Symptomatic COVID-19 Cases Research Articles

SARS-CoV-2 variants induce increased inflammatory gene expression but reduced interferon responses and heme synthesis as compared with wild type strains

SARS-CoV-2 variants of concern (VOC) have been associated with increased viral transmission and disease severity. We investigated the mechanisms of pathogenesis caused by variants using a host blood transcriptome profiling approach. We analysed transcriptional signatures of COVID-19 patients comparing those infected with wildtype (wt), alpha, delta or omicron strains seeking insights into infection in Asymptomatic cases.Comparison of transcriptional profiles of Symptomatic and Asymptomatic COVID-19 cases showed increased differentially regulated gene (DEGs) of inflammatory, apoptosis and blood coagulation pathways, with decreased T cell and Interferon stimulated genes (ISG) activation. Between SARS-CoV-2 strains, an increasing number of DEGs occurred in comparisons between wt and alpha (196), delta (1425) or, omicron (2313) infections. COVID-19 cases with alpha or, delta variants demonstrated suppression transcripts of innate immune pathways. EGR1 and CXCL8 were highly upregulated in those infected with VOC; heme biosynthetic pathway genes (ALAS2, HBB, HBG1, HBD9) and ISGs were downregulated. Delta and omicron infections upregulated ribosomal pathways, reflecting increased viral RNA translation. Asymptomatic COVID-19 cases infected with delta infections showed increased cytokines and ISGs expression. Overall, increased inflammation, with reduced host heme synthesis was associated with infections caused by VOC infections, with raised type I interferon in cases with less severe disease.

Humoral and cellular immune response to AZD1222 /Covishield and BV152/Covaxin COVID-19 vaccines among adults in India

ABSTRACT Several COVID-19 vaccines were developed using different approaches to prevent both symptomatic COVID-19 cases and fatalities. The adults were vaccinated with two doses of AZD1222/Covishield (n = 77) [manufactured by Serum Institute of India Pvt Ltd] vaccine and BV152/Covaxin (n = 99) [manufactured by Bharat Biotech] vaccine. They were assessed for immune response at pre-vaccination, 1 month post first and 6 months post second dose for anti-SARS-CoV-2 IgG antibody, surrogate neutralizing antibody (NAbs), immune phenotypes, antigen specific NK, B and T cell response, their effector functionality by ELISPOT and plasma cytokine profile. Both vaccines elicited enhanced IgG antibody and Nab levels compared to the baseline. BV152/Covaxin, the whole virus inactivated vaccine exhibited higher IgG (70% vs 100%), Nab (90% vs 100%), and robust T cell (31% vs 96%) responses at 6 months post second dose compared to 1 month post first dose justifying the utility of the second dose. Detection of SARS-CoV-2 WV and S1 specific CD4+ central T cell memory response in AZD1222/Covishield vaccinee at 6 months post second dose and higher CD4+ and CD8+ naïve and central memory T cell response in BV152/Covaxin vaccinee at 1 month post first dose indicated the involvement of memory T cells. Persistent IgG and NAb responses along with IgG+B and IgG+memory B cells in AZD1222/Covishield recipients at 6 months post second dose indicated sustained immune memory response. Continued heightened IFN-γ secreting T cell response (ELISPOT) displayed by both the vaccine platforms could serve as a co correlate of protection, further to evaluation in follow up studies. Overall, our data suggest that coordinated functions of humoral and cellular branches of adaptive immunity may pave ways toward protective immunity against COVID-19.

Safety and Efficacy of Chyawanprash as a Prophylaxis Treatment for COVID-19: A Systematic Review and Meta-Analysis of Randomized Control Trials.

Amidst the multifaceted challenges posed by COVID-19, interest in complementary and alternative medicine (CAM) has risen. Chyawanprash (CP), an Ayurvedic formulation, is recognized for its multifunctional properties. This systematic review aims to evaluate its safety and effectiveness as a COVID-19 prophylactic.A literature search was conducted for articles published within the past three years from databases such as Cochrane Library, PubMed, and Google Scholar. A total of 1008 articles were identified, and 34 were included for full-text screening, resulting in five randomized controlled trials (RCTs) meeting the eligibility criteria. Meta-analysis was performed using a random effects model, with results represented in odds ratio (95% confidence intervals (CIs)), and publication bias presented through funnel plots.The five clinical trials conducted in India analyzed 153,343 participants. In the meta-analysis, the odds ratios for COVID-19-positive patients, COVID-19-positive in symptomatic patients, healthcare resource utilization (HCRU), and adverse events were 0.45 (95% CI 0.06-3.08, p = 0.41), 0.37 (95% CI 0.01-12.86, p = 0.58), 0.95 (95% CI 0.18-5.04, p = 0.95), and 0.94 (95% CI 0.63-1.40, p = 0.75) respectively. Notably, significant heterogeneity was observed among studies including both COVID-19-positive cases (I2= 80%, p = 0.007) and symptomatic COVID-19 cases (I2= 83%, p = 0.01), whereas non-significant zero heterogeneity was observed in HCRU (I2=0%, p = 0.74) and adverse events (I2= 0%, p = 1.00). The meta-analysis reveals a trendin the efficacy of CP as prophylaxis for COVID-19 treatments. However, owing to high heterogeneity and bias, further research is recommended.

