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Article: Dengue severity by serotype in 19 years of pediatric clinical studies in Nicaragua.

Narvaez, Federico / Montenegro, Carlos / Juarez, Jose Guillermo / Zambrana, Jose Victor / Gonzalez, Karla / Arguello, Sonia / Barrios, Fanny / Ojeda, Sergio / Plazaola, Miguel / Sanchez, Nery / Camprubi, Daniel / Kuan, Guillermina / Bailey, Gabriela Paz / Harris, Eva / Balmaseda, Angel

medRxiv : the preprint server for health sciences

2024

Abstract: Background: Dengue virus, a major global health threat, consists of four serotypes (DENV1-4) that cause a range of clinical manifestations from mild to severe and potentially fatal disease.: Methods: This study, based on 19 years of data from the ... ...

Abstract	Background: Dengue virus, a major global health threat, consists of four serotypes (DENV1-4) that cause a range of clinical manifestations from mild to severe and potentially fatal disease. Methods: This study, based on 19 years of data from the Pediatric Dengue Cohort Study and Pediatric Dengue Hospital-based Study in Managua, Nicaragua, investigates the influence of serotype and immune status on dengue severity. Study participants 6 months to 17 years old were followed during their hospital stay or as ambulatory patients, with dengue cases confirmed by molecular, serological, and/or virological methods. Results: We enrolled a total of 14071 participants, of whom 2954 (21%) were positive for DENV infection. Of 2425 cases with serotype result by RT-PCR, 541 corresponded to DENV1, 996 to DENV2, 718 to DENV3 and 170 to DENV4. Severe disease was more prevalent among secondary DENV2 and DENV4 cases, while similar disease severity was observed in both primary and secondary DENV1 and DENV3 cases. According to the 1997 World Health Organization (WHO) severity classification, both DENV2 and DENV3 had a higher proportion of severe disease compared to other serotypes, whereas DENV3 had the greatest percentage of severity under the WHO-2009 classification. DENV2 was associated with pleural effusion and low platelet count, while DENV3 correlated with both hypotensive and compensated shock. Conclusions: These findings emphasize the critical need for a dengue vaccine with balanced efficacy against all four serotypes, particularly as existing vaccines show variable efficacy by serotype and immune status, posing challenges for comprehensive protection, particularly in dengue-naïve individuals.
Language	English
Publishing date	2024-02-13
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.11.24302393
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Article ; Online: Humoral correlates of protection against influenza A H3N2 virus infection.

Hoy, Gregory / Stadlbauer, Daniel / Balmaseda, Angel / Kuan, Guillermina / López, Roger / Carreno Quiroz, Juan Manuel / Ojeda, Sergio / Sánchez, Nery / Yellin, Temima / Plazaola, Miguel / Frutos, Aaron / Krammer, Florian / Gordon, Aubree

The Journal of infectious diseases

2024

Abstract: Background: Influenza virus remains a threat to human health, but gaps remain in our knowledge of the humoral correlates of protection against influenza virus A/H3N2, limiting our ability to generate effective, broadly protective vaccines. The role of ... ...

Abstract	Background: Influenza virus remains a threat to human health, but gaps remain in our knowledge of the humoral correlates of protection against influenza virus A/H3N2, limiting our ability to generate effective, broadly protective vaccines. The role of antibodies against the hemagglutinin (HA) stalk, a highly conserved but immunologically sub-dominant region, has not been established for influenza virus A/H3N2. Methods: Household transmission studies were conducted in Managua, Nicaragua across three influenza seasons. Household contacts were tested for influenza virus infection using RT-PCR. We compared pre-existing antibody levels against full-length hemagglutinin (FLHA), HA stalk, and neuraminidase (NA) measured by enzyme-linked immunosorbent assay (ELISA), along with HA inhibition assay (HAI) titers, between infected and uninfected participants. Results: A total of 899 individuals participated in household activation, with 329 infections occurring. A four-fold increase in initial HA stalk titers was independently associated with an 18% decrease in the risk of infection (OR=0.82, 95%CI 0.68-0.98, p=0.04). In adults, anti-HA stalk antibodies were independently associated with protection (OR=0.72, 95%CI 0.54-0.95, p=0.02). However, in 0-14-year-olds, anti-NA antibodies (OR=0.67, 95%CI 0.53-0.85, p<0.01) were associated with protection against infection, but anti-HA stalk antibodies were not. Conclusions: The HA stalk is an independent correlate of protection against A/H3N2 infection, though this association is age dependent. Our results support the continued exploration of the HA stalk as a target for broadly protective influenza vaccines but suggest that the relative benefits may depend on age and influenza virus exposure history.
Language	English
Publishing date	2024-05-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiae258
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Article ; Online: Increased influenza severity in children in the wake of SARS-CoV-2.

