Evobiopsychosocial medicine.

The biopsychosocial model remains the de facto framework of current healthcare, but lacks causational depth, scientific rigour, or any recognition of the importance of evolutionary theory for understanding health and disease. In this article it is updated to integrate Tinbergen's four questions with the three biopsychosocial levels. This 'evobiopsychosocial' schema provides a more complete framework for understanding causation of medical conditions. Its application is exemplified by tabulating depression, rheumatoid arthritis and COVID-19 within its format, which highlights the direct research and practical applications uniquely offered by evolutionary medicine. An evobiopsychosocial framework can serve as a useful tool to introduce evolutionary concepts into mainstream medicine by highlighting the broad and specific contributions of evolutionary analysis to researching, treating and preventing health conditions, providing a suitable next step for the mainstream model of medicine.

The Effect of COVID-19 Vaccines on Stroke Outcomes: A Single-Center Study.

BACKGROUND: One of the defining narratives of the COVID-19 pandemic has been the acceptance and distribution of vaccine. To compare the outcomes of COVID-19 positive vaccinated and unvaccinated stroke patients. METHODS: This is a single-center retrospective study of COVID-19-vaccinated and unvaccinated stroke patients between April 2020 and March 2022. All patients presenting with stroke regardless of treatment modalities were included. National Institutes of Health Stroke Scale was used to assess stroke severity. The primary outcome was functional capacity of the patients at discharge. RESULTS: The study cohort comprised 203 COVID-19 positive stroke patients divided into 139 unvaccinated and 64 fully vaccinated patients. At discharge, the modified Rankin scale score was significantly lower in the vaccinated cohort (3[1-4] vs. 4[2-5], odds ratio = 0.508, P = 0.011). At 3 months of follow-up, the median modified Rankin scale score was comparable between both cohorts. CONCLUSIONS: Although vaccination did not show any significant difference in stroke patient outcomes on follow-up, vaccines were associated with lower rates of morbidity and mortality at discharge among stroke patients during the pandemic.

Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa.

Background: More than half the global population has been exposed to SARS-CoV-2. Naturally induced immunity influences the outcome of subsequent exposure to variants and vaccine responses. We measured anti-spike IgG responses to explore the basis for this enhanced immunity. Methods: A prospective cohort study of mothers in a South African community through ancestral/beta/delta/omicron SARS-CoV-2 waves (March 2020-February 2022). Health seeking behaviour/illness were recorded and post-wave serum samples probed for IgG to Spike (CoV2-S-IgG) by ECLISA. To estimate protective CoV2-S-IgG threshold levels, logistic functions were fit to describe the correlation of CoV2-S-IgG measured before a wave and the probability for seroconversion/boosting thereafter for unvaccinated and vaccinated adults. Findings: Despite little disease, 176/339 (51·9%) participants were seropositive following wave 1, rising to 74%, 89·8% and 97·3% after waves 2, 3 and 4 respectively. CoV2-S-IgG induced by natural exposure protected against subsequent SARS-CoV-2 infection with the greatest protection for beta and least for omicron. Vaccination induced higher CoV2-S-IgG in seropositive compared to naïve vaccinees. Amongst seropositive participants, proportions above the 50% protection against infection threshold were 69% (95% CrI: 62, 72) following 1 vaccine dose, 63% (95% CrI: 63, 75) following 2 doses and only 11% (95% CrI: 7, 14) in unvaccinated during the omicron wave. Interpretation: Naturally induced CoV2-S-IgG do not achieve high enough levels to prevent omicron infection in most exposed individuals but are substantially boosted by vaccination leading to significant protection. A single vaccination in those with prior immunity is more immunogenic than 2 doses in a naïve vaccinee and may provide adequate protection. Funding: UK NIH GECO award (GEC111), Wellcome Trust Centre for Infectious Disease Research in Africa (CIDRI), Bill & Melinda Gates Foundation, USA (OPP1017641, OPP1017579) and NIH H3 Africa (U54HG009824, U01AI110466]. HZ is supported by the SA-MRC. MPN is supported by an Australian National Health and Medical Research Council Investigator Grant (APP1174455). BJQ is supported by a grant from the Bill and Melinda Gates Foundation (OPP1139859). Stefan Flasche is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant number 208812/Z/17/Z).

