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1.
Age Ageing ; 53(9)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39317334

RESUMEN

The UK is launching a new free vaccination programme against respiratory syncytial virus (RSV) in adults aged 75 or over. This follows the development of safe and effective vaccines against RSV and the growing realisation of the burden of RSV-related disease in older adults-estimated at circa 8000 deaths and 175 000 GP episodes every year in the UK. It is likely that the full burden of RSV-related illness is under-appreciated and under-reported due to a lack of testing and awareness of its dangers in older adults. Healthcare professionals working with older people should be aware of the evidence base and be in a position to advise patients on the risks and benefits of vaccination and nonvaccination. We briefly review the evidence for the safety and effectiveness of the two licensed vaccines against RSV with a special focus on what geriatricians and others working with frailer, older people need to know.


Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Anciano , Anciano de 80 o más Años , Humanos , Factores de Edad , Geriatras , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/epidemiología , Vacunas contra Virus Sincitial Respiratorio/administración & dosificación , Reino Unido/epidemiología , Vacunación/estadística & datos numéricos
2.
Open Forum Infect Dis ; 11(8): ofae418, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39113828

RESUMEN

Background: We characterized the global epidemiology and seasonality of human coronaviruses (HCoVs) OC43, NL63, 229E, and HKU1. Methods: In this systematic review, we searched MEDLINE, EMBASE, Web of Science, SCOPUS, CINAHL, and backward citations for studies published until 1 September 2023. We included studies with ≥12 months of consecutive data and tested for ≥1 HCoV species. Case reports, review articles, animal studies, studies focusing on SARS-CoV-1, SARS-CoV-2, and/or Middle East respiratory syndrome, and those including <100 cases were excluded. Study quality and risk of bias were assessed using Joanna Briggs Institute Critical Appraisal Checklist tools. We reported the prevalence of all HCoVs and individual species. Seasonality was reported for studies that included ≥100 HCoVs annually. This study is registered with PROSPERO, CRD42022330902. Results: A total of 201 studies (1 819 320 samples) from 68 countries were included. A high proportion were from China (19.4%; n = 39), whereas the Southern Hemisphere was underrepresented. Most were case series (77.1%, n = 155) with samples from secondary care (74.1%, n = 149). Seventeen (8.5%) studies included asymptomatic controls, whereas 76 (37.8%) reported results for all 4 HCoV species. Overall, OC43 was the most prevalent HCoV. Median test positivity of OC43 and NL63 was higher in children, and 229E and HKU1 in adults. Among 18 studies that described seasonality (17 from the Northern Hemisphere), circulation of all HCoVs mostly peaked during cold months. Conclusions: In our comprehensive review, few studies reported the prevalence of individual HCoVs or seasonality. Further research on the burden and circulation of HCoVs is needed, particularly from Africa, South Asia, and Central/South America.

4.
Nat Immunol ; 25(4): 607-621, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38589621

RESUMEN

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.


Asunto(s)
Investigación Biomédica , COVID-19 , Humanos , Síndrome Post Agudo de COVID-19 , Hospitalización , Inmunoglobulina G
5.
Commun Med (Lond) ; 4(1): 32, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38418616

RESUMEN

BACKGROUND: The associations between deprivation and illness trajectory after hospitalisation for coronavirus disease-19 (COVID-19) are uncertain. METHODS: A prospective, multicentre cohort study was conducted on post-COVID-19 patients, enrolled either in-hospital or shortly post-discharge. Two evaluations were carried out: an initial assessment and a follow-up at 28-60 days post-discharge. The study encompassed research blood tests, patient-reported outcome measures, and multisystem imaging (including chest computed tomography (CT) with pulmonary and coronary angiography, cardiovascular and renal magnetic resonance imaging). Primary and secondary outcomes were analysed in relation to socioeconomic status, using the Scottish Index of Multiple Deprivation (SIMD). The EQ-5D-5L, Brief Illness Perception Questionnaire (BIPQ), Patient Health Questionnaire-4 (PHQ-4) for Anxiety and Depression, and the Duke Activity Status Index (DASI) were used to assess health status. RESULTS: Of the 252 enrolled patients (mean age 55.0 ± 12.0 years; 40% female; 23% with diabetes), deprivation status was linked with increased BMI and diabetes prevalence. 186 (74%) returned for the follow-up. Within this group, findings indicated associations between deprivation and lung abnormalities (p = 0.0085), coronary artery disease (p = 0.0128), and renal inflammation (p = 0.0421). Furthermore, patients with higher deprivation exhibited worse scores in health-related quality of life (EQ-5D-5L, p = 0.0084), illness perception (BIPQ, p = 0.0004), anxiety and depression levels (PHQ-4, p = 0.0038), and diminished physical activity (DASI, p = 0.002). At the 3-month mark, those with greater deprivation showed a higher frequency of referrals to secondary care due to ongoing COVID-19 symptoms (p = 0.0438). However, clinical outcomes were not influenced by deprivation. CONCLUSIONS: In a post-hospital COVID-19 population, socioeconomic deprivation was associated with impaired health status and secondary care episodes. Deprivation influences illness trajectory after COVID-19.


