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2.
PLOS global public health ; 2(5), 2022.
Article in English | EuropePMC | ID: covidwho-1918645

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.

3.
Nature ; 607(7917): 119-127, 2022 07.
Article in English | MEDLINE | ID: covidwho-1915276

ABSTRACT

The recent emergence of SARS-CoV-2 Omicron (B.1.1.529 lineage) variants possessing numerous mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies and antiviral drugs for COVID-19 against these variants1,2. The original Omicron lineage, BA.1, prevailed in many countries, but more recently, BA.2 has become dominant in at least 68 countries3. Here we evaluated the replicative ability and pathogenicity of authentic infectious BA.2 isolates in immunocompetent and human ACE2-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone4, we observed similar infectivity and pathogenicity in mice and hamsters for BA.2 and BA.1, and less pathogenicity compared with early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from individuals who had recovered from COVID-19 and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987 plus REGN10933, COV2-2196 plus COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir and S-217622) can restrict viral infection in the respiratory organs of BA.2-infected hamsters. These findings suggest that the replication and pathogenicity of BA.2 is similar to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and antiviral compounds are effective against Omicron BA.2 variants.


Subject(s)
Antiviral Agents , COVID-19/drug therapy , SARS-CoV-2 , Animals , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing/pharmacology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/pharmacology , Antibodies, Viral/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/genetics , COVID-19/immunology , COVID-19/virology , Cricetinae , Cytidine/analogs & derivatives , Drug Combinations , Hydroxylamines , Indazoles , Lactams , Leucine , Mice , Nitriles , Proline , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Triazines , Triazoles
4.
JAMA Netw Open ; 5(6): e2218794, 2022 06 01.
Article in English | MEDLINE | ID: covidwho-1905757

ABSTRACT

Importance: The impact of the SARS-CoV-2 pandemic on children remains unclear. Better understanding of the burden of COVID-19 among children and their risk of reinfection is crucial, as they will be among the last groups vaccinated. Objective: To characterize the burden of COVID-19 and assess how risk of symptomatic reinfection may vary by age among children. Design, Setting, and Participants: In this prospective, community-based pediatric cohort study conducted from March 1, 2020, to October 15, 2021, 1964 nonimmunocompromised children aged 0 to 14 years were enrolled by random selection from the Nicaraguan Pediatric Influenza Cohort, a community-based cohort in District 2 of Managua, Nicaragua. Additional newborn infants aged 4 weeks or younger were randomly selected and enrolled monthly via home visits. Exposures: Prior COVID-19 infection as confirmed by positive anti-SARS-CoV-2 antibodies (receptor binding domain and spike protein) or real-time reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 infection at least 60 days before current COVID-19 infection. Main Outcomes and Measures: Symptomatic COVID-19 cases confirmed by real-time RT-PCR and hospitalization within 28 days of symptom onset of a confirmed COVID-19 case. Results: This cohort study assessed 1964 children (mean [SD] age, 6.9 [4.4] years; 985 [50.2%] male). Of 1824 children who were tested, 908 (49.8%; 95% CI, 47.5%-52.1%) were seropositive during the study. There were also 207 PCR-confirmed COVID-19 cases, 12 (5.8%) of which were severe enough to require hospitalization. Incidence of COVID-19 was highest among children younger than 2 years (16.1 cases per 100 person-years; 95% CI, 12.5-20.5 cases per 100 person-years), which was approximately 3 times the incidence rate in any other child age group assessed. In addition, 41 symptomatic SARS-CoV-2 episodes (19.8%; 95% CI, 14.4%-25.2%) were reinfections. Conclusions and Relevance: In this prospective, community-based pediatric cohort study, rates of symptomatic and severe COVID-19 were highest among the youngest participants, with rates stabilizing at approximately 5 years of age. In addition, symptomatic reinfections represented a large proportion of symptomatic COVID-19 cases.


