SARS-CoV-2 and Dengue Coinfection in Filipino Children: Epidemiology Profile, Clinical Presentation and Outcomes.

BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in dengue-endemic regions has raised concern on the possibility of coinfection, especially in children who bear the highest burden of illness. This study determined the incidence and described the profile of Filipino children with SARS-CoV-2 and dengue coinfection, and compared disease severity and outcome in children with coinfection to a matched group of children with SARS-CoV-2 monoinfection. METHODS: This was a retrospective matched cohort study of pediatric patients 0-18 years old diagnosed with SARS-CoV-2 and dengue coinfection or SARS-CoV-2 monoinfection in the Philippines and reported to the Surveillance and Analysis of Coronavirus disease 2019 (COVID-19) in Children Nationwide registry from March 01, 2020 to June 30, 2022. RESULTS: A total of 3,341 SARS-CoV-2 infections in children were reported. The SARS-CoV-2 and dengue coinfection incidence is 4.34% (n = 145). We matched 120 coinfections to monoinfections according to age, gender and timing of infection. More coinfection cases were classified as mild or moderate COVID-19, whereas more asymptomatic cases were seen in those with monoinfection. Rates were similar for severe and critical COVID-19 in both groups. Coinfections predominantly presented with typical dengue symptoms rather than COVID-19 symptoms and laboratory parameters. No differences in outcomes were observed between coinfection and monoinfection. The case fatality rates are 6.7% for coinfection and 5.0% for monoinfection. CONCLUSIONS: One in every 25 SARS-CoV-2 infections had a dengue coinfection. Continued surveillance is needed to establish the interaction of SARS-CoV-2 and dengue virus, evaluate the impact of COVID-19 and/or dengue vaccination on coinfection and monitor complications of coinfection.

The Hidden Impact of the COVID-19 Pandemic on Routine Childhood Immunization Coverage in Cameroon.

Background: The third round of the global pulse survey demonstrated that the abrupt and rapid progression of the COVID-19 pandemic significantly disrupted childhood immunization in many countries. Although Cameroon has reported over 120,000 COVID-19 cases, the reported national childhood vaccination coverage during the pandemic seems to have increased compared to that during the pre-COVID-19 period. Indeed, the first dose of the diphtheria, tetanus, and pertussis-containing vaccine (DTP-1) coverage increased from 85.4% in 2019 to 87.7% in 2020, and DTP-3 coverage increased from 79.5% in 2019 to 81.2% in 2020. The paucity of literature on the impact of COVID-19 on childhood vaccination in COVID-19 hotspot regions poses a challenge in developing a context-specific immunization recovery plan, hence the need to conduct this study. Methodology: We conducted a cross-sectional study using 2019 (pre-pandemic period) and 2020 (pandemic period) district childhood immunization data from the DHIS-2 database, weighted using completeness for each data entry against regional data completeness in 2020. Based on COVID-19 incidence, two hotspot regions were selected, with all districts (56/56) included in the final analysis. The Chi-square test was used to compare DTP-1 and DTP-3 coverage during the pre-pandemic and pandemic periods. Results: In the two hotspot regions, 8247 children missed DTP-1, and 12,896 children did not receive DTP-3 vaccines in the pandemic period compared to the results from the pre-pandemic period. Indeed, there was a significant drop in DTP-1 and DTP-3 coverage of 0.8% (p = 0.0002) and 3.1% (p = 0.0003), respectively, in the Littoral Region. Moreover, the Centre Region reported a 5.7% (p < 0.0001) and 7.6% (p < 0.0001) drop in DTP-1 and DTP-3 coverage, respectively. Most districts in the hotspot regions reported a decline in childhood immunization access (62.5%) and utilization (71.4%). Indeed, in the Littoral Region, 46% (11/24) and 58% (14/24) of districts experienced decreased vaccination access and utilization, respectively. Meanwhile, 75% (24/32) and 81% (26/32) of districts in the Centre Region experienced a drop in vaccination access and utilization, respectively. Conclusion: This study reported a situation where the national immunization indicators mask the impact of COVID-19 on childhood immunization in heavily hit regions. Therefore, this study presents valuable information for ensuring continuous vaccination service delivery during public health emergencies. The findings could also contribute to developing an immunization recovery plan and informing policy on future pandemic preparedness and response.

The need and challenges for development of vaccines against emerging infectious diseases.

