SARS-CoV-2 and Influenza Virus Co-Infection Cases Identified through ILI/SARI Sentinel Surveillance: A Pan-India Report

SARS-CoV-2/influenza virus co-infection studies have focused on hospitalized patients who usually had grave sequelae. Here, we report SARS-CoV-2/influenza virus co-infection cases from both community and hospital settings reported through integrated ILI/SARI (Influenza Like Illness/Severe Acute Respiratory Infection) sentinel surveillance established by the Indian Council of Medical Research. We describe the disease progression and outcomes in these cases. Out of 13,467 samples tested from 4 July 2021–31 January 2022, only 5 (0.04%) were of SARS-CoV-2/influenza virus co-infection from 3 different sites in distinct geographic regions. Of these, three patients with extremes of age required hospital admission, but none required ICU admission or mechanical ventilation. No mortality was reported. The other two co-infection cases from community settings were managed at home. This is the first report on SARS-CoV-2/Influenza virus co-infection from community as well as hospital settings in India and shows that influenza viruses are circulating in the community even during COVID-19. The results emphasize the need for continuous surveillance for multiple respiratory pathogens for effective public health management of ILI/SARI cases in line with the WHO (World Health Organization) recommendations.     

Omicron Sub-Lineages (BA.1.1.529 + BA.*) Current Status in Ecuador

The Omicron variant of SARS-CoV-2 is the latest pandemic lineage causing COVID-19. Despite having a vaccination rate ≥85%, Ecuador recorded a high incidence of Omicron from December 2021 to March 2022. Since Omicron emerged, it has evolved into multiple sub-lineages with distinct prevalence in different regions. In this work, we use all Omicron sequences from Ecuador available at GISAID until March 2022 and the software Nextclade and Pangolin to identify which lineages circulate in this country. We detected 12 different sub-lineages (BA.1, BA.1.1, BA.1.1.1, BA.1.1.14, BA.1.1.2, BA.1.14, BA.1.15, BA.1.16, BA.1.17, BA.1.6, BA.2, BA.2.3), which have been reported in Africa, America, Europe, and Asia, suggesting multiple introduction events. Sub-lineages BA.1 and BA.1.1 were the most prevalent. Genomic surveillance must continue to evaluate the dynamics of current sub-lineages, the early introduction of new ones and vaccine efficacy against evolving SARS-CoV-2.     

The impact of the SARS-CoV-2 pandemic on global influenza surveillance: Insights from 18 National Influenza Centers based on a survey conducted between November 2021 and March 2022

Background

National Influenza Centers (NICs) have played a crucial role in the surveillance of SARS-CoV-2. The FluCov project, covering 22 countries, was initiated to monitor the impact of the SARS-CoV-2 pandemic on influenza activity.

Methods

This project consisted of an epidemiological bulletin and NIC survey. The survey, designed to assess the impact of the pandemic on the influenza surveillance system, was shared with 36 NICs located across 22 countries. NICs were invited to reply between November 2021 and March 2022.

Results

We received 18 responses from NICs in 14 countries. Most NICs (76%) indicated that the number of samples tested for influenza decreased. Yet, many NICs (60%) were able to increase their laboratory testing capacity and the “robustness” (e.g., number of sentinel sites) (59%) of their surveillance systems. In addition, sample sources (e.g., hospital or outpatient setting) shifted. All NICs reported a higher burden of work following the onset of the pandemic, with some NICs hiring additional staff or partial outsourcing to other institutes or departments. Many NICs anticipate the future integration of SARS-CoV-2 surveillance into the existing respiratory surveillance system.

Discussion

The survey shows the profound impact of SARS-CoV-2 on national influenza surveillance in the first 27 months of the pandemic. Surveillance activities were temporarily disrupted, whilst priority was given to SARS-CoV-2. However, most NICs have shown rapid adaptive capacity underlining the importance of strong national influenza surveillance systems. These developments have the potential to benefit global respiratory surveillance in the years to come; however, questions about sustainability remain.     

Prior SARS-CoV-2 infection and COVID-19 vaccine effectiveness against outpatient illness during widespread circulation of SARS-CoV-2 Omicron variant,US Flu VE network

Background

We estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI).