Subject(s)
COVID-19 , SARS-CoV-2 , Adolescent , COVID-19/epidemiology , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Nicaragua/epidemiology , Prospective Studies , Reinfection
5.
Vaccines (Basel) ; 10(5)2022 May 20.
Article in English | MEDLINE | ID: covidwho-1875823

ABSTRACT

Longitudinal data comparing SARS-CoV-2 serology in individuals following infection and vaccination over 12 months are limited. This study compared the magnitude, decay, and variability in serum IgG, IgA, and neutralizing activity induced by natural infection (n = 218) or mRNA vaccination in SARS-CoV-2 naïve (n = 143) or experienced (n = 122) individuals over time using enzyme-linked immunosorbent assays and an in vitro virus neutralization assay. Serological responses were found to be highly variable after natural infection compared with vaccination but durable through 12 months. Antibody levels in vaccinated, SARS-CoV-2 naïve individuals peaked by 1 month then declined through 9 months, culminating in non-detectable SARS-CoV-2-specific serum IgA. Individuals with both infection and vaccination showed SARS-CoV-2-specific IgG and IgA levels that were more robust and slower to decline than the other groups; neutralizing activity remained highest in this group at 9 months past vaccination. These data reinforce the benefit of vaccination after SARS-CoV-2 recovery.

6.
Lancet ; 399(10340): 2047-2064, 2022 05 28.
Article in English | MEDLINE | ID: covidwho-1864651

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).


Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Child , Child, Preschool , Cost of Illness , Global Health , Hospital Mortality , Hospitalization , Humans , Infant , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Tract Infections/epidemiology
7.
mSphere ; 7(3): e0017922, 2022 06 29.
Article in English | MEDLINE | ID: covidwho-1854243

ABSTRACT

To understand reinfection rates and correlates of protection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we established eight different longitudinal cohorts in 2020 under the umbrella of the PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2)/SPARTA (SARS SeroPrevalence And Respiratory Tract Assessment) studies. Here, we describe the PARIS/SPARTA cohorts, the harmonized assays and analysis that are performed across the cohorts, as well as case definitions for SARS-CoV-2 infection and reinfection that have been established by the team of PARIS/SPARTA investigators. IMPORTANCE Determining reinfection rates and correlates of protection against SARS-CoV-2 infection induced by both natural infection and vaccination is of high significance for the prevention and control of coronavirus disease 2019 (COVID-19). Furthermore, understanding reinfections or infection after vaccination and the role immune escape plays in these scenarios will inform the need for updates of the current SARS-CoV-2 vaccines and help update guidelines suitable for the postpandemic world.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Vaccines , Humans , Reinfection , Seroepidemiologic Studies
8.
Sci Transl Med ; 14(657): eabm4908, 2022 Aug 10.
Article in English | MEDLINE | ID: covidwho-1846321

ABSTRACT

The SARS-CoV-2 B.1.621 (Mu) variant emerged in January 2021 and was categorized as a variant of interest by the World Health Organization in August 2021. This designation prompted us to study the sensitivity of this variant to antibody neutralization. In a live virus neutralization assay with serum samples from individuals vaccinated with the Pfizer/BioNTech or Moderna mRNA vaccines, we measured neutralization antibody titers against B.1.621, an early isolate (spike 614D), and a variant of concern (B.1.351, Beta variant). We observed reduced neutralizing antibody titers against the B.1.621 variant (3.4- to 7-fold reduction, depending on the serum sample and time after the second vaccination) compared to the early isolate and a similar reduction when compared to B.1.351. Likewise, convalescent serum from hamsters previously infected with an early isolate neutralized B.1.621 to a lower degree. Despite this antibody titer reduction, hamsters could not be efficiently rechallenged with the B.1.621 variant, suggesting that the immune response to the first infection is adequate to provide protection against a subsequent infection with the B.1.621 variant.