A six-compartment model for COVID-19 with transmission dynamics and public health strategies.

The global crisis of the COVID-19 pandemic has highlighted the need for mathematical models to inform public health strategies. The present study introduces a novel six-compartment epidemiological model that uniquely incorporates a higher isolation rate for unreported symptomatic cases of COVID-19 compared to reported cases, aiming to enhance prediction accuracy and address the challenge of initial underreporting. Additionally, we employ optimal control theory to assess the cost-effectiveness of interventions and adapt these strategies to specific epidemiological scenarios, such as varying transmission rates and the presence of asymptomatic carriers. By applying this model to COVID-19 data from India (30 January 2020 to 24 November 2020), chosen to capture the initial outbreak and subsequent waves, we calculate a basic reproduction number of 2.147, indicating the high transmissibility of the virus during this period in India. A sensitivity analysis reveals the critical impact of detection rates and isolation measures on disease progression, showing the robustness of our model in estimating the basic reproduction number. Through optimal control simulations, we demonstrate that increasing isolation rates for unreported cases and enhancing detection reduces the spread of COVID-19. Furthermore, our cost-effectiveness analysis establishes that a combined strategy of isolation and treatment is both more effective and economically viable. This research offers novel insights into the efficacy of non-pharmaceutical interventions, providing a tool for strategizing public health interventions and advancing our understanding of infectious disease dynamics.

N-protein vaccine is effective against COVID-19: Phase 3, randomized, double-blind, placebo-controlled clinical trial

Despite the success of first-generation COVID-19 vaccines targeting the spike (S) protein, emerging SARS-CoV-2 variants have led to immune escape, reducing the efficacy of these vaccines. Additionally, some individuals are unable to mount an effective immune response to S protein-based vaccines. This has created a need for alternative vaccine strategies that are less susceptible to mutations and capable of providing broad and durable protection. This study aimed to evaluate the efficacy and safety of a novel COVID-19 vaccine based on the full-length recombinant nucleocapsid (N) protein of SARS-CoV-2. We conducted a prospective, multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial (NCT05726084) in Russia. Participants (n=5229) were adults aged 18 years and older, with a BMI of 18.5-30kg/m², and without significant clinical abnormalities. They were randomized in a 2:1 ratio to receive a single intramuscular dose of either the N protein-based vaccine (50µg) or placebo. Randomization was done through block randomization, and masking was ensured by providing visually identical formulations of vaccine and placebo. The primary outcome was the incidence of symptomatic COVID-19 confirmed by PCR more than 15 days after vaccination within a 180-day observation period, analyzed on an intention-to-treat basis. Between May 18, 2023, and August 9, 2023, 5229 participants were randomized, with 3486 receiving the vaccine and 1743 receiving the placebo. Eight cases of PCR-confirmed symptomatic COVID-19 occurred in the vaccine group (0.23%) compared to 27 cases in the placebo group (1.55%), yielding a vaccine efficacy of 85.2% (95% CI: 67.4-93.3; p<0.0001). Adverse events were mostly mild and included local injection site reactions. There were no vaccine-related serious adverse events. The N protein-based COVID-19 vaccine demonstrated significant efficacy and a favorable safety profile, suggesting it could be a valuable addition to the global vaccination effort, particularly in addressing immune escape variants and offering an alternative for those unable to respond to S protein-based vaccines. These results support the continued development and potential deployment of N protein-based vaccines in the ongoing fight against COVID-19.

Underreporting of Cases in the COVID-19 Outbreak of Borriana (Spain) during Mass Gathering Events in March 2020: A Cross-Sectional Study.

