Estimating pneumococcal carriage dynamics in adults living with HIV in a mature infant pneumococcal conjugate vaccine programme in Malawi, a modelling study.

BACKGROUND: Adults living with human immunodeficiency virus (ALWHIV) receiving antiretroviral therapy (ART) exhibit higher pneumococcal carriage prevalence than adults without HIV (HIV-). To assess factors influencing high pneumococcal carriage in ALWHIV, we estimated pneumococcal carriage acquisition and clearance rates in a high transmission and disease-burdened setting at least 10 years after introducing infant PCV13 in routine immunisation. METHODS: We collected longitudinal nasopharyngeal swabs from individuals aged 18-45 in Blantyre, Malawi. The study group included both HIV- individuals and those living with HIV, categorised based on ART duration as either exceeding 1 year (ART > 1y) or less than 3 months (ART < 3 m). Samples were collected at baseline and then weekly for 16 visits. To detect pneumococcal carriage, we used classical culture microbiology, and to determine pneumococcal serotypes, we used latex agglutination. We modelled trajectories of serotype colonisation using multi-state Markov models to capture pneumococcal carriage dynamics, adjusting for age, sex, number of under 5 year old (< 5y) children, social economic status (SES), and seasonality. RESULTS: We enrolled 195 adults, 65 adults in each of the study groups. 51.8% were females, 25.6% lived with more than one child under 5 years old, and 41.6% lived in low socioeconomic areas. The median age was 33 years (IQR 25-37 years). The baseline pneumococcal carriage prevalence of all serotypes was 31.3%, with non-PCV13 serotypes (NVT) at 26.2% and PCV13 serotypes (VT) at 5.1%. In a multivariate longitudinal analysis, pneumococcal carriage acquisition was higher in females than males (hazard ratio [HR], NVT [1.53]; VT [1.96]). It was also higher in low than high SES (NVT [1.38]; VT [2.06]), in adults living with 2 + than 1 child < 5y (VT [1.78]), and in ALWHIV on ART > 1y than HIV- adults (NVT [1.43]). Moreover, ALWHIV on ART > 1y cleared pneumococci slower than HIV- adults ([0.65]). Residual VT 19F and 3 were highly acquired, although NVT remained dominant. CONCLUSIONS: The disproportionately high point prevalence of pneumococcal carriage in ALWHIV on ART > 1y is likely due to impaired nasopharyngeal clearance, which results in prolonged carriage. Our findings provide baseline estimates for comparing pneumococcal carriage dynamics after implementing new PCV strategies in ALWHIV.

Longevity of hybrid immunity against SARS-CoV-2 in adults vaccinated with an adenovirus-based COVID-19 vaccine.

BACKGROUND: Hybrid immunity provides better protection against COVID-19 than vaccination or prior natural infection alone. It induces high magnitude and broadly cross-reactive neutralising anti-Spike IgG antibodies. However, it is not clear how long these potent antibodies last, especially in the context of adenovirus-based COVID-19 vaccines. METHODS: We conducted a longitudinal cohort study and enrolled 20 adults who had received an adenovirus-based COVID-19 vaccine before a laboratory-confirmed SARS-CoV-2 infection. We followed up the study participants for 390 days post the initial breakthrough infection. We assessed the longevity and cross-reactive breadth of serum antibodies against SARS-CoV-2 variants of concern (VOCs), including Omicron. RESULTS: The binding anti-Spike IgG antibodies remained within the reported putative levels for at least 360 days and were cross-neutralising against Beta, Gamma, Delta, and Omicron. During the follow up period, a median of one SARS-CoV-2 re-infection event was observed across the cohort, but none resulted in severe COVID-19. Moreover, the re-exposure events were associated with augmented anti-Spike and anti-RBD IgG antibody titres. CONCLUSIONS: This study confirms that hybrid immunity provides durable broadly cross-reactive antibody immunity against SARS-CoV-2 variants of concern for at least a year (360 days), and that it is further augment by SARS-CoV-2 re-exposure.

AstraZeneca COVID-19 vaccine induces robust broadly cross-reactive antibody responses in Malawian adults previously infected with SARS-CoV-2.

