expression and viral load in SARS-CoV-2 infected patients. Finally, we found that the pharmacological inhibition of AHR suppressed the replication in vitro of one of the causative agents of the common cold, HCoV-229E, and the causative agent of the COVID-19 pandemic, SARS-CoV-2. Taken together, these findings suggest that AHR activation is a common strategy used by coronaviruses to evade antiviral immunity and promote viral replication, which may also contribute to lung pathology. Future studies should further evaluate the potential of AHR as a target for host-directed antiviral therapy.

A DNA intercalating dye-based RT-qPCR alternative to diagnose SARS-CoV-2.

Early detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been proven crucial during the efforts to mitigate the effects of the COVID-19 pandemic. Several diagnostic methods have emerged in the past few months, each with different shortcomings and limitations. The current gold standard, RT-qPCR using fluorescent probes, relies on demanding equipment requirements plus the high costs of the probes and specific reaction mixes. To broaden the possibilities of reagents and thermocyclers that could be allocated towards this task, we have optimized an alternative strategy for RT-qPCR diagnosis. This is based on a widely used DNA-intercalating dye and can be implemented with several different qPCR reagents and instruments. Remarkably, the proposed qPCR method performs similarly to the broadly used TaqMan-based detection, in terms of specificity and sensitivity, thus representing a reliable tool. We think that, through enabling the use of vast range of thermocycler models and laboratory facilities for SARS-CoV-2 diagnosis, the alternative proposed here can increase dramatically the testing capability, especially in countries with limited access to costly technology and reagents.