Methods

During SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARS-CoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status.

Results

Four hundred fifty-five (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%–99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%–76%) against Omicron; VE against Delta could not be estimated.

Conclusions

Three mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants.     

Genomic and epidemiological report of the recombinant XJ lineage SARS-CoV-2 variant,detected in northern Finland,January 2022

Recombinant sequences of the SARS-CoV-2 Omicron variant were detected in surveillance samples collected in north-western Finland in January 2022. We detected 191 samples with an identical genome arrangement in weeks 3 to 11, indicating sustained community transmission. The recombinant lineage has a 5’-end of BA.1, a recombination breakpoint between orf1a and orf1b (nucleotide position 13,296–15,240) and a 3’-end of BA.2 including the S gene. We describe the available genomic and epidemiological data about this currently circulating recombinant XJ lineage.     

The impact of SARS-CoV-2 on respiratory syndromic and sentinel surveillance in Israel, 2020: a new perspective on established systems

BackgroundThe COVID-19 pandemic presented new challenges for the existing respiratory surveillance systems, and adaptations were implemented. Systematic assessment of the syndromic and sentinel surveillance platforms during the pandemic is essential for understanding the value of each platform in the context of an emerging pathogen with rapid global spread.AimWe aimed to evaluate systematically the performance of various respiratory syndromic surveillance platforms and the sentinel surveillance system in Israel from 1 January to 31 December 2020.MethodsWe compared the 2020 syndromic surveillance trends to those of the previous 3 years, using Poisson regression adjusted for overdispersion. To assess the performance of the sentinel clinic system as compared with the national SARS-CoV-2 repository, a cubic spline with 7 knots and 95% confidence intervals were applied to the sentinel network''s weekly percentage of positive SARS-CoV-2 cases.ResultsSyndromic surveillance trends changed substantially during 2020, with a statistically significant reduction in the rates of visits to physicians and emergency departments to below previous years'' levels. Morbidity patterns of the syndromic surveillance platforms were inconsistent with the progress of the pandemic, while the sentinel surveillance platform was found to reflect the national circulation of SARS-CoV-2 in the population.ConclusionOur findings reveal the robustness of the sentinel clinics platform for the surveillance of the main respiratory viruses during the pandemic and possibly beyond. The robustness of the sentinel clinics platform during 2020 supports its use in locations with insufficient resources for widespread testing of respiratory viruses.     

Estimating SARS-CoV-2 infections and associated changes in COVID-19 severity and fatality

Background

The difficulty in identifying SARS-CoV-2 infections has not only been the major obstacle to control the COVID-19 pandemic but also to quantify changes in the proportion of infections resulting in hospitalization, intensive care unit (ICU) admission, or death.

Methods

We developed a model of SARS-CoV-2 transmission and vaccination informed by official estimates of the time-varying reproduction number to estimate infections that occurred in Italy between February 2020 and 2022. Model outcomes were compared with the Italian National surveillance data to estimate changes in the SARS-CoV-2 infection ascertainment ratio (IAR), infection hospitalization ratio (IHR), infection ICU ratio (IIR), and infection fatality ratio (IFR) in five different sub-periods associated with the dominance of the ancestral lineages and Alpha, Delta, and Omicron BA.1 variants.

Results

We estimate that, over the first 2 years of pandemic, the IAR ranged between 15% and 40% (range of 95%CI: 11%–61%), with a peak value in the second half of 2020. The IHR, IIR, and IFR consistently decreased throughout the pandemic with 22–44-fold reductions between the initial phase and the Omicron period. At the end of the study period, we estimate an IHR of 0.24% (95%CI: 0.17–0.36), IIR of 0.015% (95%CI: 0.011–0.023), and IFR of 0.05% (95%CI: 0.04–0.08).

Conclusions

Since 2021, changes in the dominant SARS-CoV-2 variant, vaccination rollout, and the shift of infection to younger ages have reduced SARS-CoV-2 infection ascertainment. The same factors, combined with the improvement of patient management and care, contributed to a massive reduction in the severity and fatality of COVID-19.     

