COVID-19 in Latin America: Where We Stand and What Is to Come

As infection rates decrease, much of Latin America seems to be taking a breather from the onslaught of COVID-19. However access to vaccines is unequal, both within and between individual countries, while vaccine coverage is heterogeneous. Combined with uneven infection rates and the arrival of the highly contagious Delta variant, new epidemiological and policy challenges must be addressed. With 45 million registered infections and almost one-third of all COVID-19-related deaths worldwide, Latin America has become a global hotspot in the pandemic. While Chile and Costa Rica have higher vaccination rates than Germany or the United States, half of Latin America's population has yet to receive their first jab. What may come to the rescue are the high numbers of people who have acquired some immunity from past COVID-19 infections beyond those identified in official statistics. Vaccine diplomacy has changed colours. Initially, Latin America depended on vaccine shipments from China, India, and Russia. By now, the US and the multilateral COVAX initiative have become the largest providers. Policies will need to adjust to the resulting mix of vaccines of varying efficacy and varying international recognition. To reduce external dependence, the region will need to build up its capacity to develop and mass-produce vaccines, diagnostic equipment, and mRNA technology. The vaccines developed in Cuba could become part of the vaccine portfolio the continent will need for many years to come. The pandemic has exposed the region's structural weaknesses. Public-health funding must be stepped up; ad hoc social-policy measures taken in the pandemic should be harnessed to make social safety nets more resilient and inclusive. A strong vaccination drive remains key to keeping the pandemic at bay. As immunity - whether from past infection or vaccination - will eventually wane, vaccination may need to be integrated into routine preventive healthcare. Cooperation transcending ideological left-right dichotomies in epidemiological diagnosis, research, vaccination, and healthcare provision must become a priority within the region as well as for international partners

Association of hepatitis C virus genotype 2 spread with historic slave trade and commerce routes in Western Africa

The hepatitis C virus genotype 2 (HCV2) is endemic in Western and Central Africa. The HCV2 evolutionary origins remain uncertain due to the paucity of available genomes from African settings. In this study, we investigated the molecular epidemiology of HCV infections in rural Guinea, Western Africa, during 2004 and 2014. Broadly reactive nested reverse transcription polymerase chain reaction (RT-PCR)-based screening of sera from 1,571 asymptomatic adults resulted in the detection of 25 (1.5 per cent; 95 per cent confidence interval 0.9-2.3) positive samples, with a median viral load of 2.54E + 05 IU/ml (interquartile range 6.72E + 05). HCV-infected persons had a median age of 47 years, and 62.5 per cent were male and 37.5 per cent were female. The full polyprotein-encoding genes were retrieved by a combination of high throughput and Sanger sequencing from 17 samples showing sufficiently high viral loads. Phylogenetic analysis and sequence distances >= 13 per cent averaged over the polyprotein genes compared to other HCV2 subtypes revealed nine previously unknown HCV2 subtypes. The time to the most recent common ancestor of the Guinean HCV2 strains inferred in a Bayesian framework was 493 years (95 per cent Highest posterior density (HPD) 453-532). Most of the Guinean strains clustered poorly by location on both the level of sampling sites within Guinea and the level of countries in the phylogenetic reconstructions. Ancestral state reconstruction provided decisive support (Bayes factor > 100) for an origin of HCV2 in Western Africa. Phylogeographic reconstructions in a Bayesian framework pointed to a radial diffusion of HCV2 from Western African regions encompassing today's countries like Ghana, Guinea Bissau, or Burkina Faso, to Central and Northern African regions that took place from the 16th century onwards. The spread of HCV2 coincided in time and space with the main historic slave trade and commerce routes, supported by Bayesian tip-association significance testing (P = 0.01). Our study confirms the evolutionary origins of HCV2 in Western Africa and provides a potential link between historic human movements and HCV2 dispersion

Identification of a contemporary human parechovirus type 1 by VIDISCA and characterisation of its full genome

<p>Abstract</p> <p>Background</p> <p>Enteritis is caused by a spectrum of viruses that is most likely not fully characterised. When testing stool samples by cell culture, virus isolates are sometimes obtained which cannot be typed by current methods. In this study we used VIDISCA, a virus identification method which has not yet been widely applied, on such an untyped virus isolate.</p> <p>Results</p> <p>We found a human parechovirus (HPeV) type 1 (strain designation: BNI-788st). Because genomes of contemporary HPeV1 were not available, we determined its complete genome sequence. We found that the novel strain was likely the result of recombination between structural protein genes of an ancestor of contemporary HPeV1 strains and nonstructural protein genes from an unknown ancestor, most closely related to HPeV3. In contrast to the non-structural protein genes of other HPeV prototype strains, the non-structural protein genes of BNI-788st and HPeV3 prototype strains did not co-segregate in bootscan analysis with that of other prototype strains.</p> <p>Conclusion</p> <p>HPeV3 nonstructural protein genes may form a distinct element in a pool of circulating HPeV non-structural protein genes. More research into the complex HPeV evolution is required to connect virus ecology with disease patterns in humans.</p