Subject(s)
COVID-19 , Viral Envelope Proteins , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive , Membrane Glycoproteins/genetics , Neutralization Tests , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Vaccination , Viral Envelope Proteins/genetics
9.
Front Pediatr ; 9: 752993, 2021.
Article in English | MEDLINE | ID: covidwho-1779952

ABSTRACT

Objectives: Studies of household transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) focused on households with children are limited. We investigated household secondary attack rate (SAR), transmission dynamics, and contributing factors in households with children. Materials and Methods: In this prospective case-ascertained study in Los Angeles County, California, all households members were enrolled if ≥1 member tested positive for SARS-CoV-2 by polymerase chain reaction (PCR). Nasopharyngeal PCRs, serology, and symptom data were obtained over multiple visits. Results: A total of 489 individuals in 105 households were enrolled from June to December 2020. The majority (77.3%) reported a household annual income of <$50,000, and most (92.9%) were of Hispanic/Latinx ethnicity. Children <18 years old accounted for 46.9% index cases, of whom 45.3% were asymptomatic. Household index cases were predominantly children during low community transmission and adults during the high community transmission period (χ2 = 7.647, p = 0.0036. The mean household SAR was 77.0% (95% CI: 69.4-84.6%). Child and adult index cases both efficiently transmitted SARS-CoV-2 within households [81.9%, (95% CI: 72.1-91.9%) vs. 72.4% (95% CI: 59.8-85.1%), p = 0.23]. Household income and pets were significantly associated with higher SAR in the multivariable analysis of household factors (p = 0.0013 and 0.004, respectively). Conclusions: The SAR in households with children in an urban setting with a large ethnic minority population is much higher than previously described. Children play important roles as index cases. SAR was disproportionately impacted by household income. Vaccination and public health efforts need special focus on children and vulnerable communities to help mitigate SARS-CoV-2 spread.

10.
Nature ; 605(7911): 640-652, 2022 05.
Article in English | MEDLINE | ID: covidwho-1773987

ABSTRACT

The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases within the National Institutes of Health established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants that could potentially affect the transmission, virulence, and resistance to infection- and vaccine-induced immunity. The SAVE programme is a critical data-generating component of the US Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines and therapeutics, and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models and notable findings facilitated by this collaborative approach and identify future challenges. This programme is a template for the response to rapidly evolving pathogens with pandemic potential by monitoring viral evolution in the human population to identify variants that could reduce the effectiveness of countermeasures.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Biological Evolution , COVID-19 Vaccines , Humans , National Institute of Allergy and Infectious Diseases (U.S.) , Pandemics/prevention & control , Pharmacogenomic Variants , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , United States/epidemiology , Virulence
11.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331535

ABSTRACT

The PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2) cohort follows health care workers with and without documented coronavirus disease 2019 (COVID-19) since April 2020. We report our findings regarding SARS-CoV-2 spike binding antibody stability and protection from infection in the pre-variant era. We analyzed data from 400 healthcare workers (150 seropositive and 250 seronegative at enrollment) for a median of 84 days. The SARS-CoV-2 spike binding antibody titers were highly variable with antibody levels decreasing over the first three months, followed by a relative stabilization. We found that both more advanced age (>40 years) and female sex were associated with higher antibody levels (1.6-fold and 1.4-fold increases, respectively). Only six percent of the initially seropositive participants "seroreverted". We documented a total of 11 new SARS-CoV-2 infections (ten naive participants, one previously infected participant without detectable antibodies, p<0.01) indicating that spike antibodies limit the risk of re-infection. These observations, however, only apply to SARS-CoV-2 variants antigenically similar to the ancestral SARS-CoV-2 ones. In conclusion, SARS-CoV-2 antibody titers mounted upon infection are stable over several months in most people and provide protection from infection with antigenically similar viruses.

12.
Cell Rep ; 38(7): 110394, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1719436

ABSTRACT

The emergence of the SARS-CoV-2 Delta variant (B.1.617.2) raises concerns about potential reduced sensitivity of the virus to antibody neutralization and subsequent vaccine breakthrough infections. Here, we use a live virus neutralization assay with sera from Pfizer- and Moderna-vaccinated individuals to examine neutralizing antibody titers against SARS-CoV-2 and observe a 3.9- and 2.7-fold reduction, respectively, in neutralizing antibody titers against the Delta variant compared with an early isolate bearing only a D614G substitution in its spike protein. We observe similar reduced sensitivity with sera from hamsters that were previously infected with an early isolate of SARS-CoV-2. Despite this reduction in neutralizing antibody titers against the Delta variant, hamsters previously infected (up to 15 months earlier) with an early isolate are protected from infection with the Delta variant, suggesting that the immune response to the first infection is sufficient to provide protection against subsequent infection with the Delta variant.


