Initial impacts of global risk mitigation measures taken during the combatting of the COVID-19 pandemic.

This paper presents an analysis of risk mitigation measures taken by countries around the world facing the current COVID-19 outbreak. In light of the current pandemic the authors collated and clustered (using harmonised terminology) the risk mitigation measures taken around the globe in the combat to contain, and since March 11, 2020, to limit the spread of the SARS-CoV-2 virus known to cause the Coronavirus disease 2019 (COVID-19). This overview gathers lessons learnt, providing an update on the current knowledge for authorities, sectors and first responders on the effectiveness of said measures, and may allow enhanced prevention, preparedness and response for future outbreaks. Various measures such as mobility restrictions, physical distancing, hygienic measures, socio-economic restrictions, communication and international support mechanisms have been clustered and are reviewed in terms of the nature of the actions taken and their qualitative early-perceived impact. At the time of writing, it is still too premature to express the quantitative effectiveness of each risk mitigation cluster, but it seems that the best mitigation results are reported when applying a combination of voluntary and enforceable measures.

The pathology of lethal exposure to the Riot Control Agents: towards a forensics-based methodology for determining misuse.

The aim of this is to review deaths associated with the use of Riot Control Agents (RCAs) and to assess how the presenting pathologies is such cases may better inform cause of death conclusions upon autopsy. We also sought to present which additional steps should be added to the Minnesota protocol and the European harmonization of medico-legal autopsy rules in suspected cases of deaths associated with the use of RCAs. We included 10 lethal cases in our study. In three cases, RCAs were found to be the sole cause of death, in three cases RCAs were ruled a secondary cause of death due asphyxia or asthma subsequent to exposure to RCAs and in four cases RCAs were contributory factors to death. In three cases the responsible agents were identified as Chloroacetophenone (CN), Chlorobenzylidene malononitrile (CS) and Oleoresin capsicum (OC) and in the remaining 7 cases, the agent was OC alone. As there are no specific findings in suspected cases of death associated with RCA use, establishing cause of death and whether RCAs are the sole cause or only a contributory factor will be based on the elimination of other possible causes of death. For this reason, a specifically structured autopsy is essential. This specifically structured autopsy should contain basic principles of the Minnesota Protocol and the European harmonization of medico-legal autopsy rules with the following additional steps taken: examination of clothing, eyes, and skin; examination of pharyngeal, tracheobronchial, and eusophegeal mucosas; and a thorough recording of the steps taken by the party conducting the arrest, including other possible causes of in-custody death, as well as a detailed medical history of the deceased.

Charged amino acid patterns of coreceptor use in the major subtypes of human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 has several genetic subtypes and two coreceptor use phenotypes: R5 that uses CCR5, while X4 uses CXCR4. A high amino acid charge of the envelope glycoprotein 120 V3 region, common at positions 11 and 25, is important for CXCR4 use. We characterized charged V3 amino acids, retrieving all biologically phenotyped sequences from the HIV Sequence Database. Selecting individually unique ones randomly yielded 48 subtype A, 231 B, 180 C, 37 D and 32 CRF01_AE sequences; 482 were R5 and 46 were X4. Charged amino acids were conserved in both R5 and X4 with general and subtype-specific patterns. X4 viruses gained a higher charge from positive amino acids at positions other than in R5, and through the loss of negative amino acids. Other positions than 11/25 had a greater impact on charge (P<0.001). This describes how R5 evolves into X4 in a subtype-specific context, useful for computer-based predictions and vaccine design.

CCR5 use by human immunodeficiency virus type 1 is associated closely with the gp120 V3 loop N-linked glycosylation site.

Human immunodeficiency virus type 1 (HIV-1) enters cells through the chemokine receptors CCR5 (R5 virus) and/or CXCR4 (X4 virus). Loss of N-linked glycans and increased net charge of the third variable loop (V3) of the gp120 envelope glycoprotein have been observed to be important steps towards CXCR4 use. All reported sequences using CCR5 or CXCR4 exclusively, or using both, were gathered from the Los Alamos HIV Database and analysed with regard to the V3 N-linked glycosylation motifs (sequons) and charge. The V3 loop glycan had a sensitivity of 0.98 and a 0.92 positive predictive value in the context of CCR5 use. The difference from X4 was remarkable (P<10(-12)). Especially, the sequon motif NNT within the V3 loop was conserved in 99.2 % of the major clades. The results suggest a close association between the V3 loop glycan and CCR5 use and may provide new insight into HIV-1 tropism and help to improve phenotype-prediction models.

Link between the X4 phenotype in human immunodeficiency virus type 1-infected mothers and their children, despite the early presence of R5 in the child.

Coreceptor use was determined for human immunodeficiency virus type 1 (HIV-1) isolates of various subtypes from 11 women during pregnancy and their infected children. Isolates from peripheral blood mononuclear cells (n=79) and from plasma (n=59) were available. The clinical and immunological stages of HIV-1 infection were recorded. Coreceptor use was tested on human cell lines expressing CD4 and different chemokine receptors. The R5 virus predominated, and only 9 isolates from 2 mothers used CXC chemokine receptor 4. All children carried the R5 virus at the time of diagnosis of HIV-1 infection. In 2 children of mothers carrying the X4 virus, the virus switched from R5 to X4 or to R5X4 by age 18 months (child no. 9) and age 48 months (child no. 10), whereas no children followed up to a similar age whose mothers were carrying the R5 virus experienced such a switch (P=.048). This points to a link between the presence of X4 virus in the mother and the emergence of X4 virus in her child.