Epidemiology and molecular characterization of influenza viruses in Burkina Faso,sub‐Saharan Africa

Background

The importance of influenza viruses in respiratory infections in sub‐Saharan Africa has been historically overlooked, including in Burkina Faso.

Objectives

This study therefore aimed at evaluating the prevalence and seasonal occurrence of influenza viruses in children under 5 years old, at risk of influenza‐related complications, presenting with influenza‐like illness (ILI) or severe acute respiratory infection (SARI). The study also aimed at identifying the periods with increased influenza transmission for vaccination recommendations in Burkina Faso.

Methods

From January 2014 to December 2015, ILI and SARI (2015 only) patients were recruited in six healthcare centers in Burkina Faso. Influenza A and B molecular detection and subtyping were performed. Clade clustering of a subset of A(H1N1)pdm09 and A(H3N2) strains was deduced by performing phylogenetic analyses on hemagglutinin gene sequences. Weekly surveillance data from FluNet (2011‐2013; 2016) and this study (2014‐2015) were used to identify periods of increased influenza activity.

Results

Influenza A and B viruses were detected in 15.1% (112 of 743) of ILI and 6.6% (12 of 181) of SARI patients. Overall, influenza A viruses were largely predominant (81 of 124, 65.3%), with 69.1% of A(H3N2) and 30.9% of A(H1N1)pdm09 strains. Four waves of increased transmission were identified in 2014‐2015, each dominated by different influenza subtypes and clades. Between 2011 and 2016, periods of increased influenza activity varied in their frequency, duration, and timing.

Conclusion

Influenza A and B viruses were detected in a substantial number of ILI and SARI cases in Burkina Faso. Vaccination in September‐October would likely protect the highest number of patients.     

COVID-19 vaccine effectiveness against severe disease from SARS-CoV-2 Omicron BA.1 and BA.2 subvariants – surveillance results from southern Sweden,December 2021 to March 2022

We compared vaccine effectiveness against severe COVID-19 between December 2021 and March 2022 when Omicron BA.1 and BA.2 were the dominating SARS-CoV-2 variants in Scania county, Sweden. Effectiveness remained above 80% after the transition from BA.1 to BA.2 among people with at least three vaccine doses but the point estimate decreased markedly to 54% among those with only two doses. Protection from prior infection was also lower after the transition to BA.2. Booster vaccination seems necessary to maintain sufficient protection.     

Risk factors associated with fatal influenza,Romania, October 2009 – May 2011

Background

Limited data are available from Central and Eastern Europe on risk factors for severe complications of influenza. Such data are essential to prioritize prevention and treatment resources and to adapt influenza vaccination recommendations.

Objectives

To use sentinel surveillance data to identify risk factors for fatal outcomes among hospitalized patients with severe acute respiratory infections (SARI) and among hospitalized patients with laboratory-confirmed influenza.

Methods

Retrospective analysis of case-based surveillance data collected from sentinel hospitals in Romania during the 2009/2010 and 2010/2011 winter influenza seasons was performed to evaluate risk factors for fatal outcomes using multivariate logistic regression.

Results

During 2009/2010 and 2010/2011, sentinel hospitals reported 661 SARI patients of which 230 (35%) tested positive for influenza. In the multivariate analyses, infection with influenza A(H1N1)pdm09 was the strongest risk factor for death among hospitalized SARI patients (OR: 6·6; 95% CI: 3·3–13·1). Among patients positive for influenza A(H1N1)pdm09 virus infection (n = 148), being pregnant (OR: 7·1; 95% CI: 1·6–31·2), clinically obese (OR: 2·9;95% CI: 1·6–31·2), and having an immunocompromising condition (OR: 3·7;95% CI: 1·1–13·4) were significantly associated with fatal outcomes.

Conclusion

These findings are consistent with several other investigations of risk factors associated with influenza A(H1N1)pdm09 virus infections. They also support the more recent 2012 recommendations by the WHO Strategic Advisory Group of Experts on Immunization (SAGE) that pregnant women are an important risk group for influenza vaccination. Ongoing sentinel surveillance can be useful tool to monitor risk factors for complications of influenza virus infections during each influenza season, and pandemics as well.     