Subject(s)
Adaptive Immunity , COVID-19/immunology , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/transmission , COVID-19/virology , COVID-19 Vaccines/immunology , Cricetinae , Disease Models, Animal , Humans , Reinfection/immunology , Reinfection/transmission , Reinfection/virology , SARS-CoV-2/genetics , Viral Load
13.
Clin Infect Dis ; 2021 Aug 19.
Article in English | MEDLINE | ID: covidwho-1703958

ABSTRACT

BACKGROUND: There are few data on the full spectrum of disease caused by SARS-CoV-2 infection across the lifespan from community-based or non-clinical settings. METHODS: We followed 2,338 people in Managua, Nicaragua, aged 0 to 94 years old from March 2020 through March 2021. SARS-CoV-2 infection was identified through real-time reverse transcription polymerase chain reaction (RT-PCR) or through enzyme-linked immunosorbent assay (ELISA). Disease presentation was assessed at the time of infection or retrospectively by survey at the time of blood collection. RESULTS: There was a large epidemic that peaked between March-August 2020. In total, 129 RT-PCR-positive infections were detected, for an overall incidence rate of 5.3 infections per 100 person-years (95% CI: 4.4-6.3). Seroprevalence was 56.7% (95%CI: 53.5%-60.1%) and was consistent from age 11 through adulthood but was lower in children aged ≤10 years. Overall, 31.0% of the infections were symptomatic, with 54.7% mild, 41.6% moderate, and 3.7% severe. There were two deaths that were likely due to SARS-CoV-2 infection, yielding an infection fatality rate of 0.2%. Antibody titers exhibited a J-shaped curve with respect to age, with the lowest titers observed among older children and young adults and the highest among older adults. When compared to SARS-CoV-2 seronegative individuals, SARS-CoV-2 seropositivity at the midyear sample was associated with 93.6% protection from symptomatic re-infection (95%CI: 51.1-99.2%). CONCLUSIONS: This population exhibited a very high SARS-CoV-2 seropositivity with lower-than-expected severity, and immunity from natural infection was protective against symptomatic re-infection.

14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322485

ABSTRACT

Background: Household transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) significantly contributes to increased community cases. Methods: We conducted a prospective case-ascertained study to investigate the household secondary attack rate (SAR) and contributing factors in urban Los Angeles, California, USA. Household members were enrolled prospectively if ≥1 member tested positive for SARS-CoV-2 by polymerase chain reaction (PCR). Nasopharyngeal swabs for PCR and symptom data were obtained over multiple longitudinal visits. Serology was obtained at enrollment. Findings: A total of 489 individuals in 105 households were enrolled from June to December 2020. The mean household SAR was 77.7% (95%CI: 71.4-84.0). A third (32.1%) of index cases were asymptomatic. High SAR was associated with both symptomatic and asymptomatic index cases (76.4% [95%CI: 68.8-83.9%] vs. 79.7% [95% CI: 66.2-93.3%], p=0.66). The most common age for index cases was children <18 years old during low community transmission periods and adults ≥18 years old during peak community transmission (p=0.003). Children and adults index cases both efficiently transmitted SARS-CoV-2 within households (SAR 74.0% [95%CI: 63.4-84.6%] vs. 81.3% [95%CI: 72.3-90.3%], p=0.49). Hispanic/Latinx ethnicity was significantly associated with higher SAR in the multivariable analysis of household factors (p= 0.030). Interpretation: The SAR in our urban setting with large ethnic minority populations is much higher than previously described. SAR was disproportionately and significantly impacted by Hispanic/Latinx ethnicity. Asymptomatic individuals and children play important roles as index cases. Future vaccination and public health efforts need special focus on these groups to help mitigate SARS-CoV-2 spread.Funding: NIH/NIAID U01AI144616-02S1, Open PhilanthropyDeclaration of Interests: PSP has received consultant fees from Sanofi-Pasteur and Seqirus. She also receives research funding from AstraZeneca for an unrelated study. AG has received consultant fees from Janssen. All other authors have no conflicts of interest to report.Ethics Approval Statement: The study was approved by the Institutional Review Board at Children’sHospital Los Angeles.