OBJECTIVE: To identify and describe learnings from past pandemics and to suggest a framework for vaccine development as part of epi/pandemic readiness. SOURCE OF DATA: Articles/ reviews/letters on pandemic preparedness/ vaccines published between 2005 and 2022 in PubMed, MEDLINE, MedRxiv, BioRxiv, Research Square, Gates Open Research; who.int, cepi.net, visualcapitalist.com, airfinity.com, ted.com websites; press releases. SUMMARY OF FINDINGS: Disease pandemics caused by emerging pathogens impacted the social development, health and wealth of most societies in human history. In an outbreak, the first months determine its course. To block an exponential spread and the development of an epi/ pandemic early, vaccine availability in sufficient quantities is of paramount importance. It is inevitable that new human viruses will emerge. Any future pandemic will come likely from RNA viruses through zoonotic or vector transmission, but we cannot predict when or where "Disease X" will strike. Public health, scientific and societal readiness plans need to include: continuous identification of new viruses in common mammalian reservoir hosts; continuous epidemiological surveillance, including wastewater sampling; establishment of prototype vaccine libraries against various virus families sharing functional and structural properties; testing of various and innovative vaccine platforms including mRNA, vector, nasal or oral vaccines for suitability by virus family; functional clinical trial sites and laboratory networks in various geographies; more efficient phasing of preclinical and clinical activities; global harmonization and streamlining of regulatory requirements including pre-established protocols; and societal preparedness including combating any pandemic of misinformation. CONCLUSIONS: "Outbreaks are unavoidable, pandemics are optional".

Lessons from the pandemic: Responding to emerging zoonotic viral diseases-a Keystone Symposia report.

The COVID-19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10-13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium "Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases" to discuss the successes and challenges of the COVID-19 pandemic and what lessons can be applied moving forward. Speakers focused on experiences not only from the COVID-19 pandemic but also from outbreaks of other pathogens, including the Ebola virus, Lassa virus, and Nipah virus. A general consensus was that investments made during the COVID-19 pandemic in infrastructure, collaborations, laboratory and manufacturing capacity, diagnostics, clinical trial networks, and regulatory enhancements-notably, in low-to-middle income countries-must be maintained and strengthened to enable quick, concerted responses to future threats, especially to zoonotic pathogens.

Homologous and heterologous boosting of the ChAdOx1-S1-S COVID-19 vaccine with the SCB-2019 vaccine candidate: a randomized, controlled, phase 2 study

Background Ongoing outbreaks of COVID-19 are driven by waning immunity following primary immunizations and emergence of new SARS-CoV-2 variants which escape vaccine-induced neutralizing antibodies. It has been suggested that heterologous boosters could enhance and potentially maintain population immunity. Methods We assessed immunogenicity and reactogenicity of booster doses of different formulations of aluminium hydroxide-adjuvanted SCB-2019 vaccine (9 μg SCB-2019 with or without CpG-1018 adjuvant, or 30 μg SCB-2019 with CpG-1018) in Brazilian adults primed with ChAdOx1-S vector vaccine. S-protein antibodies and ACE2-binding inhibition were measured by ELISA on Days 1, 15 and 29. Participants self-reported solicited adverse events and reactions. Results All SCB-2019 formulations increased S-protein ELISA antibodies and ACE2 binding inhibition to a greater extent than ChAdOx1-S. After 30 μg SCB-2019 + CpG + aluminium hydroxide titers against wild-type S-protein were significantly higher than after ChAdOx1-S on Days 15 and 29, as were titers of neutralizing antibodies against wild-type strain and Beta, Gamma, Delta, and Omicron variants. Boosting with SCB-2019 or ChAdOx1-S was well tolerated with no vaccine-related serious or severe adverse events. Conclusions Boosting ChAdOx1-S-primed adults with SCB-2019 induced higher levels of antibodies against a wild-type strain and SARS-CoV-2 variants than a homologous ChAdOx1-S booster, highest responses being with the 30 μg SCB-2019 + CpG + aluminium hydroxide formulation.

Safety of the Fiocruz ChAdOx COVID-19 vaccine used in a mass vaccination campaign in Botucatu, Brazil.

