Ethical Aspects of COVID-19 Antibody Testing

One common COVID-19 test is the test for one or more of the antibodies the body creates when it encounters the COVID-19 virus. Because these tests are often Point-of-Care, rapid tests that require only a blood sample they may appear to patients as an easily accessible and useful tool for guiding their actions in the pandemic. However, serologic antibody tests should not be offered to patients in normal practice under nearly all circumstances. They are useful in narrow diagnostic settings in later stage infections and they serve an important public health function, but they are not of benefit to patients and may in fact give false and potentially harmful information to patients of moderate health literacy

The Population Affected by the Syndemic of COVID-19 and Poverty is More Likely to be Hospitalized with SARS-CoV-2 Pneumonia

Background Lockdown measures to control COVID-19 have exacerbated the poverty epidemic. We hypothesized that the synergistic interaction of COVID-19 and poverty epidemics favors the development of more severe forms of COVID-19 in the population living in poverty. To test this hypothesis, we assessed whether an ecological association exists between the geographic distribution of hospitalized patients with SARS-CoV-2 pneumonia and markers of poverty in the city of Louisville, KY. Methods Using the geomasked home addresses of hospitalized patients with SARS-CoV-2 pneumonia in the city of Louisville, a kernel density heatmap was created. Kuldorff’s spatial scan statistic was used to calculate areas of increased risk for SARS-CoV-2 pneumonia hospitalization. Heat maps were created for census tract–level demographics according to income, age, race, and ethnicity to assess whether an ecological association exists with the spatial distribution of SARS-CoV-2 pneumonia hospitalization. Results Four areas of increased risk of hospitalization due to SARS-CoV-2 pneumonia were identified in the western and central sections of the city, with relative risks (RRs) ranging from 2.3 to 3.2 (p Conclusions Residents from low-income areas are almost three times more likely to develop SARS-CoV-2 pneumonia requiring hospitalization. Current efforts to decrease the number of COVID-19 hospitalizations through vaccination of populations at risk should be concentrated in city areas with a low-income level population

Genome sequence analysis of La Crosse virus and in vitro and in vivo phenotypes

<p>Abstract</p> <p>Background</p> <p>La Crosse virus (LACV), family <it>Bunyaviridae</it>, is a mosquito-borne virus recognized as a major cause of pediatric encephalitis in North America with 70–130 symptomatic cases each year. The virus was first identified as a human pathogen in 1960 after its isolation from a 4 year-old girl who suffered encephalitis and died in La Crosse, Wisconsin. The majority of LACV infections are mild and never reported, however, serologic studies estimate infection rates of 10–30/100,000 in endemic areas.</p> <p>Results</p> <p>In the present study, sequence analysis of the complete LACV genomes of low-passage LACV/human/1960, LACV/mosquito/1978, and LACV/human/1978 strains and of biologically cloned derivatives of each strain, indicates that circulating LACVs are genetically stable over time and geographic distance with 99.6–100%, 98.9–100%, 97.8–99.6%, and 99.2–99.7% amino acid identity for N, NsS, M polyprotein, and L proteins respectively. We identified 5 amino acid differences in the RNA polymerase and 4 nucleotide differences in the non-coding region of the L segment specific to the human virus isolates, which may result in altered disease outcomes.</p> <p>Conclusion</p> <p>All three wild type viruses had similar <it>in vitro </it>growth kinetics and phenotypes in mosquito C6/36 and Vero cells, and similar levels of neurovirulence and neuroinvasiveness in Swiss Webster mice. The biologically cloned derivative of LACV/human/1960 was significantly less neuroinvasive than its uncloned parent and differed in sequence at one amino acid position in the G_Nglycoprotein, identifying this residue as an attenuating mutation.</p

Superior infectivity for mosquito vectors contributes to competitive displacement among strains of dengue virus