Determining the number of cases of an epidemic is the first function of epidemiological surveillance. An important underreporting of cases was observed in many locations during the first wave of the COVID-19 pandemic. To estimate this underreporting in the COVID-19 outbreak of Borriana (Valencia Community, Spain) in March 2020, a cross-sectional study was performed in June 2020 querying the public health register. Logistic regression models were used. Of a total of 468 symptomatic COVID-19 cases diagnosed in the outbreak through anti-SARS-CoV-2 serology, 36 cases were reported (7.7%), resulting in an underreporting proportion of 92.3% (95% confidence interval [CI], 89.5-94.6%), with 13 unreported cases for every reported case. Only positive SARS-CoV-2 polymerase chain reaction cases were predominantly reported due to a limited testing capacity and following a national protocol. Significant factors associated with underreporting included no medical assistance for COVID-19 disease, with an adjusted odds ratio [aOR] of 10.83 (95% CI 2.49-47.11); no chronic illness, aOR = 2.81 (95% CI 1.28-6.17); middle and lower social classes, aOR = 3.12 (95% CI 1.42-6.85); younger age, aOR = 0.97 (95% CI 0.94-0.99); and a shorter duration of illness, aOR = 0.98 (95% CI 0.97-0.99). To improve the surveillance of future epidemics, new approaches are recommended.

The impact of the COVID-19 vaccination programme on symptomatic and severe SARS-CoV-2 infection during a period of Omicron variant dominance in Ireland, December 2021 to March 2023.

BackgroundAs Ireland prepared for an autumn 2023 COVID-19 vaccination booster campaign, there was concern that vaccine fatigue would affect uptake, which has been abating.AimThis study aimed to quantify the direct impact of the COVID-19 vaccination programme in Ireland on averted COVID-19-related outcomes including symptomatic presentations to primary care/community testing centres, emergency department (ED) presentations, hospitalisations, intensive care unit (ICU) admissions and deaths, in individuals aged ≥ 50 years, during Omicron dominance.MethodsWe conducted a retrospective observational COVID-19 vaccine impact study in December 2021-March 2023 in Ireland. We used national data on notified outcomes and vaccine coverage, as well as vaccine effectiveness (VE) estimates, sourced from the World Health Organization's live systematic review of VE, to estimate the count and prevented fraction of outcomes in ≥ 50-year-olds averted by the COVID-19 vaccination programme in this age group.ResultsThe COVID-19 vaccination programme averted 48,551 symptomatic COVID-19 presentations to primary care/community testing centres (36% of cases expected in the absence of vaccination), 9,517 ED presentations (53% of expected), 102,160 hospitalisations (81% of expected), 3,303 ICU admissions (89% of expected) and 15,985 deaths (87% of expected).ConclusionsWhen Omicron predominated, the COVID-19 vaccination programme averted symptomatic and severe COVID-19 cases, including deaths due to COVID-19. In line with other international vaccine impact studies, these findings emphasise the benefits of COVID-19 vaccination for population health and the healthcare system and are relevant for informing COVID-19 booster vaccination programmes, pandemic preparedness and communicating the reason for and importance of COVID-19 vaccination in Ireland and internationally.

Efficacy, immunogenicity, and safety of a monovalent mRNA vaccine, ABO1020, in adults: A randomized, double-blind, placebo-controlled, phase 3 trial

ABO1020 is a monovalent COVID-19 mRNA vaccine. Results from a phase 1 trial showed ABO1020 was safe and well tolerated, and phase 3 trials to evaluate the efficacy, immunogenicity, and safety of ABO1020 in healthy adults are urgently needed. We conducted a multinational, randomized, placebo-controlled, double-blind, phase 3 trial among healthy adults (ClinicalTrials.gov: NCT05636319). Participants were randomly assigned (1:1) to receive either 2 doses of ABO1020 (15μg per dose) or placebo, administered 28days apart. The primary endpoint was the vaccine efficacy in preventing symptomatic COVID-19 cases that occurred at least 14days post-full vaccination. The second endpoint included the neutralizing antibody titers against Omicron BA.5 and XBB and safety assessments. A total of 14,138 participants were randomly assigned to receive either vaccine or placebo (7,069 participants in each group). A total of 366 symptomatic COVID-19 cases were confirmed 14days after the second dose among 93 participants in the ABO1020 group and 273 participants in the placebo group, yielding a vaccine efficacy of 66.18% (95% confidence interval: 57.21-73.27, p<0.0001). A single dose or two doses of ABO1020 elicited potent neutralizing antibodies against both BA.5 and XBB.1.5. The safety profile of ABO1020 was characterized by transient, mild-to-moderate fever, pain at the injection site, and headache. ABO1020 was well tolerated and conferred 66.18% protection against symptomatic COVID-19 in adults. National Key Research and Development Project of China, Innovation Fund for Medical Sciences from the CAMS, National Natural Science Foundation of China.

Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B*15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B*15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the US (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B*15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

COVID-19 Vaccine Efficacy in Participants With Weakened Immune Systems From 4 Randomized Controlled Trials.

Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are highly efficacious at preventing severe disease in the general population, current data are lacking regarding vaccine efficacy (VE) for individuals with mild immunocompromising conditions. A post hoc, cross-protocol analysis of participant-level data from the blinded phase of four randomized, placebo-controlled, coronavirus disease 2019 (COVID-19) vaccine phase 3 trials (Moderna, AstraZeneca, Janssen, and Novavax) was performed. We defined a "tempered immune system" (TIS) variable via a consensus panel based on medical history and medications to determine VE against symptomatic and severe COVID-19 cases in TIS participants versus non-TIS individuals starting at 14 days after completion of the primary series through the blinded phase for each of the 4 trials. An analysis of participants living with well-controlled human immunodeficiency virus was conducted using the same methods. A total of 3852/30 351 (12.7%) Moderna participants, 3088/29 868 (10.3%) Novavax participants, 3549/32 380 (11.0%) AstraZeneca participants, and 5047/43 788 (11.5%) Janssen participants were identified as having a TIS. Most TIS conditions (73.9%) were due to metabolism and nutritional disorders. Vaccination (vs placebo) significantly reduced the likelihood of symptomatic and severe COVID-19 for all participants for each trial. VE was not significantly different for TIS participants versus non-TIS for either symptomatic or severe COVID-19 for each trial, nor was VE significantly different in the symptomatic endpoint for participants with human immunodeficiency virus. For individuals with mildly immunocompromising conditions, there is no evidence of differences in VE against symptomatic or severe COVID-19 compared with those with non-TIS in the 4 COVID-19 vaccine randomized controlled efficacy trials.

The impact of polymorphic variants of interferon receptor genes on COVID-19 severity and antibiotic resistance

Single nucleotide substitutions in gene sequence associated with conformational changes in protein receptor or in expression of interferon receptors may explain variations in human susceptibility to infection and severity of COVID-19 along with other well-known risk factors. The study aimed to investigate associations between polymorphic variants of interferon receptor genes, COVID-19 severity and prevalence of antibiotic resistance genes in the gut microbiota. Materials and methods. The study was conducted using a random sample of Arkhangelsk population aged 42 to 76 years (n = 305). The research involved gathering COVID-19 data from the Federal Register, conducting blood tests for SARS-CoV-2 antibodies and polymorphic interferon receptor gene variants, and identifying antibiotic resistance genes in stool samples. Results. During the first 12–15 months of the COVID-19 pandemic, 17.4% of the study participants had symptomatic COVID-19, while 32.8% were asymptomatic. By the Autumn of 2022, symptomatic COVID-19 cases rose up to 36.4%, while asymptomatic cases increased to 61.3%. We reveal an association between the CC genotype of the IFNAR1 gene rs2257167 variant, the presence of the T allele of IFNAR2 gene rs2229207 variant, the CCTT haplotype and symptomatic COVID-19. The GCTC haplotype was associated with pneumonia and COVID-19 severity. In November 2022, macrolide resistance genes were observed in 98.4% of cases, whereas those to beta-lactams and glycopeptides — in 26.9% and 13.8% cases, respectively. Resistance to three classes of antibiotics was observed in 4.9% and was more frequently detected in individuals with the ССТТ haplotype. Genes encoding beta-lactamases were more often found in individuals with the GCTC haplotype, those who had COVID-19 with pneumonia and those who received hospital treatment. Glycopeptide resistance genes were associated with the CC genotype of the rs2257167 variant of IFNAR1 gene. Conclusion. We identified genetic determinants of susceptibility, symptomatic infection and COVID-19 severity. The associations between polymorphic variants of interferon receptor genes and COVID-19 severity can be used to identify people with a genetic predisposition to severe infection and to determine priority groups for vaccination, including the prevention of antibiotic resistance in complicated course of viral infections.

Assessment of vaccination and underreporting on COVID-19 infections in Turkey based on effective reproduction number

In this paper, we introduce a SEIR-type COVID-19 model where the infected class is further divided into subclasses with individuals in intensive care (ICUs) and ventilation units. The model is calibrated with the symptomatic COVID-19 cases, deaths, and the number of patients in ICUs and ventilation units as reported by Republic of Turkey, Ministry of Health for the period 11 March 2020 through 30 May 2020 when the nationwide lockdown is in order. COVID-19 interventions in Turkey are incorporated into the model to detect the future trend of the outbreak accurately. We tested the effect of underreporting and we found that the peaks of the disease differ significantly depending on the rate of underreporting, however, the timing of the peaks remains constant. The lockdown is lifted on 1 June, and the model is modified to include a time-dependent transmission rate which is linked to the effective reproduction number [Formula: see text] through basic reproduction number [Formula: see text]. The modified model captures the changing dynamics and peaks of the outbreak successfully. With the onset of vaccination on 13 January 2021, we augment the model with the vaccination class to investigate the impact of vaccination rate and efficacy. We observe that vaccination rate is a more critical parameter than the vaccine efficacy to eliminate the disease successfully.

