Risk factors associated with severe COVID-19 outcomes in Jamaica: a cross-sectional study of national surveillance data.

Objectives: To describe the characteristics and outcomes of COVID-19 cases in Jamaica and to explore the risk factors associated with severe COVID-19 from 9 March to 31 December 2020. Methods: A cross-sectional analysis of national surveillance data was conducted using confirmed COVID-19 cases in Jamaica. Definitions of a confirmed case, disease severity, and death were based on World Health Organization guidelines. Chi-square and Fisher exact tests were used to determine association with outcomes. Logistic regression models were used to determine predictors of severe COVID-19. Results: This analysis included 12 169 cases of COVID-19 (median age, 36 years; 6 744 females [ 55.4%]) of which 512 cases (4.2%) presented with severe disease, and of those, 318 patients (62.1%) died (median age at death, 71.5 years). Severe disease was associated with being male (OR 1.4; 95% CI, 1.2-1.7) and 40 years or older (OR, 6.5; 95% CI, 5.1-8.2). COVID-19 death was also associated with being male (OR, 1.4; 95% CI, 1.1-1.7), age 40 years or older (OR, 17.9; 95% CI, 11.6-27.7), and in the Western versus South East Health Region (OR 1.7; 95% CI, 1.2-2.3). Conclusions: The findings of this cross-sectional analysis indicate that confirmed cases of COVID-19 in Jamaica were more likely to be female and younger individuals, whereas COVID-19 deaths occurred more frequently in males and older individuals. There is increased risk of poor COVID-19 outcomes beginning at age 40, with males disproportionately affected. COVID-19 death also varied by geographic region. This evidence could be useful to other countries with similar settings and to policymakers charged with managing outbreaks and health.

Risk factors associated with severe COVID-19 outcomes in Jamaica: a cross-sectional study of national surveillance data / Factores de riesgo asociados a la COVID-19 grave en Jamaica: estudio transversal de datos nacionales de vigilancia / Fatores de risco associados a desfechos graves da COVID-19 na Jamaica: estudo transversal de dados de vigilância nacional

[ABSTRACT]. Objectives. To describe the characteristics and outcomes of COVID-19 cases in Jamaica and to explore the risk factors associated with severe COVID-19 from 9 March to 31 December 2020. Methods. A cross-sectional analysis of national surveillance data was conducted using confirmed COVID-19 cases in Jamaica. Definitions of a confirmed case, disease severity, and death were based on World Health Organization guidelines. Chi-square and Fisher exact tests were used to determine association with outcomes. Logistic regression models were used to determine predictors of severe COVID-19. Results. This analysis included 12 169 cases of COVID-19 (median age, 36 years; 6 744 females [ 55.4%]) of which 512 cases (4.2%) presented with severe disease, and of those, 318 patients (62.1%) died (median age at death, 71.5 years). Severe disease was associated with being male (OR 1.4; 95% CI, 1.2-1.7) and 40 years or older (OR, 6.5; 95% CI, 5.1-8.2). COVID-19 death was also associated with being male (OR, 1.4; 95% CI, 1.1-1.7), age 40 years or older (OR, 17.9; 95% CI, 11.6-27.7), and in the Western versus South East Health Region (OR 1.7; 95% CI, 1.2-2.3). Conclusions. The findings of this cross-sectional analysis indicate that confirmed cases of COVID-19 in Jamaica were more likely to be female and younger individuals, whereas COVID-19 deaths occurred more frequently in males and older individuals. There is increased risk of poor COVID-19 outcomes beginning at age 40, with males disproportionately affected. COVID-19 death also varied by geographic region. This evidence could be useful to other countries with similar settings and to policymakers charged with managing outbreaks and health.