A broad and potent neutralization epitope in SARS-related coronaviruses

Many neutralizing antibodies (nAbs) elicited to ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through natural infection and vaccination have reduced effectiveness to SARS-CoV-2 variants. Here, we show that therapeutic antibody ADG20 is able to neutralize SARS-CoV-2 variants of concern (VOCs) including Omicron (B.1.1.529) as well as other SARS-related coronaviruses. We delineate the structural basis of this relatively escape-resistant epitope that extends from one end of the receptor binding site (RBS) into the highly conserved CR3022 site. ADG20 can then benefit from high potency through direct competition with ACE2 in the more variable RBS and interaction with the more highly conserved CR3022 site. Importantly, antibodies that are able to target this site generally neutralize a broad range of VOCs, albeit with reduced potency against Omicron. Thus, this conserved and vulnerable site can be exploited for the design of universal vaccines and therapeutic antibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, based on the ancestral virus strain (1, 2), confer protective immunity and greatly decrease the incidence of infection, disease severity, and hospitalization from COVID-19. Many SARS-CoV-2 variants have emerged, and the designated variants of concern (VOCs), especially the recent Omicron variants, as well as some variants of interest, are much more resistant to neutralizing antibody (nAb) responses induced by current vaccines (3–8). A vaccine that is highly protective against current SARS-CoV-2 VOCs could potentially provide broader protection against future emerging variants and possibly other sarbecoviruses. However, neutralizing potency and breadth are often somewhat mutually exclusive; the most highly potent nAbs target the ACE2 receptor binding site (RBS) of the spike (S) protein, but most SARS-CoV-2 VOCs have mutations in the RBS that reduce nAb binding and neutralization. Broad binding antibodies, such CR3022, that target other epitopes on the receptor binding domain (RBD) usually have lower neutralization potency (9). Here, we identify a site of vulnerability on the RBD of the SARS-CoV-2 S protein that is targeted by a few diverse antibodies. Importantly, such antibodies, as exemplified by ADG20, compete with receptor binding, exhibit high neutralizing potency and show broad activity to VOCs, including Omicron, to a conserved region that is present also on other SARS-related coronaviruses (CoVs) including SARS-CoV-1, WIV1, and SHC014.     

Investigating COVID-19 Vaccine Impact on the Risk of Hospitalisation through the Analysis of National Surveillance Data Collected in Belgium

The national vaccination campaign against SARS-CoV-2 started in January 2021 in Belgium. In the present study, we aimed to use national hospitalisation surveillance data to investigate the recent evolution of vaccine impact on the risk of COVID-19 hospitalisation. We analysed aggregated data from 27,608 COVID-19 patients hospitalised between October 2021 and February 2022, stratified by age category and vaccination status. For each period, vaccination status, and age group, we estimated risk ratios (RR) corresponding to the ratio between the probability of being hospitalised following SARS-CoV-2 infection if belonging to the vaccinated population and the same probability if belonging to the unvaccinated population. In October 2021, a relatively high RR was estimated for vaccinated people > 75 years old, possibly reflecting waning immunity within this group, which was vaccinated early in 2021 and invited to receive the booster vaccination at that time. In January 2022, a RR increase was observed in all age categories coinciding with the dominance of the Omicron variant. Despite the absence of control for factors like comorbidities, previous infections, or time since the last administered vaccine, we showed that such real-time aggregated data make it possible to approximate trends in vaccine impact over time.     

Enhanced national surveillance of severe acute respiratory infections (SARI) within COVID-19 surveillance,Slovenia, weeks 13 to 37 2021

We monitored trends of severe COVID-19 morbidity in Slovenia during weeks 13 to 37 2021. National weekly rates of severe acute respiratory infections (SARI) cases testing positive for SARS-CoV-2 at admission in all hospitals varied between 0.2 and 16.3 cases per 100,000 population. Of those without previous COVID-19 diagnosis, SARI COVID-19 admission rates ranged between 0.3 and 17.5 per 100,000 unvaccinated, and 0.0 and 7.3 per 100,000 fully vaccinated individuals. National SARI COVID-19 surveillance is essential in informing COVID-19 response.     