Moana: Alternate surveillance for COVID-19 in a Unique Population (MASC-UP)

ObjectiveCreate a longitudinal, multi-modal and multi-level surveillance cohort that targets early detection of symptomatic and asymptomatic COVID-19 cases among Native Hawaiian and Pacific Islander adults in the Continental US and identify effective modalities for participatory disease surveillance and sustainably integrate them into ongoing COVID-19 and other public health surveillance efforts. Materials and methodsWe recruited cohorts from three sites: Federal Way, WA; Springdale, AR; and remotely. Participants received a survey that included demographic characteristics and questions regarding COVID-19. Participants completed symptom checks via text message every month and recorded their temperature daily using a Kinsa smart thermometer. ResultsRecruitment and data collection is ongoing. Presently, 441 adults have consented to participate. One-third of participants were classified as essential workers during the pandemic. DiscussionOver the past 18 months, we have improved our strategies to elicit better data from participants and have learned from some of the weaknesses in our initial deployment of this type of surveillance system. Other limitations stem from historic inequities and barriers which limited Native Hawaiian and Pacific Island representation in academic and clinical environments. One manifestation of this was the limited ability to provide study materials and support in multiple languages. We hope that continued partnership with the community will allow further opportunities to help restore trust in academic and medical institutions, thus generating knowledge to advance health equity. ConclusionThis participatory disease surveillance mechanism complements traditional surveillance systems by engaging underserved communities. We may also gain insights generalizable to other pathogens of concern.

Efficacy of Oxford-AstraZeneca (ChAdOx1 CoV-19) vaccine against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) cases, hospital admissions, type of variants, and deaths.

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) epidemic has instigated enormous damage to the global healthcare system and economies. A large number of vaccines have been developed. However, confidence in any COVID-19 vaccine is essential for its sustainable success. The present study aimed to investigate the efficacy of the Oxford-AstraZeneca (ChAdOx1 CoV-19) vaccine against SARS-COV-2 cases, hospital admissions, type of variants and deaths. This study recorded data using electronic platforms PubMed, Web of Science, World Health Organization, US-Food and Drug Authorities-FDA, Facts sheets, and Pharmaceutical Websites. Initially, 278 articles and reports were identified, and after revising the abstracts, 39 studies, clinical trials and organizations, reports were selected for a detailed analysis. The efficacy of the Oxford-AstraZeneca COVID-19 vaccine against symptomatic COVID-19 cases after the first dose was 60.59% (p=0.00001) and after the second dose was 66.84% (p=0.00001). The highest efficacy was against the Alpha variant 58.80% (p=0.00001) and the lowest efficacy was against the Beta variant 30.83% (p=0.00001). However, the overall efficacy against the SARS-CoV-2 variants after the first dose was 49.20%. The highest efficiency of SARS-CoV-2 variants after the second dose against the Beta (B.1.351) variant was 90.34% (p=0.00001), while the lowest efficacy was against the Omicron (B.1.1.529) variant 46.46% (p=0.00001), with overall efficacy against SARS-CoV-2-2 variants after the second dose 73.73%. The highest efficacy against emergency admission was 94.42% (p=0.00001), while the lowest efficacy was 86.57% (p=0.00001), with overall efficacy against ICU, hospital, and emergency admissions after the second dose was 87.74%. Furthermore, the efficacy of the Oxford-AstraZeneca vaccine against deaths after the second dose was 87.44% (p=0.00001). The efficacy of the Oxford-AstraZeneca COVID-19 vaccine against symptomatic COVID-19 cases, various variants, ICU, and emergency admissions, and against deaths was high. The present study results provide valuable insights for healthcare workers, policymakers, and researchers about the precise efficacy levels against symptomatic cases, hospitalization, and mortality across the diverse populations and age groups.