BACKGROUND: Binding and neutralising anti-Spike antibodies play a key role in immune defence against SARS-CoV-2 infection. Since it is known that antibodies wane with time and new immune-evasive variants are emerging, we aimed to assess the dynamics of anti-Spike antibodies in an African adult population with prior SARS-CoV-2 infection and to determine the effect of subsequent COVID-19 vaccination. METHODS: Using a prospective cohort design, we recruited adults with prior laboratory-confirmed mild/moderate COVID-19 in Blantyre, Malawi, and followed them up for 270 days (n = 52). A subset of whom subsequently received a single dose of the AstraZeneca COVID-19 vaccine (ChAdOx nCov-19) (n = 12). We measured the serum concentrations of anti-Spike and receptor-binding domain (RBD) IgG antibodies using a Luminex-based assay. Anti-RBD antibody cross-reactivity across SARS-CoV-2 variants of concern (VOC) was measured using a haemagglutination test. A pseudovirus neutralisation assay was used to measure neutralisation titres across VOCs. Ordinary or repeated measures one-way ANOVA was used to compare log10 transformed data, with p value adjusted for multiple comparison using Sídák's or Holm-Sídák's test. RESULTS: We show that neutralising antibodies wane within 6 months post mild/moderate SARS-CoV-2 infection (30-60 days vs. 210-270 days; Log ID50 6.8 vs. 5.3, p = 0.0093). High levels of binding anti-Spike or anti-RBD antibodies in convalescent serum were associated with potent neutralisation activity against the homologous infecting strain (p < 0.0001). A single dose of the AstraZeneca COVID-19 vaccine following mild/moderate SARS-CoV-2 infection induced a 2 to 3-fold increase in anti-Spike and -RBD IgG levels 30 days post-vaccination (both, p < 0.0001). The anti-RBD IgG antibodies from these vaccinated individuals were broadly cross-reactive against multiple VOCs and had neutralisation potency against original D614G, beta, and delta variants. CONCLUSIONS: These findings show that the AstraZeneca COVID-19 vaccine is an effective booster for waning cross-variant antibody immunity after initial priming with SARS-CoV-2 infection. The potency of hybrid immunity and its potential to maximise the benefits of COVID-19 vaccines needs to be taken into consideration when formulating vaccination policies in sub-Saharan Africa, where there is still limited access to vaccine doses.

High SARS-CoV-2 seroprevalence in health care workers but relatively low numbers of deaths in urban Malawi.

BACKGROUND: In low-income countries, like Malawi, important public health measures including social distancing or a lockdown have been challenging to implement owing to socioeconomic constraints, leading to predictions that the COVID-19 pandemic would progress rapidly. However, due to limited capacity to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, there are no reliable estimates of the true burden of infection and death. We, therefore, conducted a SARS-CoV-2 serosurvey amongst health care workers (HCWs) in Blantyre city to estimate the cumulative incidence of SARS-CoV-2 infection in urban Malawi. METHODS: We recruited 500 otherwise asymptomatic HCWs from Blantyre City (Malawi) from 22nd May 2020 to 19th June 2020 and serum samples were collected from all participants. A commercial ELISA was used to measure SARS-CoV-2 IgG antibodies in serum. RESULTS: A total of 84 participants tested positive for SARS-CoV-2 antibodies. The HCWs with positive SARS-CoV-2 antibody results came from different parts of the city. The adjusted seroprevalence of SARS-CoV-2 antibodies was 12.3% [CI 8.2 - 16.5]. Using age-stratified infection fatality estimates reported from elsewhere, we found that at the observed adjusted seroprevalence, the number of predicted deaths was eight times the number of reported deaths. CONCLUSIONS: The high seroprevalence of SARS-CoV-2 antibodies among HCWs and the discrepancy in the predicted versus reported deaths suggests that there was early exposure but slow progression of COVID-19 epidemic in urban Malawi. This highlights the urgent need for development of locally parameterised mathematical models to more accurately predict the trajectory of the epidemic in sub-Saharan Africa for better evidence-based policy decisions and public health response planning.