Potential zoonotic sources of SARS‐CoV‐2 infections

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing coronavirus disease-2019 (COVID-19) likely has evolutionary origins in other animals than humans based on genetically related viruses existing in rhinolophid bats and pangolins. Similar to other animal coronaviruses, SARS-CoV-2 contains a functional furin cleavage site in its spike protein, which may broaden the SARS-CoV-2 host range and affect pathogenesis. Whether ongoing zoonotic infections are possible in addition to efficient human-to-human transmission remains unclear. In contrast, human-to-animal transmission can occur based on evidence provided from natural and experimental settings. Carnivores, including domestic cats, ferrets and minks, appear to be particularly susceptible to SARS-CoV-2 in contrast to poultry and other animals reared as livestock such as cattle and swine. Epidemiologic evidence supported by genomic sequencing corroborated mink-to-human transmission events in farm settings. Airborne transmission of SARS-CoV-2 between experimentally infected cats additionally substantiates the possibility of cat-to-human transmission. To evaluate the COVID-19 risk represented by domestic and farmed carnivores, experimental assessments should include surveillance and health assessment of domestic and farmed carnivores, characterization of the immune interplay between SARS-CoV-2 and carnivore coronaviruses, determination of the SARS-CoV-2 host range beyond carnivores and identification of human risk groups such as veterinarians and farm workers. Strategies to mitigate the risk of zoonotic SARS-CoV-2 infections may have to be developed in a One Health framework and non-pharmaceutical interventions may have to consider free-roaming animals and the animal farming industry

Specific detection of dengue and Zika virus antibodies using envelope proteins with mutations in the conserved fusion loop

Detection of antibodies is widely used for the diagnosis of infections with arthropod-borne flaviviruses including dengue (DENV) and Zika virus (ZIKV). Due to the emergence of ZIKV in areas endemic for DENV, massive co-circulation is observed and methods to specifically diagnose these infections and differentiate them from each other are mandatory. However, serological assays for flaviviruses in general, and for DENV and ZIKV in particular, are compromised by the high degree of similarities in their proteins which can lead to cross-reacting antibodies and false-positive test results. Cross-reacting flavivirus antibodies mainly target the highly conserved fusion loop (FL) domain in the viral envelope (E-) protein, and we and others have shown previously that recombinant E-proteins bearing FL-mutations strongly reduce cross-reactivity. Here we investigate whether such mutant E-proteins can be used to specifically detect antibodies against DENV and ZIKV in an ELISA-format. IgM antibodies against DENV and ZIKV virus were detected with 100% and 94.2% specificity and 90.7% and 87.5% sensitivity, respectively. For IgG the mutant E-proteins showed cross-reactivity, which was overcome by pre-incubation of the sera with the heterologous antigen. This resulted in specificities of 97.1% and 97.9% and in sensitivities of 100% and 100% for the DENV and ZIKV antigens, respectively. Our results suggest that E-proteins bearing mutations in the FL-domain have a high potential for the development of serological DENV and ZIKV tests with high specificity

Genomic determinants of Furin cleavage in diverse European SARS-related bat coronaviruses

The furin cleavage site (FCS) in SARS-CoV-2 is unique within the Severe acute respiratory syndrome-related coronavirus (SrC) species. We re-assessed diverse SrC from European horseshoe bats and analyzed the spike-encoding genomic region harboring the FCS in SARS-CoV-2. We reveal molecular features in SrC such as purine richness and RNA secondary structures that resemble those required for FCS acquisition in avian influenza viruses. We discuss the potential acquisition of FCS through molecular mechanisms such as nucleotide substitution, insertion, or recombination, and show that a single nucleotide exchange in two European bat-associated SrC may suffice to enable furin cleavage. Furthermore, we show that FCS occurrence is variable in bat- and rodent-borne counterparts of human coronaviruses. Our results suggest that furin cleavage sites can be acquired in SrC via conserved molecular mechanisms known in other reservoir-bound RNA viruses and thus support a natural origin of SARS-CoV-2

Poor Clinical Sensitivity of Rapid Antigen Test for Influenza A Pandemic (H1N1) 2009 Virus

Influenza A pandemic (H1N1) 2009 virus RNA was detected by reverse transcription–PCR in 144 clinical samples from Bonn, Germany. A common rapid antigen–based test detected the virus in only 11.1% of these samples. The paramount feature of rapid test–positive samples was high virus concentration. Antigen-based rapid tests appear unsuitable for virologic diagnostics in the current pandemic

