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Immunoglobulin gene heterogeneity reflects the diversity and focus of the humoral immune response towards different infections, enabling inference of B cell development processes. Detailed compositional and lineage analysis of long read IGH repertoire sequencing, combining examples of pandemic, epidemic and endemic viral infections with control and vaccination samples, demonstrates general responses including increased use of IGHV4-39 in both Zaire Ebolavirus (EBOV) and COVID-19 patient cohorts. We also show unique characteristics absent in Respiratory Syncytial Virus or yellow fever vaccine samples: EBOV survivors show unprecedented high levels of class switching events while COVID-19 repertoires from acute disease appear underdeveloped. Despite the high levels of clonal expansion in COVID-19 IgG1 repertoires there is a striking lack of evidence of germinal centre mutation and selection. Given the differences in COVID-19 morbidity and mortality with age, it is also pertinent that we find significant differences in repertoire characteristics between young and old patients. Our data supports the hypothesis that a primary viral challenge can result in a strong but immature humoral response where failures in selection of the repertoire risk off-target effects. [ABSTRACT FROM AUTHOR]

We describe a case series of 35 Ebola virus disease (EVD) survivors during the epidemic in West Africa who had neurologic and accompanying psychiatric sequelae. Survivors meeting neurologic criteria were invited from a cohort of 361 EVD survivors to attend a preliminary clinic. Those whose severe neurologic features were documented in the preliminary clinic were referred for specialist neurologic evaluation, ophthalmologic examination, and psychiatric assessment. Of 35 survivors with neurologic sequelae, 13 had migraine headache, 2 stroke, 2 peripheral sensory neuropathy, and 2 peripheral nerve lesions. Of brain computed tomography scans of 17 patients, 3 showed cerebral and/or cerebellar atrophy and 2 confirmed strokes. Sixteen patients required mental health followup; psychiatric disorders were diagnosed in 5. The 10 patients who experienced greatest disability had co-existing physical and mental health conditions. EVD survivors may have ongoing central and peripheral nervous system disorders, including previously unrecognized migraine headaches and stroke. [ABSTRACT FROM AUTHOR]

Background: Passive therapy with convalescent plasma provides an early opportunity to intervene in Ebola virus disease (EVD). Methods for field screening and selection of potential donors and quantifying plasma antibody are needed.Study Design and Methods: Recombinant Ebola virus glycoprotein (EBOV GP) was formatted into immunoglobulin G-capture, competitive, and double-antigen bridging enzyme immunoassays (EIAs). EVD survivors in Freetown, Sierra Leone, were recruited as potential plasma donors and assessed locally using sera alone and/or paired sera and oral fluids (ORFs). Uninfected controls comprised unexposed Gambians and communities in Western Area, Sierra Leone. Antibody neutralization in selected sera was measured retrospectively in a pseudotype virus assay.Results: A total of 115 potential donors were considered for enrollment: 110 plasma samples were concordantly reactive in the three EIAs; three were concordantly unreactive and two were reactive in two of three EIAs (98.2% agreement; 95% confidence interval [CI], 93.9%-99.8%). In 88 donors with paired ORF and plasma, G-capture EIA reactivity correlated well in the two analytes (R2  = 0.795). Plasma and ORF from 44 Gambians were unreactive. ORF samples from 338 of 339 unexposed Western Area community controls were unreactive (specificity, 99.7%; 95% CI, 98.4%-99.7%); ORF samples from 113 of 116 Kerry Town EVD survivors were reactive (sensitivity, 97.4%; 95% CI, 92.5%-99.5%). Strong reactivity in G-capture and/or competitive EIAs identified donors with high plasma EBOV GP antibody levels in the double-antigen bridging assay, correlating with high levels of neutralizing antibody.Conclusions: In-field testing can qualify convalescent donors for providing high-titer antibody. [ABSTRACT FROM AUTHOR]