In our study, we aimed to understand how socioeconomic factors impact recovery from COVID-19 following hospitalisation. We followed 252 patients, collecting health data and utilising advanced imaging techniques. We discovered that individuals from deprived areas experienced more severe health complications, reported worse quality of life, and required more specialist care. However, their clinical outcomes were not significantly different. This underscores that socioeconomic deprivation affects health recovery, underlining the need for tailored care for these individuals. Our findings emphasise the importance of considering socioeconomic factors in recovery plans post-COVID-19, potentially improving healthcare for those in deprived areas.

6.
Open Forum Infect Dis ; 11(2): ofad643, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38312213

RESUMEN

Background: We investigated endemic respiratory virus circulation patterns in Malawi, where no lockdown was imposed, during the COVID-19 pandemic. Methods: Within a prospective household cohort in urban and rural Malawi, adult participants provided upper respiratory tract (URT) samples at 4 time points between February 2021 and April 2022. Polymerase chain reaction (PCR) was performed for SARS-CoV-2, influenza, and other endemic respiratory viruses. Results: 1626 URT samples from 945 participants in 542 households were included. Overall, 7.6% (n = 123) samples were PCR- positive for >1 respiratory virus; SARS-CoV-2 (4.4%) and rhinovirus (2.0%) were most common. No influenza A virus was detected. Influenza B and respiratory syncytial virus (RSV) were rare. Higher virus positivity were detected in the rural setting and at earlier time points. Coinfections were infrequent. Conclusions: Endemic respiratory viruses circulated in the community in Malawi during the pandemic, though influenza and RSV were rarely detected. Distinct differences in virus positivity and demographics were observed between urban and rural cohorts.

7.
J Infect Dis ; 230(2): e363-e373, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-38365443

RESUMEN

BACKGROUND: The aim of this study was to characterize the epidemiology of human seasonal coronaviruses (HCoVs) in southern Malawi. METHODS: We tested for HCoVs 229E, OC43, NL63, and HKU1 using real-time polymerase chain reaction (PCR) on upper respiratory specimens from asymptomatic controls and individuals of all ages recruited through severe acute respiratory illness (SARI) surveillance at Queen Elizabeth Central Hospital, Blantyre, and a prospective influenza-like illness (ILI) observational study between 2011 and 2017. We modeled the probability of having a positive PCR for each HCoV using negative binomial models, and calculated pathogen-attributable fractions (PAFs). RESULTS: Overall, 8.8% (539/6107) of specimens were positive for ≥1 HCoV. OC43 was the most frequently detected HCoV (3.1% [191/6107]). NL63 was more frequently detected in ILI patients (adjusted incidence rate ratio [aIRR], 9.60 [95% confidence interval {CI}, 3.25-28.30]), while 229E (aIRR, 8.99 [95% CI, 1.81-44.70]) was more frequent in SARI patients than asymptomatic controls. In adults, 229E and OC43 were associated with SARI (PAF, 86.5% and 89.4%, respectively), while NL63 was associated with ILI (PAF, 85.1%). The prevalence of HCoVs was similar between children with SARI and controls. All HCoVs had bimodal peaks but distinct seasonality. CONCLUSIONS: OC43 was the most prevalent HCoV in acute respiratory illness of all ages. Individual HCoVs had distinct seasonality that differed from temperate settings.