[RESUMEN]. Objetivos. Describir las características y los resultados de los casos de COVID-19 en Jamaica y explorar los factores de riesgo asociados a la COVID-19 grave desde el 9 de marzo hasta el 31 de diciembre del 2020. Métodos. Se realizó un análisis transversal de datos nacionales de vigilancia a partir de los casos confirma- dos de COVID-19 en Jamaica. Las definiciones de caso confirmado, gravedad de la enfermedad y muerte se basaron en las directrices de la Organización Mundial de la Salud. Para determinar la asociación con los criterios de valoración se utilizó la prueba de χ2 y la prueba exacta de Fisher. Se usaron modelos de regresión logística para determinar los factores predictivos de la COVID-19 grave. Resultados. Se incluyeron en el análisis 12 169 casos de COVID-19 (mediana de edad, 36 años; 6 744 mujeres [55,4%]), de los que 512 (4,2%) fueron de enfermedad grave. De estos pacientes, 318 (62,1%) fall- ecieron (mediana de edad al morir, 71,5 años). Se observó una asociación de la enfermedad grave con el sexo masculino (OR de 1,4; IC del 95 %, 1,2-1,7) y con la edad igual o superior a 40 años (OR de 6,5; IC del 95 %, 5,1-8,2). La muerte por COVID-19 también mostró una asociación con el sexo masculino (OR de 1,4; IC del 95%, 1,1-1,7), con la edad igual o superior a 40 años (OR de 17,9; IC del 95%, 11,6-27,7) y con la Región de Atención de Salud Occidental en comparación con la Sudoriental (OR de 1,7; IC del 95%, 1,2-2,3). Conclusiones. Los resultados de este análisis transversal indican que los casos confirmados de COVID-19 en Jamaica correspondieron una mayor probabilidad a mujeres y personas más jóvenes, mientras que las muertes por COVID-19 fueron más frecuentes en varones y personas de mayor edad. Hay un mayor riesgo de evolución desfavorable de la COVID-19 a partir de los 40 años, que afecta de manera desproporcionada a los varones. Las muertes por COVID-19 también variaron según la región geográfica. Esta evidencia podría ser de utilidad para otros países con entornos similares y para los responsables de la formulación de políticas en materia de gestión de brotes y salud.

[RESUMO]. Objetivos. Descrever as características e os desfechos dos casos de COVID-19 na Jamaica e explorar os fatores de risco associados à COVID-19 grave de 9 de março a 31 de dezembro de 2020. Métodos. Análise transversal de dados de vigilância nacional usando casos confirmados de COVID-19 na Jamaica. As definições de caso confirmado, gravidade da doença e morte foram baseadas nas recomendações da Organização Mundial da Saúde. Foram usados testes de qui-quadrado e exato de Fisher para determinar a associação com os desfechos. Modelos de regressão logística foram usados para deter- minar os preditores de COVID-19 grave. Resultados. Esta análise incluiu 12.169 casos de COVID-19 (idade mediana: 36 anos; 6 744 do sexo feminino [55,4%]), dos quais 512 casos (4,2%) apresentaram doença grave; desses, 318 pacientes (62,1%) morreram (idade mediana ao morrer: 71,5 anos). A doença grave estava associada a ser do sexo masculino (razão de chances [RC]: 1,4; intervalo de confiança de 95% [IC 95%]: 1,2–1,7) e ter 40 anos ou mais de idade (RC: 6,5; IC 95%: 5,1–8,2). A morte por COVID-19 também estava associada a ser sexo masculino (RC: 1,4; IC 95%: 1,1–1,7), ter 40 anos ou mais (RC: 17,9; IC 95%: 11,6–27,7) e estar na Região Sanitária Oeste em comparação com a Região Sanitária Sudeste (RC: 1,7; IC 95%: 1,2–2,3). Conclusões. Os achados desta análise transversal indicam que a probabilidade de casos confirmados de COVID-19 na Jamaica era maior em indivíduos do sexo feminino e mais jovens, ao passo que as mortes por COVID-19 ocorreram com mais frequência em indivíduos do sexo masculino e mais velhos. Há um risco maior de resultados desfavoráveis em relação à COVID-19 a partir dos 40 anos, e indivíduos do sexo masculino são desproporcionalmente mais afetados. A morte por COVID-19 também variou de acordo com a região geográ- fica. Essas evidências podem ser úteis para outros países com cenários semelhantes e para os formuladores de políticas encarregados de manejar surtos e gerenciar a saúde.

Compensatory substitutions restore normal core assembly in simian immunodeficiency virus isolates with Gag epitope cytotoxic T-lymphocyte escape mutations.