High Neutralizing Antibody Levels Against Severe Acute Respiratory Syndrome Coronavirus 2 Omicron BA.1 and BA.2 After UB-612 Vaccine Booster.

The highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has caused high rates of breakthrough infections in those previously vaccinated with ancestral strain coronavirus disease 2019 (COVID-19) vaccines. Here, we demonstrate that a booster dose of UB-612 vaccine candidate delivered 7-9 months after primary vaccination increased neutralizing antibody levels by 131-, 61-, and 49-fold against ancestral SARS-CoV-2 and the Omicron BA.1 and BA.2 variants, respectively. Based on the receptor-binding domain protein binding antibody responses, the UB-612 third-dose booster may lead to an estimated approximately 95% efficacy against symptomatic COVID-19 caused by the ancestral strain. Our results support UB-612 as a potential potent booster against current and emerging SARS-CoV-2 variants.

Transmission dynamics of SARS-CoV-2 in a strictly-Orthodox Jewish community in the UK.

Some social settings such as households and workplaces, have been identified as high risk for SARS-CoV-2 transmission. Identifying and quantifying the importance of these settings is critical for designing interventions. A tightly-knit religious community in the UK experienced a very large COVID-19 epidemic in 2020, reaching 64.3% seroprevalence within 10 months, and we surveyed this community both for serological status and individual-level attendance at particular settings. Using these data, and a network model of people and places represented as a stochastic graph rewriting system, we estimated the relative contribution of transmission in households, schools and religious institutions to the epidemic, and the relative risk of infection in each of these settings. All congregate settings were important for transmission, with some such as primary schools and places of worship having a higher share of transmission than others. We found that the model needed a higher general-community transmission rate for women (3.3-fold), and lower susceptibility to infection in children to recreate the observed serological data. The precise share of transmission in each place was related to assumptions about the internal structure of those places. Identification of key settings of transmission can allow public health interventions to be targeted at these locations.

Towards a population-based threshold of protection for COVID-19 vaccines.

Correlates of protection for COVID-19 vaccines are urgently needed to license additional vaccines. We measured immune responses to four COVID-19 vaccines of proven efficacy using a single serological platform. IgG anti-Spike antibodies were highly correlated with ID50 neutralization in a validated pseudoviral assay and correlated significantly with efficacies for protection against infection with wild-type, alpha and delta variant SARS-CoV-2 virus. The protective threshold for each vaccine was calculated for IgG anti-Spike antibody. The mean protective threshold for all vaccine studies for WT virus was 154 BAU/ml (95 %CI 42-559), and for studies with antibody distributions that enabled precise estimation of thresholds (i.e. leaving out 2-dose mRNA regimens) was 60 BAU/ml (95 %CI 35-102). We propose that the proportion of individuals with responses above the appropriate protective threshold together with the geometric mean concentration can be used in comparative non-inferiority studies with licensed vaccines to ensure that new vaccines will be efficacious.

SARS-CoV-2 seroprevalence in a strictly-Orthodox Jewish community in the UK: A retrospective cohort study.

BACKGROUND: Ethnic and religious minorities have been disproportionately affected by SARS-CoV-2 worldwide. The UK strictly-Orthodox Jewish community has been severely affected by the pandemic. This group shares characteristics with other ethnic minorities including larger family sizes, higher rates of household crowding and relative socioeconomic deprivation. We studied a UK strictly-Orthodox Jewish population to understand transmission of COVID-19 within this community. METHODS: We performed a household-focused cross-sectional SARS-CoV-2 serosurvey between late-October and early December 2020 prior to the third national lockdown. Randomly-selected households completed a standardised questionnaire and underwent serological testing with a multiplex assay for SARS-CoV-2 IgG antibodies. We report clinical illness and testing before the serosurvey, seroprevalence stratified by age and sex. We used random-effects models to identify factors associated with infection and antibody titres. FINDINGS: A total of 343 households, consisting of 1,759 individuals, were recruited. Serum was available for 1,242 participants. The overall seroprevalence for SARS-CoV-2 was 64.3% (95% CI 61.6-67.0%). The lowest seroprevalence was 27.6% in children under 5 years and rose to 73.8% in secondary school children and 74% in adults. Antibody titres were higher in symptomatic individuals and declined over time since reported COVID-19 symptoms, with the decline more marked for nucleocapsid titres. INTERPRETATION: In this tight-knit religious minority population in the UK, we report one of the highest SARS-CoV-2 seroprevalence levels in the world to date, which was markedly higher than the reported 10% seroprevalence in London at the time of the study. In the context of this high force of infection, all age groups experienced a high burden of infection. Actions to reduce the burden of disease in this and other minority populations are urgently required. FUNDING: This work was jointly funded by UKRI and NIHR [COV0335; MR/V027956/1], a donation from the LSHTM Alumni COVID-19 response fund, HDR UK, the MRC and the Wellcome Trust.

