ABSTRACT
Population-based study is known to be a very essential type of study during and after a pandemic or epidemics, as it provides important information on the incidence, prevalence and risk factors of the disease in question. There has been limited information about challenges faced in conducting such surveys in Nigeria. In this paper, we would share our experience, and describe the challenges faced in conducting population-based seroepidemiological study of COVID – 19 in Lagos, Nigeria. Some challenges were peculiar to specific Local Government Areas (LGAs) while others were general. The challenges include general misconception of community members about health research, difficulties in mapping houses, planning for data collection, standardising data collection, working in hard-to-reach community when resources were limited as well as difficulty in collection of blood, oral and naso-oropharyngeal swabs. Ways of overcoming these problems, lessons learnt, and recommendations are hereby discussed.
Subject(s)
COVID-19ABSTRACT
ABSTRACT Affordable novel strategies are needed to treat COVID-19 cases complicated by respiratory compromise in resource limited settings. We report a mixed-methods pre-post assessment of 1) the useability of CPAP/O2 helmet non-invasive ventilation (NIV) to treat COVID-19, at ∼ 1% the cost of mechanical ventilation; 2) the effectiveness of a train-the-trainer practice facilitation intervention; and 3) whether use of CPAP/O2 helmet NIV was associated with increased COVID-19 infection among healthcare workers. At baseline, eight COVID-19 treatment centers in Nigeria (CircumVent network) received CPAP/O2 helmet systems, and were instructed on its use. After five months, clinicians within the CircumVent netwok participated in a 2-day train-the-trainers educational intervention. The physicians completed i) standardized forms on patient demographics, clinical course, and outcomes for patients seen in the treatment centers; ii) standardized surveys of feasibility and acceptability of use of CPAP/O2 helmet systems; and iii) in-depth-interviews to explore facilitators and barriers to implementation of CPAP/O2 helmet NIV. Physicians described the CPAP/O2 helmet ventilator as easy to use and they felt comfortable training their staff on its use. They rated CPAP/O2 helmet NIV as feasible, acceptable, and appropriate (mean score of 4.0, 3.8, and 3.9 out of 5, respectively, on standardized scales). Case report forms for 546 patients with suspected and/or confirmed COVID-19 infection were obtained between May 2020 and November 2021. Of these, 69% (n=376) were treated before the training; and 29.7% (n=162) were treated with CPAP/O2 helmet ventilation. CPAP/O2 helmet NIV was well-tolerated by patients, with 12% reporting claustrophobia, and 2% reporting loose- or tight-fitting helmets. Although patient outcomes improved among CPAP/O2 helmet users overall, this was not associated with training (P=0.2). This finding persisted after adjustment for disease severity at presentation. Serosurvey of 282 health workers across treatment centers revealed that 40% (n=112) were seropositive for SARS-CoV-2. Seropositivity was significantly associated with direct contact with COVID-19 patients and limited access to PPE and hand hygiene during aerosol generating procedures (P = 0.02), but not use of CPAP/O2 helmet (P’s ≥ 0.2). In conclusion, physicians effectively used CPAP/O2 helmet NIV systems to treat COVID-19 patients in Nigeria without need for practice facilliation of their training and without increased risk of infection among healthcare workers. The use of CPAP/O2 helmet NIV could be an important strategy for treating individuals with COVID-19 infection and other disease conditions complicated by respiratory distress, particularly in settings were resources such mechanical ventilation are limited.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