<p>Abstract</p> <p>Background</p> <p>Competitive displacement of a weakly virulent pathogen strain by a more virulent strain is one route to disease emergence. However the mechanisms by which pathogens compete for access to hosts are poorly understood. Among vector-borne pathogens, variation in the ability to infect vectors may effect displacement. The current study focused on competitive displacement in dengue virus serotype 3 (DENV3), a mosquito-borne pathogen of humans. In Sri Lanka in the 1980's, a native DENV3 strain associated with relatively mild dengue disease was displaced by an invasive DENV3 strain associated with the most severe disease manifestations, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), resulting in an outbreak of DHF/DSS. Here we tested the hypothesis that differences between the invasive and native strain in their infectivity for <it>Aedes aegypti </it>mosquitoes, the primary vector of DENV, contributed to the competitive success of the invasive strain</p> <p>Results</p> <p>To be transmitted by a mosquito, DENV must infect and replicate in the midgut, disseminate into the hemocoel, infect the salivary glands, and be released into the saliva. The ability of the native and invasive DENV3 strains to complete the first three steps of this process in <it>Aedes aegypti </it>mosquitoes was measured <it>in vivo</it>. The invasive strain infected a similar proportion of mosquitoes as the native strain but replicated to significantly higher titers in the midgut and disseminated with significantly greater efficiency than the native strain. In contrast, the native and invasive strain showed no significant difference in replication in cultured mosquito, monkey or human cells.</p> <p>Conclusion</p> <p>The invasive DENV3 strain infects and disseminates in <it>Ae. aegypti </it>more efficiently than the displaced native DENV3 strain, suggesting that the invasive strain is transmitted more efficiently. Replication in cultured cells did not adequately characterize the known phenotypic differences between native and invasive DENV3 strains. Infection dynamics within the vector may have a significant impact on the spread and replacement of dengue virus lineages.</p

Vaccine candidates for dengue virus type 1 (DEN1) generated by replacement of the structural genes of rDEN4 and rDEN4Δ30 with those of DEN1

BACKGROUND: Antigenic chimeric viruses have previously been generated in which the structural genes of recombinant dengue virus type 4 (rDEN4) have been replaced with those derived from DEN2 or DEN3. Two vaccine candidates were identified, rDEN2/4Δ30(ME) and rDEN3/4Δ30(ME), which contain the membrane (M) precursor and envelope (E) genes of DEN2 and DEN3, respectively, and a 30 nucleotide deletion (Δ30) in the 3' untranslated region of the DEN4 backbone. Based on the promising preclinical phenotypes of these viruses and the safety and immunogenicity of rDEN2/4Δ30(ME) in humans, we now describe the generation of a panel of four antigenic chimeric DEN4 viruses using either the capsid (C), M, and E (CME) or ME structural genes of DEN1 Puerto Rico/94 strain. RESULTS: Four antigenic chimeric viruses were generated and found to replicate efficiently in Vero cells: rDEN1/4(CME), rDEN1/4Δ30(CME), rDEN1/4(ME), and rDEN1/4Δ30(ME). With the exception of rDEN1/4(ME), each chimeric virus was significantly attenuated in a SCID-HuH-7 mouse xenograft model with a 25-fold or greater reduction in replication compared to wild type DEN1. In rhesus monkeys, only chimeric viruses with the Δ30 mutation appeared to be attenuated as measured by duration and magnitude of viremia. rDEN1/4Δ30(CME) appeared over-attenuated since it failed to induce detectable neutralizing antibody and did not confer protection from wild type DEN1 challenge. In contrast, rDEN1/4Δ30(ME) induced 66% seroconversion and protection from DEN1 challenge. Presence of the Δ30 mutation conferred a significant restriction in mosquito infectivity upon rDEN1/4Δ30(ME) which was shown to be non-infectious for Aedes aegypti fed an infectious bloodmeal. CONCLUSION: The attenuation phenotype in SCID-HuH-7 mice, rhesus monkeys, and mosquitoes and the protective immunity observed in rhesus monkeys suggest that rDEN1/4Δ30(ME) should be considered for evaluation in a clinical trial