Asunto(s)
Infecciones por Coronavirus , Coronavirus , Estaciones del Año , Humanos , Malaui/epidemiología , Masculino , Adulto , Preescolar , Femenino , Niño , Adolescente , Lactante , Persona de Mediana Edad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Adulto Joven , Coronavirus/genética , Coronavirus/aislamiento & purificación , Estudios Prospectivos , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Anciano , Recién Nacido
9.
Sci Rep ; 13(1): 15014, 2023 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-37697014

RESUMEN

The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Control de Enfermedades Transmisibles , Anticuerpos Neutralizantes , Transporte Biológico
10.
Front Immunol ; 14: 1146702, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37056776

RESUMEN

The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.


Asunto(s)
COVID-19 , Masculino , Humanos , Femenino , Anciano , SARS-CoV-2 , Estudios Prospectivos , Formación de Anticuerpos , ARN Viral , Anticuerpos Antivirales , Proteínas de la Nucleocápside , Hospitales , Gravedad del Paciente , Inmunoglobulina M
11.
Nature ; 617(7961): 555-563, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36996873

RESUMEN

An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.


Asunto(s)
Infecciones por Adenovirus Humanos , Dependovirus , Hepatitis , Niño , Humanos , Enfermedad Aguda/epidemiología , Infecciones por Adenovirus Humanos/epidemiología , Infecciones por Adenovirus Humanos/genética , Infecciones por Adenovirus Humanos/virología , Alelos , Estudios de Casos y Controles , Linfocitos T CD4-Positivos/inmunología , Coinfección/epidemiología , Coinfección/virología , Dependovirus/aislamiento & purificación , Predisposición Genética a la Enfermedad , Virus Helper/aislamiento & purificación , Hepatitis/epidemiología , Hepatitis/genética , Hepatitis/virología , Hepatocitos/virología , Cadenas HLA-DRB1/genética , Cadenas HLA-DRB1/inmunología , Hígado/virología
12.
Open Heart ; 10(1)2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36822817

RESUMEN

BACKGROUND: We investigated the associations of healthcare worker status with multisystem illness trajectory in hospitalised post-COVID-19 individuals. METHODS AND RESULTS: One hundred and sixty-eight patients were evaluated 28-60 days after the last episode of hospital care. Thirty-six (21%) were healthcare workers. Compared with non-healthcare workers, healthcare workers were of similar age (51.3 (8.7) years vs 55.0 (12.4) years; p=0.09) more often women (26 (72%) vs 48 (38%); p<0.01) and had lower 10-year cardiovascular risk (%) (8.1 (7.9) vs 15.0 (11.5); p<0.01) and Coronavirus Clinical Characterisation Consortium in-hospital mortality risk (7.3 (10.2) vs 12.7 (9.8); p<0.01). Healthcare worker status associated with less acute inflammation (peak C reactive protein 48 mg/L (IQR: 14-165) vs 112 mg/L (52-181)), milder illness reflected by WHO clinical severity score distribution (p=0.04) and shorter duration of admission (4 days (IQR: 2-6) vs 6 days (3-12)).In adjusted multivariate logistic regression analysis, healthcare worker status associated with a binary classification (probable/very likely vs not present/unlikely) of adjudicated myocarditis (OR: 2.99; 95% CI (1.01 to 8.89) by 28-60 days postdischarge).After a mean (SD, range) duration of follow-up after hospital discharge of 450 (88) days (range 290, 627 days), fewer healthcare workers died or were rehospitalised (1 (3%) vs 22 (17%); p=0.038) and secondary care referrals for post-COVID-19 syndrome were common (42%) and similar to non-healthcare workers (38%; p=0.934). CONCLUSION: Healthcare worker status was independently associated with the likelihood of adjudicated myocarditis, despite better antecedent health. Two in five healthcare workers had a secondary care referral for post-COVID-19 syndrome. TRIAL REGISTRATION NUMBER: NCT04403607.


Asunto(s)
COVID-19 , Miocarditis , Femenino , Humanos , Persona de Mediana Edad , Cuidados Posteriores , COVID-19/complicaciones , COVID-19/diagnóstico , Miocarditis/diagnóstico , Miocarditis/epidemiología , Alta del Paciente , Síndrome Post Agudo de COVID-19 , SARS-CoV-2 , Personal de Salud , Masculino , Adulto , Anciano
13.
Int J Epidemiol ; 52(2): 355-376, 2023 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-36850054

RESUMEN

BACKGROUND: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. METHODS: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). RESULTS: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. CONCLUSIONS: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.