COVID-19 sequelae in adults aged less than 50 years: A systematic review.

BACKGROUND: There is emerging evidence of long-term sequelae in a considerable proportion of COVID-19 patients after recovery and the spectrum and severity of such sequelae should be systematically reviewed. This review aims to evaluate the available evidence of all intermediate and long-term COVID-19 sequelae affecting formerly healthy adults. METHODS: A systematic literature search of Embase, WHO, Scopus, Pubmed, Litcovid, bioRxiv and medRxiv was conducted with a cutoff date of the 17th September 2020 according to PRISMA guidelines and registered in PROSPERO (CRD42020208725). Search terms included "COVID-19", "coronavirus disease 2019", "SARS-CoV-2", "sequelae" and "consequence*". Publications on adult participants, with a confirmed SARS-CoV-2 infection were included. Elderly (>50 years old) and children (<18 years old) were excluded. Bias assessment was performed using a modified Newcastle-Ottawa Scale. RESULTS: A total of 31 papers were included. Study types included prospective and retrospective cohort studies, cross-sectional studies and case reports. Sequelae persistence since infection spanned 14 days to three months. Sequelae included persistent fatigue (39-73% of assessed persons), breathlessness (39-74%), decrease in quality of life (44-69%), impaired pulmonary function, abnormal CT findings including pulmonary fibrosis (39-83%), evidence of peri-/perimyo-/myocarditis (3-26%), changes in microstructural and functional brain integrity with persistent neurological symptoms (55%), increased incidence of psychiatric diagnoses (5.8% versus 2.5-3.4% in controls), incomplete recovery of olfactory and gustatory dysfunction (33-36% of evaluated persons). CONCLUSIONS: A variety of organ systems are affected by COVID-19 in the intermediate and longer-term after recovery. Main sequelae include post-infectious fatigue, persistent reduced lung function and carditis. Careful follow-up post COVID 19 is indicated to assess and mitigate possible organ damage and preserve life quality.

Evaluation of a novel multiplexed assay for determining IgG levels and functional activity to SARS-CoV-2.

BACKGROUND: The emergence of SARS-CoV-2 has led to the development of serological assays that could aid in an understanding of the burden of COVID-19 disease. Many available tests lack rigorous evaluation and therefore results may be misleading. OBJECTIVES: The aim of this study was to assess the performance of a novel multiplexed immunoassay for the simultaneous detection of antibodies against SARS-CoV-2 trimeric spike (S), spike receptor binding domain (RBD), spike N terminal domain and nucleocapsid antigen and a novel pseudo-neutralisation assay. METHODS: A multiplexed solid-phase chemiluminescence assay (Meso Scale Discovery) was evaluated for the simultaneous detection of IgG binding to four SARS-CoV-2 antigens and the quantification of antibody-induced ACE-2 binding inhibition (pseudo-neutralisation assay). Sensitivity was evaluated with a total of 196 COVID-19 serum samples (169 confirmed PCR positive and 27 anti-nucleocapsid IgG positive) from individuals with mild symptomatic or asymptomatic disease. Specificity was evaluated with 194 control serum samples collected from adults prior to December 2019. RESULTS: The specificity and sensitivity of the binding IgG assay was highest for S protein with a specificity of 97.4 % and sensitivity of 96.2 % for samples taken 14 days and 97.9 % for samples taken 21 days following the onset of symptoms. IgG concentration to S and RBD correlated strongly with percentage inhibition measured by the pseudo-neutralisation assay. CONCLUSION: Excellent sensitivity for IgG detection was obtained over 14 days since onset of symptoms for three SARS-CoV-2 antigens (S, RBD and N) in this multiplexed assay which can also measure antibody functionality.