Factors associated with delayed diagnosis of symptomatic adult COVID-19 cases presenting to primary care: a population-wide study during transition from Delta to Omicron BA.1 in Singapore

During pandemics, avoiding time delay in diagnosing infection is crucial. We evaluated factors associated with delayed diagnosis of symptomatic SARS-CoV-2 infection in a national cohort of adult Singaporeans, during which emergence of the more transmissible Omicron variant shifted pandemic management towards endemicity. Retrospective cross-sectional study amongst all adult Singaporeans diagnosed with symptomatic SARS-CoV-2 infection during the transition from Delta to Omicron BA.1 (September 2021-February 2022). SARS-CoV-2 testing was fully subsidised and compulsory for all symptomatic individuals presenting at primary care. Results and demographic information were extracted from national databases. Time to diagnosis was defined as days from symptom-onset to diagnosis (date of first positive SARS-CoV-2 test); dichotomising into no delay (≤24h from symptom-onset) and delay >24h. Multivariable logistic regression was utilised to assess factors associated with delay >24h, and association of delay >24h with progression to severe COVID-19. Of 149,063 Singaporean adults presenting with symptomatic SARS-CoV-2 infection, 75.9% (113,195/149,063) were diagnosed within 24h of symptom-onset. On multivariable analysis, female gender, older age (>60 years), Chinese (vs. Malay) ethnicity, socioeconomic status (housing type), primary care characteristics, presentation during Omicron BA.1 (vs. Delta), symptom-onset on Friday/Saturday (vs. Monday), and not having completed a primary vaccination series were independently associated with higher odds of delay >24h. Delay >24h was independently associated with severe COVID-19 (adjusted odds-ratio, aOR=1.45, 95% CI=1.27-1.65, p<0.001). At-risk populations (unvaccinated, age >60 years) had higher odds of delay in diagnosis. Delay >24h in diagnosis was independently associated with severe COVID-19. This study was not grant-funded.

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, parallel, randomised, modified double-blind, placebo-controlled trial

COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern. This study aimed to describe the clinical efficacy and safety of a bivalent SARS-CoV-2 recombinant protein vaccine as a two-injection primary series during a period of circulation of the omicron (B.1.1.529) variant. We conducted a phase 3, parallel, randomised, modified double-blind, placebo-controlled trial in adults aged 18 years or older at 54 clinical research centres in eight countries (Colombia, Ghana, India, Kenya, Mexico, Nepal, Uganda, and Ukraine). Participants were recruited from the community and randomly assigned (1:1) by use of an interactive response technology system to receive two intramuscular 0·5 mL injections, 21 days apart, of the bivalent vaccine (5 μg of ancestral [D614] and 5 μg of beta [B.1.351] variant spike protein, with AS03 adjuvant) or placebo (0·9% normal saline). All participants, outcome assessors, and laboratory staff performing assays were masked to group assignments; those involved in the preparation and administration of the vaccines were unmasked. Participants were stratified by age (18-59 years and ≥60 years) and baseline SARS-CoV-2 rapid serodiagnostic test positivity. Symptomatic COVID-19 was defined as laboratory-confirmed (via nucleic acid amplification test or PCR test) COVID-19 with COVID-19-like illness symptoms. The primary efficacy endpoint was the clinical efficacy of the bivalent vaccine for prevention of symptomatic COVID-19 at least 14 days after the second injection (dose 2). Safety was assessed in all participants receiving at least one injection of the study vaccine or placebo. This trial is registered with ClinicalTrials.gov (NCT04904549) and is closed to recruitment. Between Oct 19, 2021, and Feb 15, 2022, 13 002 participants were enrolled and randomly assigned to receive the first dose of the study vaccine (n=6512) or placebo (n=6490). 12 924 participants (6472 in the vaccine group and 6452 in the placebo group) received at least one study injection, of whom 7542 (58·4%) were male and 9693 (75·0%) were SARS-CoV-2 non-naive. Of these 12 924 participants, 11 543 (89·3%) received both study injections (5788 in the vaccine group and 5755 in the placebo group). The efficacy-evaluable population after dose 2 comprised 11 416 participants (5736 in the vaccine group and 5680 in the placebo group). The median duration of follow-up was 85 days (IQR 50-95) after dose 1 and 58 days (29-70) after dose 2. 121 symptomatic COVID-19 cases were reported at least 14 days after dose 2 (32 in the vaccine group and 89 in the placebo group), with an overall vaccine efficacy of 64·7% (95% CI 46·6 to 77·2). Vaccine efficacy against symptomatic COVID-19 was 75·1% (95% CI 56·3 to 86·6) in SARS-CoV-2 non-naive participants and 30·9% (-39·3 to 66·7) in SARS-CoV-2-naive participants. Viral genome sequencing identified the infecting strain in 68 (56·2%) of 121 cases (omicron [BA.1 and BA.2] in 63; delta in four; and both omicron and delta in one). Immediate unsolicited adverse events were reported by four (<0·1%) participants in the vaccine group and seven (0·1%) participants in the placebo group. Immediate unsolicited adverse reactions within 30 min after any injection were reported by four (<0·1%) participants in the vaccine group and six (<0·1%) participants in the placebo group. In the reactogenicity subset with available data, solicited reactions (solicited injection-site reactions and solicited systemic reactions) within 7 days after any injection occurred in 1398 (57·8%) of 2420 vaccine recipients and 983 (40·9%) of 2403 placebo recipients. Grade 3 solicited reactions were reported by 196 (8·1%; 95% CI 7·0 to 9·3) of 2420 vaccine recipients and 118 (4·9%; 4·1 to 5·9) of 2403 placebo recipients within 7 days after any injection, with comparable frequencies after dose 1 and dose 2 in the vaccine group. At least one serious adverse event occurred in 30 (0·5%) participants in the vaccine group and 26 (0·4%) in the placebo group. The proportion of adverse events of special interest and deaths was less than 0·1% in both study groups. No adverse event of special interest, serious adverse event, or death was deemed to be treatment related. There were no reported cases of thrombosis with thrombocytopenia syndrome, myocarditis, pericarditis, Bell's Palsy, or Guillain-Barré syndrome, or other immune-mediated diseases. The bivalent variant vaccine conferred heterologous protection against symptomatic SARS-CoV-2 infection in the epidemiological context of the circulating contemporary omicron variant. These findings suggest that vaccines developed with an antigen from a non-predominant strain could confer cross-protection against newly emergent SARS-CoV-2 variants, although further investigation is warranted. Sanofi, US Biomedical Advanced Research and Development Authority, and the US National Institute of Allergy and Infectious Diseases.