Asunto(s)
COVID-19 , Humanos , Masculino , Niño , Persona de Mediana Edad , COVID-19/terapia , SARS-CoV-2 , Unidades de Cuidados Intensivos , Modelos de Riesgos Proporcionales , Factores de Riesgo , Hospitalización
14.
PLoS Med ; 20(1): e1004086, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36719907

RESUMEN

BACKGROUND: Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic. METHODS AND FINDINGS: We included patients > = 19 years with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. We defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, and comorbidities. We used Bayesian logistic regression to explore mortality over time. Between 17 January 2020 and 28 February 2022, we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. In total, 29% (n = 6,499) of immunocompromised and 21% (n = 28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjusted OR 1.44, 95% CI [1.39, 1.50], p < 0.001). Not all immunocompromising conditions had the same risk, for example, patients on active cancer treatment were less likely to have their care escalated to intensive care (adjusted OR 0.77, 95% CI [0.7, 0.85], p < 0.001) or ventilation (adjusted OR 0.65, 95% CI [0.56, 0.76], p < 0.001). However, cancer patients were more likely to die (adjusted OR 2.0, 95% CI [1.87, 2.15], p < 0.001). Analyses were adjusted for age, sex, socioeconomic deprivation, comorbidities, and vaccination status. As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age: the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50 to 69 years was 88% for men and 83% for women, and for those >80 years was 99% for men and 98% for women. The study is limited by a lack of detailed drug data prior to admission, including steroid doses, meaning that we may have incorrectly categorised some immunocompromised patients as immunocompetent. CONCLUSIONS: Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses, monoclonal antibodies, and nonpharmaceutical preventive interventions should be continually encouraged for this patient group. TRIAL REGISTRATION: ISRCTN 66726260.


Asunto(s)
COVID-19 , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , SARS-CoV-2 , Estudios Prospectivos , Mortalidad Hospitalaria , Teorema de Bayes , Huésped Inmunocomprometido , Reino Unido/epidemiología , Organización Mundial de la Salud
15.
EClinicalMedicine ; 56: 101800, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36600885

RESUMEN

Background: The B.1.1.529 (Omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the fourth COVID-19 pandemic wave across the southern African region, including Malawi. The seroprevalence of SARS-CoV-2 antibodies and their association with epidemiological trends of hospitalisations and deaths are needed to aid locally relevant public health policy decisions. Methods: We conducted a population-based serosurvey from December 27, 2021 to January 17, 2022, in 7 districts across Malawi to determine the seroprevalence of SARS-CoV-2 antibodies. Serum samples were tested for antibodies against SARS-CoV-2 receptor binding domain using WANTAI SARS-CoV-2 Receptor Binding Domain total antibody commercial enzyme-linked immunosorbent assay (ELISA). We also evaluated COVID-19 epidemiologic trends in Malawi, including cases, hospitalisations and deaths from April 1, 2021 through April 30, 2022, collected using the routine national COVID-19 reporting system. A multivariable logistic regression model was developed to investigate the factors associated with SARS-CoV-2 seropositivity. Findings: Serum samples were analysed from 4619 participants (57% female; 60% aged 18-50 years), of whom 878/3794 (23%) of vaccine eligible adults had received a single dose of any COVID-19 vaccine. The overall assay-adjusted seroprevalence was 83.7% (95% confidence interval (CI), 79.3%-93.4%). Seroprevalence was lowest among children <13 years of age (66%) and highest among adults 18-50 years of age (82%). Seroprevalence was higher among vaccinated compared to unvaccinated participants (1 dose, 94% vs. 77%, adjusted odds ratio 4.89 [95% CI, 3.43-7.22]; 2 doses, 97% vs. 77%, aOR 6.62 [95% CI, 4.14-11.3]). Urban residents were more likely to be seropositive than those from rural settings (91% vs. 78%, aOR 2.76 [95% CI, 2.16-3.55]). There was at least a two-fold reduction in the proportion of hospitalisations and deaths among the reported cases in the fourth wave compared to the third wave (hospitalisations, 10.7% (95% CI, 10.2-11.3) vs. 4.86% (95% CI, 4.52-5.23), p < 0.0001; deaths, 3.48% (95% CI, 3.18-3.81) vs. 1.15% (95% CI, 1.00-1.34), p < 0.0001). Interpretation: We report reduction in proportion of hospitalisations and deaths from SARS-CoV-2 infections during the Omicron variant dominated wave in Malawi, in the context of high SARS-CoV-2 seroprevalence and low COVID-19 vaccination coverage. These findings suggest that COVID-19 vaccination policy in high seroprevalence settings may need to be amended from mass campaigns to targeted vaccination of reported at-risk populations. Funding: Supported by the Bill and Melinda Gates Foundation (INV-039481).