There is a paucity of real-world data on vaccine elicited neutralising antibody responses for AZD1222, in African populations following vaccination scale up. Here, we first measured baseline SARS-CoV-2 seroprevalence and levels of protective neutralizing antibodies prior to vaccination rollout using both flow cytometric based analysis of binding antibodies coupled with pseudotyped virus neutralisation assays in two study cohorts from West Africa: Nigerian healthcare workers; (n = 140) and a Ghanaian general community cohort (n = 527). We found that 44% and 28% of pre-vaccination participants showed IgG anti-N positivity, increasing to 59% and 42% respectively with anti-receptor binding dominan (RBD) IgG specific antibodies. The increased prevalence of prior exposure using anti RBD antibodies was corroborated by Pseudotyped virus (PV) neutralizing antibody assays, indicating that overall, 50% of prior infections were missed by N antibody testing. PV titres (serum dilution required to inhibit 50% of infection, ID50) against wild type following 2-dose vaccination regimen were [145 (4.5) to 2579 (4.2) vs 57 (3.0) to 1049 (6.7)] (GMT ± s.d), delta [75 (3.0) to 549 (3.7) vs 37 (2.4) to 453 (7.4)] (GMT ± s.d) and omicron variants [37 (2.4) to 453 (7.4) vs 29 (1.8) to 95 (5.3)] (GMT ± s.d) in the Nigerian (1 month) vs Ghanaian participants (2 months) post vaccination (total n = 94). Previous IgG anti-N was associated with significantly higher neutralizing antibody levels with an observed 3.5-fold [1423 (3.9) vs 4674 (3.4)] (GMT ± s.d) and 2.7-fold [779 (7.1) vs 2128 (4.8) (GMT ± s.d) difference between N positive and negative participants in the Nigerian and Ghanaian cohorts respectively. We also observed serological evidence from N, S and RBD antibodies of breakthrough infection in 8/49 (16%) of Nigerian vaccinees over only 2 months, with neutralisation profiles suggesting delta variant infection consistent with the sampling period when this variant was known to dominate. Importantly, neutralising antibodies waned at 3 months after second dose vs 1 month post second-dose 1695 (4.3)] vs 2579 (4.2) in the Nigerian population who were N negative throughout. IgG anti-N was also observed to wane below cut-off in a total 19/94 (20%) of subjects highlighting the need for a combination of additional markers to characterise previous infection. We conclude that AZD1222 is immunogenic in two independent real world West African cohorts with high background seroprevalence and incidence of breakthrough infection in 2021. Waning titres at 6 months post second dose indicates the need for booster dosing after AZD1222 in the African setting despite hybrid immunity from previous infection.
ABSTRACT
Background Access to vaccines has contributed to the control of COVID-19. However, evaluation of the effectiveness of the vaccines in a setting where the vaccines were not originally tested is critically important. This study evaluates the clinical and laboratory characteristics of COVID-19 vaccine breakthrough infections among healthcare workers (HCWs). Methods A multicentre prospective study among HCWs who had two doses of the Oxford/AstraZeneca ChAdOx1-S [recombinant] (AZD1222) vaccine were followed up 24 weeks. Nasopharyngeal and oropharyngeal specimens were tested using RT-PCR for SARS-CoV-2 and positive samples were subjected to whole genome sequencing for variant assignment. Result A total of 369 HCWs were enrolled; of which 24 (6.5%) had breakthrough infections. There was equal sex distribution among the breakthrough cases. The majority were aged between 30 to 39years (37.5%), and had mild symptoms of cough, fever, headache, and nausea/vomiting (58%), with no hospitalization. Among the 24 breakthrough cases whose whole genomes were successfully sequenced, three were confirmed to be Delta B.1.617.2 variant during the 3 rd wave and an additional three were confirmed as omicron B.1.1.529 variant during the 4 th wave. Conclusion We reported vaccine breakthrough cases among fully vaccinated HCWs with the majority presenting with mild illness. Both delta and omicron variants were identified during the different epidemiologic spectrums of SARS-CoV-2. Therefore, there is a need to scale up vaccination for all front-line health workers and high-risk populations in developing countries.