A Click-Chemistry Linked 2’3’-cGAMP Analog

2’3’-cGAMP is an uncanonical cyclic dinucleotide where one A and one G base are connected via a 3’-5’ and a unique 2’-5’ linkage. The molecule is produced by the cyclase cGAS in response to cytosolic DNA binding. cGAMP activates STING and hence one of the most powerful pathways of innate immunity. cGAMP analogs with uncharged linkages that feature better cellular penetrability are currently highly desired. Here, we report the synthesis of a cGAMP analog with one amide and one triazole linkage. The molecule is best prepared via a first Cu(I) catalysed click reaction which establishes the triazole, while the cyclization is achieved by macrolactamization

Rapid decline of Zika virus NS1 antigen-specific antibody responses, northeastern Brazil

Zika virus (ZIKV) is a positive-stranded RNA virus within the Flaviviridae family. After decades of circulation in Asia, ZIKV was introduced to Brazil in 2014–2015, associated with a rise in congenital malformations. Unlike the genetically related dengue virus (DENV), ZIKV constitutes only one serotype. Although assumed that ZIKV infection may engender lifelong immunity, the long-term kinetics of ZIKV antibody responses are unclear. We assessed long-term kinetics of ZIKV NS1-IgG response in 144 individuals from 3 different subpopulations: HIV patients, tuberculosis patients and healthy individuals first tested in 2016 and retested 1.5–2 years after the 2015–2016 ZIKV epidemic in Salvador de Bahia, Brazil, using a widely distributed NS1-based commercial ELISA. The seropositivity in 2016 reached 59.0% (85/144, 95% confidence interval (CI) 50.7–66.7%), and decreased to 38.6% (56/144, CI 31.3–47.0%) 1.5–2 years later. In addition, the median ZIKV NS1-ELISA reactivity for individuals that remained positive in both timepoints significantly decreased from a ratio of 4.4 (95% CI 3.8–5.0) to 1.6 (95% CI 1.6–1.9) over the 2-year interval (Z: − 6.1; p < 0.001) irrespective of the subpopulation analyzed. Initial 2016 DENV antibody response was non-significant between groups, suggesting comparable DENV background. The high 20.6% seroreversion suggest that widely used serologic tests may fail to account a considerable proportion of past ZIKV infections in flavivirus endemic countries. In addition, ZIKV immunity might be shorter-lived than previously thought, which may contribute to local ZIKV resurgence once individual immune responses wane sufficiently to reduce community protective immunity in addition to birth and migration

Identification of animal hosts of Fort Sherman virus, a New World zoonotic orthobunyavirus

An orthobunyavirus termed Fort Sherman virus (FSV) was isolated in 1985 from a febrile US soldier in Panama, yet potential animal reservoirs remained unknown. We investigated sera from 192 clinically healthy peri-domestic animals sampled in northeastern Brazil during 2014–2018 by broadly reactive RT-PCR for orthobunyavirus RNA, including 50 cattle, 57 sheep, 35 goats and 50 horses. One horse sampled in 2018 was positive (0.5%; 95% CI, 0.01–3.2) at 6.2 × 103 viral RNA copies/mL. Genomic comparisons following virus isolation in Vero cells and deep sequencing revealed high identity of translated amino acid sequences between the new orthobunyavirus and the Panamanian FSV prototype (genes: L, 98.8%; M, 83.5%; S, 100%), suggesting these viruses are conspecific. Database comparisons revealed even higher genomic identity between the Brazilian FSV and taxonomically unassigned Argentinian mosquito- and horse-derived viruses sampled in 1965, 1982 and 2013 with only 1.1% maximum translated amino acid distances across viral genes, suggesting the Argentinian viruses were also distinct FSV strains. The Panamanian FSV strain was an M gene reassortant relative to all Southern American FSV strains, clustering phylogenetically with Cache Valley virus (CVV). Mean dN/dS ratios among FSV genes ranged from 0.03 to 0.07, compatible with strong purifying selection. FSV-specific neutralizing antibodies occurred at relatively high end-point titres in the range of 1:300 in 22.0% of horses (11 out of 50 animals), 8.0% of cattle (4/50 animals), 7.0% of sheep (4/57 animals) and 2.9% of goats (1/35 animals). High specificity of serologic testing was suggested by significantly higher overall FSV-specific compared to CVV- and Bunyamwera virus-specific end-point titres (p = .009), corroborating a broad vertebrate host range within peri-domestic animals. Growth kinetics using mosquito-, midge- and sandfly-derived cell lines suggested Aedes mosquitos as potential vectors. Our findings highlight the occurrence of FSV across a geographic range exceeding 7,000 km, surprising genomic conservation across a time span exceeding 50 years, M gene-based reassortment events, and the existence of multiple animal hosts of FSV