15.
Cell reports ; 2022.
Article in English | EuropePMC | ID: covidwho-1661117

ABSTRACT

As SARS-CoV-2 variants accumulate mutations, there is a risk of ineffective neutralizing antibodies against new variants and potential re-infection. Halfmann et al. report that, in the hamster model, previous infection with an early prototypical SARS-CoV-2 isolate prevents re-infection of the Delta variant and its transmission to naïve hamsters.

16.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296669

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 coronavirus infections from 2011-2016 with SARS-CoV-2 infections from March 2020-September 2021 in a Nicaraguan pediatric cohort. Respiratory samples were collected from participants that met testing criteria and blood samples were collected annually. Respiratory samples were tested for each of the endemic coronaviruses from 2011-2016 and for SARS-CoV-2 from 2020-2021 via rt-PCR. 2021 blood samples were tested for SARS-CoV-2 antibodies and a subset of 2011-2016 blood samples from four-years-old participants were tested for endemic coronavirus antibodies. By April 2021, 854 (49%) active 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 coronavirus 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 coronavirus 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.

17.
J Infect Dis ; 224(4): 643-647, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1545949

ABSTRACT

Influenza is associated with primary viral and secondary bacterial pneumonias; however, the dynamics of this relationship in populations with varied levels of pneumococcal vaccination remain unclear. We conducted nested matched case-control studies in 2 prospective cohorts of Nicaraguan children aged 2-14 years: 1 before pneumococcal conjugate vaccine introduction (2008-2010) and 1 following introduction and near universal adoption (2011-2018). The association between influenza and pneumonia was similar in both cohorts. Participants with influenza (across types/subtypes) had higher odds of developing pneumonia in the month following influenza infection. These findings underscore the importance of considering influenza in interventions to reduce global pneumonia burden.


Subject(s)
Influenza, Human , Pneumococcal Infections , Pneumococcal Vaccines/administration & dosage , Case-Control Studies , Child , Child, Preschool , Humans , Infant , Influenza, Human/epidemiology , Nicaragua , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumonia, Pneumococcal/epidemiology , Pneumonia, Pneumococcal/prevention & control , Prospective Studies , Vaccines, Conjugate
18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293022

ABSTRACT

Background: An immune correlate of protection from SARS-CoV-2 infection is urgently needed. Methods. We used an ongoing household cohort with an embedded transmission study that closely monitors participants regardless of symptom status. Real-time reverse-transcription polymerase chain reaction (RT-PCR) and Enzyme-linked immunosorbent assays (ELISAs) were used to measure infections and seropositivity. Sequencing was performed to determine circulating strains of SARS-CoV-2. We investigated the protection associated with seropositivity resulting from prior infection, the anti-spike antibody titers needed for protection, and we compared the severity of first and second infections. Results. In March 2021, 62.3% of the cohort was seropositive. After March 2021, gamma and delta variants predominated. Seropositivity was associated with 69.2% protection from any infection (95% CI: 60.7%-75.9%), with higher protection against moderate or severe infection (79.4%, 95% CI: 64.9%-87.9%). Anti-spike titers of 327 and 2,551 were associated with 50% and 80% protection from any infection;titers of 284 and 656 were sufficient for protection against moderate or severe disease. Second infections were less severe than first infections (Relative Risk (RR) of moderated or severe disease: 0.6, 95% CI: 0.38-0.98;RR of subclinical disease:1.9, 95% CI: 1.33-2.73). Conclusions. Prior infection-induced immunity is protective against infection when predominantly gamma and delta SARS-CoV-2 circulated. The protective antibody titers presented may be useful for vaccine policy and control measures. While second infections were somewhat less severe, they were not as mild as ideal. A strategy involving vaccination will be needed to ease the burden of the SARS-CoV-2 pandemic.