Clinical Severity of SARS-CoV-2 Omicron Variant Compared with Delta among Hospitalized COVID-19 Patients in Belgium during Autumn and Winter Season 2021–2022

This retrospective multi-center matched cohort study assessed the risk for severe COVID-19 (combination of severity indicators), intensive care unit (ICU) admission, and in-hospital mortality in hospitalized patients when infected with the Omicron variant compared to when infected with the Delta variant. The study is based on a causal framework using individually-linked data from national COVID-19 registries. The study population consisted of 954 COVID-19 patients (of which, 445 were infected with Omicron) above 18 years old admitted to a Belgian hospital during the autumn and winter season 2021–2022, and with available viral genomic data. Patients were matched based on the hospital, whereas other possible confounders (demographics, comorbidities, vaccination status, socio-economic status, and ICU occupancy) were adjusted for by using a multivariable logistic regression analysis. The estimated standardized risk for severe COVID-19 and ICU admission in hospitalized patients was significantly lower (RR = 0.63; 95% CI (0.30; 0.97) and RR = 0.56; 95% CI (0.14; 0.99), respectively) when infected with the Omicron variant, whereas in-hospital mortality was not significantly different according to the SARS-CoV-2 variant (RR = 0.78, 95% CI (0.28–1.29)). This study demonstrates the added value of integrated genomic and clinical surveillance to recognize the multifactorial nature of COVID-19 pathogenesis.     

COVID-19 Mortality and Social Inequalities: Epidemiological analysis of the emergence and disappearance of the SARS-CoV-2 Kappa variant within a region of British Columbia,Canada

BackgroundThe Kappa variant is designated as a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of interest (VOI). We identified 195 Kappa variant cases in a region of British Columbia, Canada—the largest published cluster in North America.ObjectivesTo describe the epidemiology of the Kappa variant in relation to other circulating SARS-CoV-2 variants of concern (VOC) in the region to determine if the epidemiology of the Kappa variant supports a VOI or VOC status.MethodsClinical specimens testing positive for SARS-CoV-2 collected between March 10 and May 2, 2021, were screened for the detection of known circulating VOCs; approximately 50% of specimens were subsequently selected for whole genome sequencing (WGS). Epidemiological analysis was performed comparing the characteristics of Kappa cases to the main circulating variants in the region (Alpha and Gamma) and to non-VOC/VOI cases.ResultsA total of 2,079 coronavirus disease 2019 (COVID-19) cases were reported in the region during the study period, of which 54% were selected for WGS. The 1,131 sequenced cases were categorized into Kappa, Alpha, Gamma and non-VOC/VOI. While Alpha and Gamma cases were found to have a significantly higher attack rate among household contacts compared to non-VOI/VOC cases, Kappa was not.ConclusionEpidemiological analysis supports the designation of Kappa as a VOI and not a VOC. The Alpha and Gamma variants were found to be more transmissible, explaining their subsequent dominance in the region and the rapid disappearance of the Kappa variant. Variant surveillance strategies should focus on both detection of established VOCs and detection of potential new VOCs.     

Genomic Diversity of SARS-CoV-2 Omicron Variant in South American Countries

Genomic surveillance of SARS-CoV-2 is one of the tools that provide genomic information on circulating variants. Given the recent emergence of the Omicron (B.1.1.529) variant, this tool has provided data about this lineage’s genomic and epidemiological characteristics. However, in South America, this variant’s arrival and genomic diversity are scarcely known. Therefore, this study determined the genomic diversity and phylogenetic relationships of 21,615 Omicron genomes available in public databases. We found that in South America, BA.1 (n = 15,449, 71%) and BA.1.1 (n = 6257, 29%) are the dominant sublineages, with several mutations that favor transmission and antibody evasion. In addition, these lineages showed cryptic transmission arriving on the continent in late September 2021. This event may have contributed to the dispersal of Omicron sublineages and the acquisition of new mutations. Considering the genomic and epidemiological characteristics of these lineages, especially those with a high number of mutations in their genome, it is important to conduct studies and surveillance on the dynamics of these lineages to identify the mechanisms of mutation acquisition and their impact on public health.