Hoy, Gregory / Maier, Hannah E / Kuan, Guillermina / Sánchez, Nery / López, Roger / Meyers, Alyssa / Plazaola, Miguel / Ojeda, Sergio / Balmaseda, Angel / Gordon, Aubree

Influenza and other respiratory viruses

2023 Volume 17, Issue 7, Page(s) e13178

Abstract: The SARS-CoV-2 pandemic and subsequent interruption of influenza circulation has lowered population immunity to influenza, especially among children with few prepandemic exposures. Using data from a prospective pediatric cohort study based in Managua, ... ...

Abstract	The SARS-CoV-2 pandemic and subsequent interruption of influenza circulation has lowered population immunity to influenza, especially among children with few prepandemic exposures. Using data from a prospective pediatric cohort study based in Managua, Nicaragua, we compared the incidence and severity of influenza A/H3N2 and influenza B/Victoria between 2022 and two prepandemic seasons. We found a higher incidence of A/H3N2 in older children in 2022 compared with pre-2020 and a higher proportion of severe influenza in 2022, primarily among children aged 0-4, suggesting an influence of the SARS-CoV-2 pandemic on influenza incidence and severity in children.
MeSH term(s)	Child ; Humans ; Influenza, Human/epidemiology ; SARS-CoV-2 ; Influenza A Virus, H3N2 Subtype ; Cohort Studies ; Prospective Studies ; COVID-19/epidemiology ; Seasons
Language	English
Publishing date	2023-07-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2274538-5
ISSN	1750-2659 ; 1750-2640
ISSN (online)	1750-2659
ISSN	1750-2640
DOI	10.1111/irv.13178
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Article: Increased Influenza Severity in Children in the Wake of SARS-CoV-2.

Hoy, Gregory / Maier, Hannah E / Kuan, Guillermina / Sánchez, Nery / López, Roger / Meyers, Alyssa / Plazaola, Miguel / Ojeda, Sergio / Balmaseda, Angel / Gordon, Aubree

medRxiv : the preprint server for health sciences

2023

Abstract: The SARS-CoV-2 pandemic and subsequent interruption of influenza circulation has lowered population immunity to influenza, especially among children with few pre-pandemic exposures. We compared the incidence and severity of influenza A/H3N2 and influenza ...

Abstract	The SARS-CoV-2 pandemic and subsequent interruption of influenza circulation has lowered population immunity to influenza, especially among children with few pre-pandemic exposures. We compared the incidence and severity of influenza A/H3N2 and influenza B/Victoria between 2022 and two pre-pandemic seasons and found an increased frequency of severe influenza in 2022.
Language	English
Publishing date	2023-03-16
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.11.23286858
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Article ; Online: Infection-Induced Immunity Is Associated With Protection Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Decreased Infectivity.

Frutos, Aaron M / Kuan, Guillermina / Lopez, Roger / Ojeda, Sergio / Shotwell, Abigail / Sanchez, Nery / Saborio, Saira / Plazaola, Miguel / Barilla, Carlos / Kenah, Eben / Balmaseda, Angel / Gordon, Aubree

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2023 Volume 76, Issue 12, Page(s) 2126–2133

Abstract: Background: The impact of infection-induced immunity on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has not been well established. Here we estimate the effects of prior infection induced immunity in adults and children on ... ...

Abstract	Background: The impact of infection-induced immunity on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has not been well established. Here we estimate the effects of prior infection induced immunity in adults and children on SARS-CoV-2 transmission in households. Methods: We conducted a household cohort study from March 2020-November 2022 in Managua, Nicaragua; following a housheold SARS-CoV-2 infection, household members are closely monitored for infection. We estimate the association of time period, age, symptoms, and prior infection with secondary attack risk. Results: Overall, transmission occurred in 70.2% of households, 40.9% of household contacts were infected, and the secondary attack risk ranged from 8.1% to 13.9% depending on the time period. Symptomatic infected individuals were more infectious (rate ratio [RR] 21.2, 95% confidence interval [CI]: 7.4-60.7) and participants with a prior infection were half as likely to be infected compared to naïve individuals (RR 0.52, 95% CI:.38-.70). In models stratified by age, prior infection was associated with decreased infectivity in adults and adolescents (secondary attack risk [SAR] 12.3, 95% CI: 10.3, 14.8 vs 17.5, 95% CI: 14.8, 20.7). However, although young children were less likely to transmit, neither prior infection nor symptom presentation was associated with infectivity. During the Omicron era, infection-induced immunity remained protective against infection. Conclusions: Infection-induced immunity is associated with decreased infectivity for adults and adolescents. Although young children are less infectious, prior infection and asymptomatic presentation did not reduce their infectivity as was seen in adults. As SARS-CoV-2 transitions to endemicity, children may become more important in transmission dynamics.
MeSH term(s)	Adult ; Child ; Adolescent ; Humans ; Child, Preschool ; COVID-19 ; SARS-CoV-2 ; Cohort Studies ; Family Characteristics ; Nicaragua/epidemiology
Language	English
Publishing date	2023-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciad074
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Article: High co-circulation of influenza and SARS-CoV-2.