The evolution of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) as they replicate in infected individuals reflects a balance between the pressure on the virus to mutate away from recognition by dominant epitope-specific cytotoxic T lymphocytes (CTL) and the structural constraints on the virus' ability to mutate. To gain a further understanding of the strategies employed by these viruses to maintain replication competency in the face of the intense selection pressure exerted by CTL, we have examined the replication fitness and morphological ramifications of a dominant epitope mutation and associated flanking amino acid substitutions on the capsid protein (CA) of SIV/simian-human immunodeficiency virus (SHIV). We show that a residue 2 mutation in the immunodominant p11C, C-M epitope (T47I) of SIV/SHIV not only decreased CA protein expression and viral replication, but it also blocked CA assembly in vitro and virion core condensation in vivo. However, these defects were restored by the introduction of upstream I26V and/or downstream I71V substitutions in CA. These findings demonstrate how flanking compensatory amino acid substitutions can facilitate viral escape from a dominant epitope-specific CTL response through the effects of these associated mutations on the structural integrity of SIV/SHIV.

Comparative evaluation of three different intramuscular delivery methods for DNA immunization in a nonhuman primate animal model.

Although plasmid DNA vaccines induce potent cell-mediated immune responses and prime for antibody responses in experimental laboratory animals, their immunogenicity in humans has been less remarkable. A number of strategies have been proposed to improve the immunogenicity of these vaccines, including using novel means of vaccine delivery. In the present study, the immunogenicity of three different methods of intramuscular plasmid DNA administration was compared in cynomolgus monkeys: needle and syringe, Biojector 2000, and Mini-Ject. The elicited cellular and humoral immune responses were comparable in monkeys immunized using these different delivery techniques, suggesting that the needle-free approaches to vaccine administration do not significantly improve the immunogenicity of the plasmid DNA vaccine used in the study.

Replication-defective adenovirus serotype 5 vectors elicit durable cellular and humoral immune responses in nonhuman primates.

The magnitude and durability of immune responses induced by replication-defective adenovirus serotype 5 (ADV5) vector-based vaccines were evaluated in the simian-human immunodeficiency virus/rhesus monkey model. A single inoculation of recombinant ADV5 vector constructs induced cellular and humoral immunity, but the rapid generation of neutralizing anti-Ad5 antibodies limited the immunity induced by repeated vector administration. The magnitude and durability of the immune responses elicited by these vaccines were greater when they were delivered as boosting immunogens in plasmid DNA-primed monkeys than when they were used as single-modality immunogens. Therefore, administration of ADV5-based vectors in DNA-primed subjects may be a preferred use of this vaccine modality for generating long-term immune protection.

Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants.

Viral escape from cytotoxic T lymphocytes (CTLs) can undermine immune control of human immunodeficiency virus 1. It is therefore important to assess the stability of viral mutations in CTL epitopes after transmission to naive hosts. Here we demonstrate the persistence of mutations in a dominant CTL epitope after transmission of simian immunodeficiency virus variants to major histocompatibility complex-matched rhesus monkeys. Transient reversions to wild-type sequences occurred and elicited CTLs specific for the wild-type epitope, resulting in immunological pressure that rapidly reselected the mutant viruses. These data suggest that mutations in dominant human immunodeficiency virus 1 CTL epitopes may accumulate in human populations with limited major histocompatibility complex heterogeneity by a mechanism involving dynamic CTL control of transiently reverted wild-type virus.

Novel adeno-associated virus vector vaccine restricts replication of simian immunodeficiency virus in macaques.

Gene transfer vectors based on recombinant adeno-associated virus (rAAV) are simple, versatile, and safe. While the conventional applications for rAAV vectors have focused on delivery of therapeutic genes, we have developed the system for delivery of vaccine antigens. In particular, we are interested in generating rAAV vectors for use as a prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine. To that end, we constructed vaccine vectors that expressed genes from the simian immunodeficiency virus (SIV) for evaluation in the monkey SIV model. After a single intramuscular dose, rAAV/SIV vaccines elicited SIV-specific T cells and antibodies in macaques. Furthermore, immunized animals were able to significantly restrict replication of a live, virulent SIV challenge. These data suggest that rAAV vaccine vectors induced biologically relevant immune responses, and thus, warrant continued development as a viable HIV-1 vaccine candidate.

Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not memory T lymphocyte responses.