Comparative effectiveness and duration of protection of ChAdOx1, CoronaVac, BNT162b2, mRNA-1273, and Ad26.COV2.S COVID-19 vaccines for symptomatic and hospitalized Mu, Delta, and Omicron: A test-negative case-control study

ObjectiveWe carried out a study to estimate the vaccine effectiveness (VE) of homologous vaccination schedules against COVID-19, using data from mandatory information systems from Bogota, Colombia. MethodsA test-negative case-control study in adults from Bogota (Colombia), between March 1st of 2021 and February 25th of 2022. We assess VE among symptomatic COVID-19 cases during the Mul, Delta, and Omicron predominance periods in Bogota, with controls matched by sex, age (±5 years), and date of testing (±7 days), using a case:control ratio of 1:1. We selected homologous vaccination schedules with ChAdOx1, CoronaVac, BNT162b2, mRNA-1273, and Ad26.COV2.S. VE was reported as one minus the odds ratio in adjusted conditional logistic regressions, with their 95% confidence intervals (CI). A p-value < 0.05 was considered statistically significant. Results52,913 cases were matched to controls, 16,722 for Mu, 14,094 for Delta, and 22,097 for Omicron. VE was high against COVID-19 during Mu weeks with full vaccination using the monovalent BNT162b2 (VE: 69; 95% CI, 65 to 72) vaccine and ChAdOx1 (VE: 64; 95% CI, 31 to 81) and significantly lower with CoronaVac (P < 0.001) and Ad26.COV2.S (P = 0.005). During Delta, VE against COVID-19 was higher with BNT162b2 (VE: 55; 95% CI, 51 to 58). The VE for COVID-19 cases during Omicron was higher with a booster dose of monovalent BNT162b2 (VE: 45; 95% CI, 34 to 54). The VE of primary series and booster for ChAdOx1, Ad26.COV2.S, and CoronaVac did not show protection for Omicron. ConclusionOur study provides further evidence on the protective effect of mRNA vaccines for Omicron, and warrant that the duration of protection against symptomatic infection may last for only a few months.

Prevalence and cost of hospitalized patients with asymptomatic COVID-19 in 2020 in Spain.

COVID-19 transmission has been characterized by the presence of asymptomatic patients. Additionally, most studies evaluating costs focus on symptomatic COVID-19 cases. To describe the prevalence, characteristics, and costs of asymptomatic COVID-19 cases at admission in Spanish hospitals in 2020. A nationwide study was performed, and data of hospitalized patients were collected of the Minimum Basic Data Set in Spain during 2020. Patients with COVID-19 codes as a primary and as a secondary diagnosis at admission were selected. Variables collected included age, sex, length of stay, in-hospital death, admission, length of stay and death in intensive care unit, mechanical ventilation and ventilatory assistance. COVID-19 related hospital costs were calculated using diagnosis-related groups from the Minimum Basic Data Set. Patients and costs were disaggregated by sex, age group, intensive care unit admission and epidemic wave (first or second) and main diagnosis. A total of 14,742 patients were admitted with asymptomatic COVID-19 in Spanish hospitals representing 6.35% of all COVID-19 admitted patients. The total cost of admissions with asymptomatic COVID-19 was €105,933,677.6 with a mean cost per patient of €7,185.8 with higher mean cost in the first wave despite only 2.7% of cases were found during that time. Based on primary diagnosis, the higher number of cases of asymptomatic COVID-19 were found in "Pregnancy, childbirth and the puerperium" followed by "diseases of the circulatory system". There was a high prevalence of asymptomatic cases during screening at admission process in Spanish hospitals in 2020. The highest number of cases was found among the group of "pregnancy, childbirth, and puerperium" followed by "diseases of the circulatory system." The higher costs might be due not only to the main pathology at admission but to the associated healthcare provisions needed in case of positive COVID-19 testing.