16.
EBioMedicine ; 87: 104402, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36543718

RESUMEN

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript.


Asunto(s)
COVID-19 , SARS-CoV-2 , Adulto , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19 , Estudios de Seguimiento , Vacunación , Hospitalización , Inmunoglobulina A , Inmunoglobulina G , Anticuerpos Antivirales , Anticuerpos Neutralizantes
17.
Int J Infect Dis ; 137: 118-125, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38465577

RESUMEN

OBJECTIVES: This study aimed to investigate the changing SARS-CoV-2 seroprevalence and associated health and sociodemographic factors in Malawi between February 2021 and April 2022. METHODS: In total, four 3-monthly serosurveys were conducted within a longitudinal population-based cohort in rural Karonga District and urban Lilongwe, testing for SARS-CoV-2 S1 immunoglobulin (Ig)G antibodies using an enzyme-linked immunosorbent assay. Population seroprevalence was estimated in all and unvaccinated participants. Bayesian mixed-effects logistic models estimated the odds of seropositivity in the first survey, and of seroconversion between surveys, adjusting for age, sex, occupation, location, and assay sensitivity/specificity. RESULTS: Of the 2005 participants (Karonga, n = 1005; Lilongwe, n = 1000), 55.8% were female and median age was 22.7 years. Between Surveys (SVY) 1 and 4, population-weighted SARS-CoV-2 seroprevalence increased from 26.3% to 89.2% and 46.4% to 93.9% in Karonga and Lilongwe, respectively. At SVY4, seroprevalence did not differ by COVID-19 vaccination status in adults, except for those aged 30+ years in Karonga (unvaccinated: 87.4%, 95% credible interval 79.3-93.0%; two doses: 98.1%, 94.8-99.5%). Location and age were associated with seroconversion risk. Individuals with hybrid immunity had higher SARS-CoV-2 seropositivity and antibody titers, than those infected. CONCLUSION: High SARS-CoV-2 seroprevalence combined with low morbidity and mortality indicate that universal vaccination is unnecessary at this stage of the pandemic, supporting change in national policy to target at-risk groups.


Asunto(s)
COVID-19 , Adulto , Humanos , Femenino , Adulto Joven , Masculino , Teorema de Bayes , COVID-19/epidemiología , Vacunas contra la COVID-19 , Estudios de Cohortes , Malaui/epidemiología , SARS-CoV-2 , Estudios Seroepidemiológicos , Anticuerpos Antivirales
18.
Open Forum Infect Dis ; 9(11): ofac531, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36381618

RESUMEN

Background: We conducted this study to assess the prevalence of viral coinfection in a well characterized cohort of hospitalized coronavirus disease 2019 (COVID-19) patients and to investigate the impact of coinfection on disease severity. Methods: Multiplex real-time polymerase chain reaction testing for endemic respiratory viruses was performed on upper respiratory tract samples from 1002 patients with COVID-19, aged <1 year to 102 years old, recruited to the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK study. Comprehensive demographic, clinical, and outcome data were collected prospectively up to 28 days post discharge. Results: A coinfecting virus was detected in 20 (2.0%) participants. Multivariable analysis revealed no significant risk factors for coinfection, although this may be due to rarity of coinfection. Likewise, ordinal logistic regression analysis did not demonstrate a significant association between coinfection and increased disease severity. Conclusions: Viral coinfection was rare among hospitalized COVID-19 patients in the United Kingdom during the first 18 months of the pandemic. With unbiased prospective sampling, we found no evidence of an association between viral coinfection and disease severity. Public health interventions disrupted normal seasonal transmission of respiratory viruses; relaxation of these measures mean it will be important to monitor the prevalence and impact of respiratory viral coinfections going forward.

19.
Lancet Respir Med ; 10(11): 1011-1013, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36228636
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