Kubale, John T / Frutos, Aaron M / Balmaseda, Angel / Saborio, Saira / Ojeda, Sergio / Barilla, Carlos / Sanchez, Nery / Shotwell, Abigail / Meyers, Alyssa / Lopez, Roger / Plazaola, Miguel / Kuan, Guillermina / Gordon, Aubree

medRxiv : the preprint server for health sciences

2022

Abstract: In the first two years of the COVID-19 pandemic, influenza transmission decreased substantially worldwide meaning that health systems were not faced with simultaneous respiratory epidemics. In 2022, however, substantial influenza transmission returned to ...

Abstract	In the first two years of the COVID-19 pandemic, influenza transmission decreased substantially worldwide meaning that health systems were not faced with simultaneous respiratory epidemics. In 2022, however, substantial influenza transmission returned to Nicaragua where it co-circulated with SARS-CoV-2 causing substantial disease burden.
Language	English
Publishing date	2022-09-17
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.09.13.22279740
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Article: SARS-CoV-2 and endemic coronaviruses: Comparing symptom presentation and severity of symptomatic illness among Nicaraguan children.

Frutos, Aaron M / Kubale, John / Kuan, Guillermina / Ojeda, Sergio / Vydiswaran, Nivea / Sanchez, Nery / Plazaola, Miguel / Patel, May / Lopez, Roger / Balmaseda, Angel / Gordon, Aubree

medRxiv : the preprint server for health sciences

2022

Abstract: It has been proposed that as SARS-CoV-2 transitions to endemicity, children will represent the greatest proportion of SARS-Co-V-2 infections as they currently do with endemic coronavirus infections. While SARS-CoV-2 infection severity is low for children, ...

Abstract	It has been proposed that as SARS-CoV-2 transitions to endemicity, children will represent the greatest proportion of SARS-Co-V-2 infections as they currently do with endemic coronavirus infections. While SARS-CoV-2 infection severity is low for children, it is unclear if SARS-CoV-2 infections are distinct in symptom presentation, duration, and severity from endemic coronavirus infections in children. We compared symptom risk and duration of endemic human coronavirus (HCoV) infections from 2011-2016 with SARS-CoV-2 infections from March 2020-September 2021 in a Nicaraguan pediatric cohort. Blood samples were collected from study participants annually in February-April. Respiratory samples were collected from participants that met testing criteria. Blood samples collected in were tested for SARS-CoV-2 antibodies and a subset of 2011-2016 blood samples from four-year-old children were tested for endemic HCoV antibodies. Respiratory samples were tested for each of the endemic HCoVs from 2011-2016 and for SARS-CoV-2 from 2020-2021 via rt-PCR. By April 2021, 854 (49%) cohort participants were ELISA positive for SARS-CoV-2 antibodies. Most participants had antibodies against one alpha and one beta coronavirus by age four. We observed 595 symptomatic endemic HCoV infections from 2011-2016 and 121 symptomatic with SARS-CoV-2 infections from March 2020-September 2021. Symptom presentation of SARS-CoV-2 infection and endemic coronavirus infections were very similar, and SARS-CoV-2 symptomatic infections were as or less severe on average than endemic HCoV infections. This suggests that, for children, SARS-CoV-2 may be just another endemic coronavirus. However, questions about the impact of variants and the long-term effects of SARS-CoV-2 remain.
Language	English
Publishing date	2022-02-03
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.12.09.21267537
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Article: Infection-induced immunity is associated with protection against SARS-CoV-2 infection, but not decreased infectivity during household transmission.

medRxiv : the preprint server for health sciences

2022

Abstract: Background: Understanding the impact of infection-induced immunity on SARS-CoV-2 transmission will provide insight into the transition of SARS-CoV-2 to endemicity. Here we estimate the effects of prior infection induced immunity and children on SARS-CoV- ...