Subject(s)
COVID-19 , FeverABSTRACT
Background: There are no data on vaccine elicited neutralising antibody responses for the most widely used vaccine, AZD1222, in African populations following scale up. Here, we measured i. baseline SARS-CoV-2 seroprevalence and levels of protective antibodies prior to vaccination rollout using both flow cytometric based analysis of binding antibodies to nucleocapsid (N), coupled with virus neutralisation approaches and ii. neutralizing antibody responses to VOC prior to vaccination (January 2021) and after two-doses of AZD1222 vaccine administered between June and July 2021 in Lagos, Nigeria, during a period when the Delta variant was also circulating. Methods: Health workers at multiple sites in Lagos were recruited to the study. For binding antibody measurement, IgG antibodies against SARS-COV-2 Wuhan-1 receptor-binding domain (RBD), trimeric spike protein (S), nucleocapsid protein (N) and Omicron S1 were measured using the Luminex-based SARS-CoV-2-IgG assay by flow cytometry. For plasma neutralising antibody measurement, SARS-CoV-2 lentiviral pseudovirus (PV) were prepared by transfecting 293T cells with Wuhan-614G wild type (WT), B.1.617.2 (Delta) and BA.1 (Omicron) plasmids in conjunction with HIV-1 expression vectors and luciferase encoding genome flanked by LTRs. We performed serial plasma dilutions from each time point and mixed plasma with PV before infecting HeLa-ACE2 cell lines, reading out luminescence and calculating ID50 (dilution of sera required to inhibit 50% of PV infection). Results: Our study population who received at least one dose of vaccine comprised 140 participants with a median age of 40 (interquartile range: 33, 48). 62/140 (44%) participants were anti-N IgG positive prior to administration of first vaccine dose. 49 had plasma samples available at baseline prior to vaccination and at two follow-up timepoints post vaccination for neutralization assays. Half of the participants, 25/49 (51%) were IgG anti-N positive at baseline. Of the 24 individuals anti-N Ab negative at baseline, 12/24 had ID50 above the cut-off of 20. In these individuals, binding antibodies to S were also detectable, and neutralisation correlated with IgG anti-S. Overall, neutralizing Ab titres to WT 1 month after second dose were 2579 and at 3 months post second-dose were 1695. As expected, lower levels of neutralization were observed against the Delta GMT 549 and Omicron variants 269 at 1 month. Positive anti-N IgG Ab status at baseline was associated with significantly higher titres of neutralizing antibodies following vaccination across all tested VOC. Those with anti-N Abs present at baseline did not experience waning of responses between months 1 and 3 post second dose. When data were analysed for negative anti-N IgG status at any timepoint, there was a significant decline in neutralization and binding antibodies between 1 month and 3 months post second-dose. The GMT in these individuals for Delta and Omicron was approximately 100, nearly a log lower in comparison to WT. We tested anti-N IgG in subjects who were anti-N IgG negative at baseline (n=78) and became positive between 1- and 3-months post second dose and found 7/49 (14%) with de-novo infection, with one additional participant demonstrating both reinfection and breakthrough infection to yield a total breakthrough rate of 8/49 (16%). Neutralising and binding Ab titres 1 month post vaccine, prior to breakthrough, did not appear to be associated with breakthrough infection. Neutralizing titres were higher at the last time point in individuals who had experienced vaccine breakthrough infection (with no evidence of infection prior to vaccine), indicating a boosting effect of infection in addition to vaccine. We noted that the increase in titres against Delta PV observed in breakthrough was significantly greater than the increase for WT and Omicron PVs, coincident with in the Delta wave of infection during the sampling period. Conclusions: AZD1222 is immunogenic in this real world west African cohort with significant background seroprevalence and incidence of breakthrough infection over a short time period. Prior infection and breakthrough infection induced higher anti-SARS-CoV-2 Ab responses at 3 months post vaccine against all widely circulating VOC. However, responses to Omicron BA.1 were reduced at three months regardless of prior exposure. Given that data suggesting that mRNA vaccine booster third doses induce broader, more potent responses with reduced mortality in the elderly, further doses after AZD1222 should be considered for those at high risk.
Subject(s)
Breakthrough PainABSTRACT
Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) exhibits a high mutations rate and monitoring its spread and evolution is essential for global control of the pandemic. This study determined the SARS-CoV-2 variants circulating in Lagos, from July 2021 to January 2022, when the nation experienced its third and fourth waves.The study utilised archived SARS-CoV-2 positive samples and Midnight whole-genome sequencing workflow from Oxford Nanopore Technologies. Six hundred and sixty-six archived SARS-CoV-2 positive samples, 488 community testing and 178 travellers were analysed. Three hundred forty-one sequences samples were assigned lineages, but 327 sequences with doubly verified collection dates recreated the timeline. 86.5% of the samples came from persons between 16 and 60 years old. Two infections with the Omicron variant (BA.1) among community testers were detected in August 2021 and from seven outbound travellers in September 2021. An inbound traveller also had the Omicron variant (BA.1) in September 2021. Thirteen lineages of the Delta variant and four lineages of the Omicron variant were detected.We show that the Omicron variant was in Nigeria before November 2021 and could have caused the short reprieve between the third and fourth waves. Several lineages detected suggest several introductions, highlighting the need for surveillance.