INTRODUCTION: Brazil has been at the core of the COVID-19 pandemic, with the second-highest death toll worldwide. A mass vaccination campaign was initiated on May 16th, 2021, in Botucatu, Brazil, where two doses of ChadOx1-nCoV19 were offered 12 weeks apart to all 18-60- year-olds. This context offers a unique opportunity to study the vaccine safety during a mass campaign. METHODS: The first and second doses of the vaccine were administered in May and August 2021, respectively. Emergency room (ER) and hospitalization records were obtained from the Hospital das Clínicas da Faculdade de Medicina de Botucatu for six weeks before and six weeks after the first and second doses, from 4 April to 19 September 2021. Diagnoses with COVID-19-related ICD codes were excluded to distinguish any trends resulting from the COVID-19 pandemic. ER and hospital visits during the two time periods were compared, including an ICD code comparison, to identify any changes in disease distributions. Data were scanned for a defined list of Adverse Events of Special Interest (AESIs), as presented by the Safety Platform for Emergency Vaccines. RESULTS AND DISCUSSION: A total of 77,683 and 74,051 subjects received dose 1 and dose 2 of ChadOx1-nCoV19, respectively. Vaccination was well tolerated and not associated with any major safety concerns. Increases in ER visits 1 week following both doses were primarily seen in ICD codes related to non-serious side effects of the vaccine, including vaccination site pain and other local events. The neurological AESIs identified (2 of 3 cases of multiple sclerosis) were relapses of a pre-existing condition. One potentially serious hospitalization event for Bell's palsy had onset before vaccination with dose 1, in a patient who also had a viral infection of the central nervous system. There was no myocarditis, pericarditis cases, or vaccine-related increases in thromboembolic events.

Impact of previous exposure to SARS-CoV-2 and of S-Trimer (SCB-2019) COVID-19 vaccination on the risk of reinfection: a randomised, double-blinded, placebo-controlled, phase 2 and 3 trial.

BACKGROUND: We previously reported the efficacy of the adjuvanted-protein COVID-19 vaccine candidate S-Trimer (SCB-2019) in adults who showed no evidence of previous exposure to SARS-CoV-2. In this study, we aimed to investigate the extent of protection afforded by previous exposure to SARS-CoV-2 on subsequent COVID-19 infection, as well as the efficacy, safety, and reactogenicity of SCB-2019 in participants who were enrolled in the Study evaluating Protective-Efficacy and safety of Clover's Trimeric Recombinant protein-based and Adjuvanted COVID-19 vaccine (SPECTRA) trial who had already been exposed to SARS-CoV-2 before vaccination. METHODS: In a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial (SPECTRA) done at 31 sites in five countries, participants were randomly assigned 1:1 using the Cenduit Interactive Response Technology system (IQVIA, Durham, NC, USA), with a block size of six, to receive two doses of either SCB-2019 or placebo 21 days apart. The primary outcomes of the SPECTRA trial were vaccine efficacy, measured by real-time PCR (rtPCR)-confirmed COVID-19 of any severity, with onset from 14 days after the second vaccine dose, as well as the safety and solicited local and systemic adverse events in the phase 2 subset. Here, we present secondary analyses to calculate the protective efficacy due to previous exposure to SARS-CoV-2 against reinfection with COVID-19 according to severity in SPECTRA participants who had evidence of exposure to SARS-CoV-2 at baseline, including efficacy against identified viral variants, as well as efficacy of SCB-2019 vaccination in this population. FINDINGS: We enrolled 30 174 participants between March 24, 2021, and Aug 10, 2021. In the 14 670 participants who were randomly assigned to receive placebo, there were 418 (2·8%) confirmed cases of COVID-19; 65 (0·9%) of 7339 SARS-CoV-2-exposed participants, and 353 (4·8%) of 7331 SARS-CoV-2-naive participants (attack rates of 5·5 cases per 100 person-years for SARS-CoV-2-exposed participants and 32·4 cases per 100 person-years for SARS-CoV-2-naive participants). Protective efficacy due to previous exposure to SARS-CoV-2 was 83·2% (95% CI 78·0-87·3) against any COVID-19, 92·5% (82·9-97·3) against moderate-to-severe COVID-19, and 100% (59·3-100) against severe COVID-19; no SARS-CoV-2-exposed participants had hospitalisation associated with COVID-19. Protective efficacy against variants were 100% for alpha (B.1.1.7) and lambda (C.37) variants, 88·6% (14·9-99·7) for B.1.623, 93·6% (80·1-98·7) for gamma (P.1), and 92·4% (81·2-97·6) for mu (B.1.621) variants, and lowest against beta (B.1.351; 72·2% [33·1-89·9]) and delta (B.1.617.2; 77·2% [61·3-87·2]) variants. In addition, one dose of SCB-2019 had 49·9% (1·5-75·6) efficacy against any symptomatic COVID-19, and two doses had 64·2% (26·5-83·8) efficacy. SCB-2019 was well tolerated in SARS-CoV-2-exposed participants, but was associated with higher rates of injection site pain (89 [33·8%] of 263 participants) than placebo (16 [6·7%] of 239 participants). Rates of solicited systemic adverse events, severe adverse events, and serious adverse events were similar between vaccine and placebo groups, and with rates in SARS-CoV-2-naive vaccine recipients. INTERPRETATION: Previous exposure to SARS-CoV-2 decreased the risk and severity of subsequent COVID-19 infection, even against newly emerging variants. Protection is further enhanced by one or two doses of SCB-2019. FUNDING: Clover Biopharmaceuticals, The Coalition for Epidemic Preparedness Innovations (CEPI).

Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019. METHODS: This ongoing phase 2 and 3 double-blind, placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition, at 31 sites in five countries (Belgium, Brazil, Colombia, Philippines, and South Africa). The participants were randomly assigned 1:1 using a centralised internet randomisation system to receive two 0·5 mL intramuscular doses of SCB-2019 (30 µg, adjuvanted with 1·50 mg CpG-1018 and 0·75 mg alum) or placebo (0·9% sodium chloride for injection supplied in 10 mL ampoules) 21 days apart. All study staff and participants were masked, but vaccine administrators were not. Primary endpoints were vaccine efficacy, measured by RT-PCR-confirmed COVID-19 of any severity with onset from 14 days after the second dose in baseline SARS-CoV-2 seronegative participants (the per-protocol population), and the safety and solicited local and systemic adverse events in the phase 2 subset. This study is registered on EudraCT (2020-004272-17) and ClinicalTrials.gov (NCT04672395). FINDINGS: 30 174 participants were enrolled from March 24, 2021, until the cutoff date of Aug 10, 2021, of whom 30 128 received their first assigned vaccine (n=15 064) or a placebo injection (n=15 064). The per-protocol population consisted of 12 355 baseline SARS-CoV-2-naive participants (6251 vaccinees and 6104 placebo recipients). Most exclusions (13 389 [44·4%]) were because of seropositivity at baseline. There were 207 confirmed per-protocol cases of COVID-19 at 14 days after the second dose, 52 vaccinees versus 155 placebo recipients, and an overall vaccine efficacy against any severity COVID-19 of 67·2% (95·72% CI 54·3-76·8), 83·7% (97·86% CI 55·9-95·4) against moderate-to-severe COVID-19, and 100% (97·86% CI 25·3-100·0) against severe COVID-19. All COVID-19 cases were due to virus variants; vaccine efficacy against any severity COVID-19 due to the three predominant variants was 78·7% (95% CI 57·3-90·4) for delta, 91·8% (44·9-99·8) for gamma, and 58·6% (13·3-81·5) for mu. No safety issues emerged in the follow-up period for the efficacy analysis (median of 82 days [IQR 63-103]). The vaccine elicited higher rates of mainly mild-to-moderate injection site pain than the placebo after the first (35·7% [287 of 803] vs 10·3% [81 of 786]) and second (26·9% [189 of 702] vs 7·4% [52 of 699]) doses, but the rates of other solicited local and systemic adverse events were similar between the groups. INTERPRETATION: Two doses of SCB-2019 vaccine plus CpG and alum provides notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 viruses, including the predominating delta variant. FUNDING: Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations.

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil.

Several COVID-19 vaccines have shown good efficacy in clinical trials, but there remains uncertainty about the efficacy of vaccines against different variants. Here, we investigate the efficacy of ChAdOx1 nCoV-19 (AZD1222) against symptomatic COVID-19 in a post-hoc exploratory analysis of a Phase 3 randomised trial in Brazil (trial registration ISRCTN89951424). Nose and throat swabs were tested by PCR in symptomatic participants. Sequencing and genotyping of swabs were performed to determine the lineages of SARS-CoV-2 circulating during the study. Protection against any symptomatic COVID-19 caused by the Zeta (P.2) variant was assessed in 153 cases with vaccine efficacy (VE) of 69% (95% CI 55, 78). 49 cases of B.1.1.28 occurred and VE was 73% (46, 86). The Gamma (P.1) variant arose later in the trial and fewer cases (N = 18) were available for analysis. VE was 64% (-2, 87). ChAdOx1 nCoV-19 provided 95% protection (95% CI 61%, 99%) against hospitalisation due to COVID-19. In summary, we report that ChAdOx1 nCoV-19 protects against emerging variants in Brazil despite the presence of the spike protein mutation E484K.

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.