We conducted a case-control study in Freetown, Sierra Leone, to investigate ocular signs in Ebola virus disease (EVD) survivors. A total of 82 EVD survivors with ocular symptoms and 105 controls from asymptomatic civilian and military personnel and symptomatic eye clinic attendees underwent ophthalmic examination, including widefield retinal imaging. Snellen visual acuity was <6/7.5 in 75.6% (97.5% CI 63%-85.7%) of EVD survivors and 75.5% (97.5% CI 59.1%-87.9%) of controls. Unilateral white cataracts were present in 7.4% (97.5% CI 2.4%-16.7%) of EVD survivors and no controls. Aqueous humor from 2 EVD survivors with cataract but no anterior chamber inflammation were PCR-negative for Zaire Ebola virus, permitting cataract surgery. A novel retinal lesion following the anatomic distribution of the optic nerve axons occurred in 14.6% (97.5% CI 7.1%-25.6%) of EVD survivors and no controls, suggesting neuronal transmission as a route of ocular entry. [ABSTRACT FROM AUTHOR]

Thousands of persons have survived Ebola virus disease. Almost all survivors describe symptoms that persist or develop after hospital discharge. A cross-sectional survey of the symptoms of all survivors from the Ebola treatment unit (ETU) at 34th Regimental Military Hospital, Freetown, Sierra Leone (MH34), was conducted after discharge at their initial follow-up appointment within 3 weeks after their second negative PCR result. From its opening on December 1, 2014, through March 31, 2015, the MH34 ETU treated 84 persons (8-70 years of age) with PCR-confirmed Ebola virus disease, of whom 44 survived. Survivors reported musculoskeletal pain (70%), headache (48%), and ocular problems (14%). Those who reported headache had had lower admission cycle threshold Ebola PCR than did those who did not (p<0.03). This complete survivor cohort from 1 ETU enables analysis of the proportion of symptoms of post-Ebola syndrome. The Ebola epidemic is waning, but the effects of the disease will remain. [ABSTRACT FROM AUTHOR]

Ebola survivors (21/27 [77.8%]) suffered more disability than their close contacts (6/54 [11.1%]) (adjusted odds ratio, 23.5 [95% confidence interval, 6.5-85.7]; P < .001) when measured by the Washington Group Disability Extended Questionnaire. Major limitations in vision, mobility, cognition, and affect were observed in survivors 1 year following the 2014-2016 Ebola outbreak, highlighting the need for long-term rehabilitation. [ABSTRACT FROM AUTHOR]

Background: The frequency of asymptomatic infection with Ebola virus is unclear: previous estimates vary and there is no standard test. Asymptomatic infection with Ebola virus could contribute to population immunity, reducing spread. If people with asymptomatic infection are infectious it could explain re-emergences of Ebola virus disease (EVD) without known contact.Methods: We validated a new oral fluid anti-glycoprotein IgG capture assay among survivors from Kerry Town Ebola Treatment Centre and controls from communities unaffected by EVD in Sierra Leone. We then assessed the seroprevalence of antibodies to Ebola virus in a cross-sectional study of household contacts of the survivors. All household members were interviewed. Two reactive tests were required for a positive result, with a third test to resolve any discrepancies.Findings: The assay had a specificity of 100% (95% CI 98·9-100; 339 of 339 controls tested negative) and sensitivity of 95·9% (89·8-98·9; 93 of 97 PCR-confirmed survivors tested positive). Of household contacts not diagnosed with EVD, 47·6% (229 of 481) had high level exposure (direct contact with a corpse, body fluids, or a case with diarrhoea, vomiting, or bleeding). Among the contacts, 12·0% (95% CI 6·1-20·4; 11 of 92) with symptoms at the time other household members had EVD, and 2·6% (1·2-4·7; 10 of 388) with no symptoms tested positive. Among asymptomatic contacts, seropositivity was weakly correlated with exposure level.Interpretation: This new highly specific and sensitive assay showed asymptomatic infection with Ebola virus was uncommon despite high exposure. The low prevalence suggests asymptomatic infection contributes little to herd immunity in Ebola, and even if infectious, would account for few transmissions.Funding: Wellcome Trust ERAES Programme, Save the Children. [ABSTRACT FROM AUTHOR]