Comparison of pretrained transformer-based models for influenza and COVID-19 detection using social media text data in Saskatchewan, Canada.

The use of social media data provides an opportunity to complement traditional influenza and COVID-19 surveillance methods for the detection and control of outbreaks and informing public health interventions. The first aim of this study is to investigate the degree to which Twitter users disclose health experiences related to influenza and COVID-19 that could be indicative of recent plausible influenza cases or symptomatic COVID-19 infections. Second, we seek to use the Twitter datasets to train and evaluate the classification performance of Bidirectional Encoder Representations from Transformers (BERT) and variant language models in the context of influenza and COVID-19 infection detection. We constructed two Twitter datasets using a keyword-based filtering approach on English-language tweets collected from December 2016 to December 2022 in Saskatchewan, Canada. The influenza-related dataset comprised tweets filtered with influenza-related keywords from December 13, 2016, to March 17, 2018, while the COVID-19 dataset comprised tweets filtered with COVID-19 symptom-related keywords from January 1, 2020, to June 22, 2021. The Twitter datasets were cleaned, and each tweet was annotated by at least two annotators as to whether it suggested recent plausible influenza cases or symptomatic COVID-19 cases. We then assessed the classification performance of pre-trained transformer-based language models, including BERT-base, BERT-large, RoBERTa-base, RoBERT-large, BERTweet-base, BERTweet-covid-base, BERTweet-large, and COVID-Twitter-BERT (CT-BERT) models, on each dataset. To address the notable class imbalance, we experimented with both oversampling and undersampling methods. The influenza dataset had 1129 out of 6444 (17.5%) tweets annotated as suggesting recent plausible influenza cases. The COVID-19 dataset had 924 out of 11939 (7.7%) tweets annotated as inferring recent plausible COVID-19 cases. When compared against other language models on the COVID-19 dataset, CT-BERT performed the best, supporting the highest scores for recall (94.8%), F1(94.4%), and accuracy (94.6%). For the influenza dataset, BERTweet models exhibited better performance. Our results also showed that applying data balancing techniques such as oversampling or undersampling method did not lead to improved model performance. Utilizing domain-specific language models for monitoring users' health experiences related to influenza and COVID-19 on social media shows improved classification performance and has the potential to supplement real-time disease surveillance.

Combination of spironolactone and sitagliptin improves clinical outcomes of outpatients with COVID-19: a prospective cohort study.

There are evidences showing that sitagliptin and spironolactone can potentially improve the clinical outcomes of COVID-19 cases. In this observational study on acutely symptomatic outpatient COVID-19 cases, we investigated the effects of spironolactone and sitagliptin on the outcomes of the disease. This is a prospective, naturally randomized cohort study. We followed mild to moderate symptomatic COVID-19 patients, who were treated with either combination (spironolactone 100mg daily and sitagliptin 100mg daily) or standard (steroid, antiviral and/or supportive care) therapy up to 30days. The primary outcome was hospitalization rate. The secondary outcomes included ER visit, duration of disease, and complications, such as hypoglycemia, low blood pressure or altered mental status. Of the 206 patients referred to clinics randomly, 103 received standard therapy and 103 treated with combination therapy. There were no significant differences in baseline characteristics, except for slightly higher clinical score in control group (6.92 ± 4.01 control, 4.87 ± 2.92 combination; P < 0.0001). Treatment with combination therapy was associated with lower admission rate (5.8% combination, 22.3% control; P = 0.0011), ER visits (7.8% combination, 23.3% control; P = 0.0021) and average duration of symptoms (6.67 ± 2.30days combination, 18.71 ± 6.49days control; P ≤ 0.0001). The combination of sitagliptin and spironolactone reduced duration of COVID infection and hospital visits better than standard therapeutic approaches in outpatients with COVID-19. The effects of combination of sitagliptin and spironolactone in COVID-19 patients should be further verified in a double-blind, randomized, placebo-controlled trial.