19.
Clin Infect Dis ; 2021 Aug 19.
Article in English | MEDLINE | ID: covidwho-1364785

ABSTRACT

BACKGROUND: There are few data on the full spectrum of disease caused by SARS-CoV-2 infection across the lifespan from community-based or non-clinical settings. METHODS: We followed 2,338 people in Managua, Nicaragua, aged 0 to 94 years old from March 2020 through March 2021. SARS-CoV-2 infection was identified through real-time reverse transcription polymerase chain reaction (RT-PCR) or through enzyme-linked immunosorbent assay (ELISA). Disease presentation was assessed at the time of infection or retrospectively by survey at the time of blood collection. RESULTS: There was a large epidemic that peaked between March-August 2020. In total, 129 RT-PCR-positive infections were detected, for an overall incidence rate of 5.3 infections per 100 person-years (95% CI: 4.4-6.3). Seroprevalence was 56.7% (95%CI: 53.5%-60.1%) and was consistent from age 11 through adulthood but was lower in children aged ≤10 years. Overall, 31.0% of the infections were symptomatic, with 54.7% mild, 41.6% moderate, and 3.7% severe. There were two deaths that were likely due to SARS-CoV-2 infection, yielding an infection fatality rate of 0.2%. Antibody titers exhibited a J-shaped curve with respect to age, with the lowest titers observed among older children and young adults and the highest among older adults. When compared to SARS-CoV-2 seronegative individuals, SARS-CoV-2 seropositivity at the midyear sample was associated with 93.6% protection from symptomatic re-infection (95%CI: 51.1-99.2%). CONCLUSIONS: This population exhibited a very high SARS-CoV-2 seropositivity with lower-than-expected severity, and immunity from natural infection was protective against symptomatic re-infection.

20.
Clin Infect Dis ; 72(10): e476-e483, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1232182

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused substantial morbidity and mortality worldwide. Few reports exist in Latin America, a current epicenter of transmission. Here, we aim to describe the epidemiology and outcomes associated with coronavirus disease 2019 (COVID-19) in Honduras. METHODS: Baseline clinical and epidemiological information of SARS-CoV-2 reverse transcriptase polymerase chain reaction-confirmed cases detected between 17 March-4 May in the San Pedro Sula Metropolitan area was collected; for hospitalized cases, clinical data were abstracted. Logistic regression models were fit to determine the factors associated with hospitalization. RESULTS: We identified 877 COVID-19 cases, of which 25% (n = 220) were hospitalized. The 19-44-year age group (57.8%) and males (61.3%) were predominant in overall COVID-19 cases. Of the cases, 34% (n = 299) had at least 1 preexisting medical condition. Individuals aged 45-69 years (adjusted odds ratio [aOR] = 4.05; 95% confidence interval [CI], 2.85-5.76) or ≥70 years (aOR = 9.12; 95% CI, 5.24-15.86), of male sex (aOR = 1.72; 95% CI, 1.21-2.44), and those with a preexisting condition (aOR = 2.12; 95% CI, 1.43-3.14) had higher odds of hospitalization. Of inpatients, 50% were hospitalized more than 7 days. The median length of hospitalization was 13 days (interquartile range [IQR], 8-29) among individuals aged 19-44 years, and 17 days (IQR, 11-24.6) among those aged 45-69. Of the fatal cases, 42% occurred among adults under 60 years old. CONCLUSIONS: Our findings show that a high proportion of COVID-19 cases in Honduras occurred among younger adults, who also constituted a significant proportion of severe and fatal cases. Preexisting conditions were associated with severe outcomes independently from age and were highly prevalent in Honduran COVID-19 cases.


Subject(s)
COVID-19 , Adult , Aged , Honduras/epidemiology , Hospitalization , Humans , Male , Middle Aged , Pandemics , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Young Adult
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