Abstract	Background: Understanding the impact of infection-induced immunity on SARS-CoV-2 transmission will provide insight into the transition of SARS-CoV-2 to endemicity. Here we estimate the effects of prior infection induced immunity and children on SARS-CoV-2 transmission in households. Methods: We conducted a household cohort study between March 2020-June 2022 in Managua, Nicaragua where when one household member tests positive for SARS-CoV-2, household members are closely monitored for SARS-CoV-2 infection. Using a pairwise survival model, we estimate the association of infection period, age, symptoms, and infection-induced immunity with secondary attack risk. Results: Overall transmission occurred in 72.4% of households, 42% of household contacts were infected and the secondary attack risk was 13.0% (95% CI: 11.7, 14.6). Prior immunity did not impact the probability of transmitting SARS-CoV-2. However, participants with pre-existing infection-induced immunity were half as likely to be infected compared to naïve individuals (RR 0.53, 95% CI: 0.39, 0.72), but this reduction was not observed in children. Likewise, symptomatic infected individuals were more likely to transmit (RR 24.4, 95% CI: 7.8, 76.1); however, symptom presentation was not associated with infectivity of young children. Young children were less likely to transmit SARS-CoV-2 than adults. During the omicron era, infection-induced immunity remained protective against infection. Conclusions: Infection-induced immunity is associated with protection against infection for adults and adolescents. While young children are less infectious, prior infection and asymptomatic presentation did not reduce their infectivity as was seen in adults. As SARS-CoV-2 transitions to endemicity, children may become more important in transmission dynamics. Article summary: Infection-induced immunity protects against SARS-CoV-2 infection for adolescents and adults; however, there was no protection in children. Prior immunity in an infected individual did not impact the probability they will spread SARS-CoV-2 in a household setting.
Language	English
Publishing date	2022-10-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.10.10.22280915
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Article ; Online: Protection Associated with Previous SARS-CoV-2 Infection in Nicaragua.

Maier, Hannah E / Balmaseda, Angel / Saborio, Saira / Ojeda, Sergio / Barilla, Carlos / Sanchez, Nery / Lopez, Roger / Plazaola, Miguel / Cerpas, Cristhiam / van Bakel, Harm / Kubale, John / Harris, Eva / Kuan, Guillermina / Gordon, Aubree

The New England journal of medicine

2022 Volume 387, Issue 6, Page(s) 568–570

MeSH term(s)	Antibodies, Viral/immunology ; COVID-19/immunology ; Humans ; Immunity, Active/immunology ; Nicaragua/epidemiology ; SARS-CoV-2
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2022-07-20
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2203985
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Article ; Online: SARS-CoV-2 and endemic coronaviruses: Comparing symptom presentation and severity of symptomatic illness among Nicaraguan children.

Frutos, Aaron M / Kubale, John / Kuan, Guillermina / Ojeda, Sergio / Vydiswaran, Nivea / Sanchez, Nery / Plazaola, Miguel / Patel, May / Lopez, Roger / Balmaseda, Angel / Gordon, Aubree

PLOS global public health

2022 Volume 2, Issue 5

Abstract	It has been proposed that as SARS-CoV-2 transitions to endemicity, children will represent the greatest proportion of SARS-Co-V-2 infections as they currently do with endemic coronavirus infections. While SARS-CoV-2 infection severity is low for children, it is unclear if SARS-CoV-2 infections are distinct in symptom presentation, duration, and severity from endemic coronavirus infections in children. We compared symptom risk and duration of endemic human coronavirus (HCoV) infections from 2011-2016 with SARS-CoV-2 infections from March 2020-September 2021 in a Nicaraguan pediatric cohort. Blood samples were collected from study participants annually in February-April. Respiratory samples were collected from participants that met testing criteria. Blood samples collected in were tested for SARS-CoV-2 antibodies and a subset of 2011-2016 blood samples from four-year-old children were tested for endemic HCoV antibodies. Respiratory samples were tested for each of the endemic HCoVs from 2011-2016 and for SARS-CoV-2 from 2020-2021 via rt-PCR. By April 2021, 854 (49%) cohort participants were ELISA positive for SARS-CoV-2 antibodies. Most participants had antibodies against one alpha and one beta coronavirus by age four. We observed 595 symptomatic endemic HCoV infections from 2011-2016 and 121 symptomatic with SARS-CoV-2 infections from March 2020-September 2021. Symptom presentation of SARS-CoV-2 infection and endemic coronavirus infections were very similar, and SARS-CoV-2 symptomatic infections were as or less severe on average than endemic HCoV infections. This suggests that, for children, SARS-CoV-2 may be just another endemic coronavirus. However, questions about the impact of variants and the long-term effects of SARS-CoV-2 remain.
Language	English
Publishing date	2022-05-25
Publishing country	United States
Document type	Journal Article
ISSN	2767-3375
ISSN (online)	2767-3375
DOI	10.1371/journal.pgph.0000414
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