Although a consensus has emerged that an HIV vaccine should elicit a cytotoxic T lymphocyte (CTL) response, the characteristics of an effective vaccine-induced T lymphocyte response remain unclear. We explored this issue in the simian human immunodeficiency virus/rhesus monkey model in the course of assessing the relative immunogenicity of vaccine regimens that included a cytokine-augmented plasmid DNA prime and a boost with DNA or recombinant pox vectors. Recombinant vaccinia virus, recombinant modified vaccinia Ankara (MVA), and recombinant fowlpox were comparable in their immunogenicity. Moreover, whereas the magnitude of the peak vaccine-elicited T lymphocyte responses in the recombinant pox virus-boosted monkeys was substantially greater than that seen in the monkeys immunized with plasmid DNA alone, the magnitudes of recombinant pox boosted CTL responses decayed rapidly and were comparable to those of the DNA-alone-vaccinated monkeys by the time of viral challenge. Consistent with these comparable memory T cell responses, the clinical protection seen in all groups of experimentally vaccinated monkeys was similar. This study, therefore, indicates that the steady-state memory, rather than the peak effector vaccine-elicited T lymphocyte responses, may be the critical immune correlate of protection for a CTL-based HIV vaccine.

A simian immunodeficiency virus nef peptide is a dominant cytotoxic T lymphocyte epitope in Indian-origin rhesus monkeys expressing the common MHC class I allele mamu-A*02.

The precise measurement of epitope-specific cytotoxic T lymphocyte (CTL) responses in simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infected or vaccinated rhesus monkeys has been important in the evaluation of potential HIV vaccine strategies. This quantitation of CTL has been limited to date by the identification of only one dominant SIV/SHIV epitope in these monkeys. We have recently defined a Nef CTL epitope p199RY (YTSGPGIRY) that is recognized by CD8(+) T lymphocytes from all SIV/SHIV-infected Mamu-A*02(+) rhesus monkeys that have been evaluated. We now measure the frequency of p199RY-specific CD8(+) T lymphocytes in the peripheral blood of these monkeys with quantitative precision, using MHC class I/peptide tetramer staining and peptide-stimulated interferon-gamma Elispot assays. These epitope-specific CD8(+) T lymphocytes are present at a very high frequency and represent a significant proportion of the entire SIV- or SHIV-specific CD8(+) T lymphocyte population in SIV/SHIV-infected Mamu-A*02(+) rhesus monkeys. Knowledge of this dominant CTL epitope should prove valuable in the evaluation of HIV vaccine strategies using this animal model.

Prior vaccination increases the epitopic breadth of the cytotoxic T-lymphocyte response that evolves in rhesus monkeys following a simian-human immunodeficiency virus infection.

Although recent evidence has confirmed the importance of cytotoxic T-lymphocyte (CTL) responses in controlling human immunodeficiency virus type 1 and simian immunodeficiency virus replication, the relevance of the epitopic breadth of those CTL responses remains unexplored. In the present study, we sought to determine whether vaccination can expand CTL populations which recognize a repertoire of viral epitopes that is greater than is typically generated in the course of a viral infection. We demonstrate that potent secondary CTL responses to subdominant epitopes are rapidly generated following a pathogenic simian-human immunodeficiency virus challenge of rhesus monkeys vaccinated with plasmid DNA or recombinant modified vaccinia virus Ankara vaccines. These data indicate that prior vaccination can increase the breadth of the CTL response that evolves after an AIDS virus infection.

Recombinant canarypox vaccine-elicited CTL specific for dominant and subdominant simian immunodeficiency virus epitopes in rhesus monkeys.

Since virus-specific CTL play a central role in containing HIV replication, a candidate AIDS vaccine should generate virus-specific CTL responses. In this study, the ability of a recombinant canarypox virus expressing SIV Gag-Pol-Env (ALVAC/SIV gag-pol-env) was assessed for its ability to elicit both dominant and subdominant epitope-specific CTL responses in rhesus monkeys. Following a series of five immunizations, memory CTL responses specific for a dominant Gag epitope could be demonstrated in the peripheral blood of vaccinated monkeys. Memory CTL responses to a subdominant Pol epitope were undetectable in these animals. Following challenge with SIVmac251, the experimentally vaccinated animals developed high frequency CTL responses specific for the dominant Gag epitope that emerged in temporal association with the early containment of viral replication. Interestingly, the experimentally vaccinated, but not the control vaccinated animals, developed CTL responses to the subdominant Pol epitope that were detectable only after containment of early viremia. Thus, recombinant canarypox vaccination elicited low frequency, but durable memory CTL populations. The temporal association of the emergence of the dominant epitope-specific response with early viral containment following challenge suggests that this immune response played a role in the accelerated clearing of early viremia in these animals. The later emerging CTL response specific for the subdominant epitope may contribute to the control of viral replication in the setting of chronic infection.