Inhibition Mechanism of SARS-CoV-2 Infection by a Cholesterol Derivative, Nat-20(S)-yne.

The coronavirus disease 2019 (COVID-19) is caused by the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19, with the recurrent epidemics of new variants of SARS-CoV-2, remains a global public health problem, and new antivirals are still required. Some cholesterol derivatives, such as 25-hydroxycholesterol, are known to have antiviral activity against a wide range of enveloped and non-enveloped viruses, including SARS-CoV-2. At the entry step of SARS-CoV-2 infection, the viral envelope fuses with the host membrane dependent of viral spike (S) glycoproteins. From the screening of cholesterol derivatives, we found a new compound 26,27-dinorcholest-5-en-24-yne-3ß,20-diol (Nat-20(S)-yne) that inhibited the SARS-CoV-2 S protein-dependent membrane fusion in a syncytium formation assay. Nat-20(S)-yne exhibited the inhibitory activities of SARS-CoV-2 pseudovirus entry and intact SARS-CoV-2 infection in a dose-dependent manner. Among the variants of SARS-CoV-2, inhibition of infection by Nat-20(S)-yne was stronger in delta and Wuhan strains, which predominantly invade into cells via fusion at the plasma membrane, than in omicron strains. The interaction between receptor-binding domain of S proteins and host receptor ACE2 was not affected by Nat-20(S)-yne. Unlike 25-hydroxycholesterol, which regulates various steps of cholesterol metabolism, Nat-20(S)-yne inhibited only de novo cholesterol biosynthesis. As a result, plasma membrane cholesterol content was substantially decreased in Nat-20(S)-yne-treated cells, leading to inhibition of SARS-CoV-2 infection. Nat-20(S)-yne having a new mechanism of action may be a potential therapeutic candidate for COVID-19.

Drug repurposing: identification of SARS-CoV-2 potential inhibitors by virtual screening and pharmacokinetics strategies.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic caused global health, economic, and population loss. Variants of the coronavirus contributed to the severity of the disease and persistent rise in infections. This study aimed to identify potential drug candidates from fifteen approved antiviral drugs against SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike protein (6M0J) using virtual screening and pharmacokinetics to gain insights into COVID-19 therapeutics. METHODOLOGY: We employed drug repurposing approach to analyze binding performance of fifteen clinically approved antiviral drugs against the main protease of SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike proteins bound to ACE-2 receptor (6M0J), to provide an insight into the therapeutics of COVID-19. AutoDock Vina was used for docking studies. The binding affinities were calculated, and 2-3D structures of protein-ligand interactions were drawn. RESULTS: Rutin, hesperidin, and nelfinavir are clinically approved antiviral drugs with high binding affinity to proteins 6LU7, 5B6O, and 6M0J. These ligands have excellent pharmacokinetics, ensuring efficient absorption, metabolism, excretion, and digestibility. Hesperidin showed the most potent interaction with spike protein 6M0J, forming four H-bonds. Nelfinavir had a high human intestinal absorption (HIA) score of 0.93, indicating maximum absorption in the body and promising interactions with 6LU7. CONCLUSIONS: Our results indicated that rutin, hesperidin, and nelfinavir had the highest binding results against the proposed drug targets. The computational approach effectively identified SARS-CoV-2 inhibitors. COVID-19 is still a recurrent threat globally and predictive analysis using natural compounds might serve as a starting point for new drug development against SARS-CoV-2 and related viruses.

Lessons learned from the COVID-19 pandemic: The importance of physician leadership in responding to rural community ecosystem disruptions.

INTRODUCTION: The COVID-19 pandemic presented an unprecedented challenge for rural family physicians. The lessons learned over the course of 2 years have potential to help guide responses to future ecosystem disruption. This qualitative study aims to explore the leadership experiences of rural Canadian family physicians during the COVID-19 pandemic as both local care providers and community health leaders and to identify potential supports and barriers to physician leadership. METHODS: Semi-structured, virtual, qualitative interviews were completed with participants from rural communities in Canada from December 2021 to February 2022 inclusive. Participant recruitment involved identifying seed contacts and conducting snowball sampling. Participants were asked about their experiences during the COVID-19 pandemic, including the role of physician leadership in building community resilience. Data collection was completed on theoretical saturation. Data were thematically analysed using NVivo 12. RESULTS: Sixty-four participants took part from 22 rural communities in 4 provinces. Four key factors were identified that supported physician leadership towards rural resilience during ecosystem disruption: (1) continuity of care, (2) team-based care models, (3) physician well-being and (4) openness to innovative care models. CONCLUSION: Healthcare policy and practice transformation should prioritise developing opportunities to strengthen physician leadership, particularly in rural areas that will be adversely affected by ecosystem disruption. INTRODUCTION: La pandémie de COVID-19 a représenté un défi sans précédent pour les médecins de famille en milieu rural. Les leçons tirées au cours des deux années écoulées peuvent aider à orienter les réponses aux futures perturbations de l'écosystème. Cette étude qualitative vise à explorer les expériences de leadership des médecins de famille ruraux canadiens pendant la pandémie de COVID-19, en tant que prestataires de soins locaux et chefs de file de la santé communautaire, et à identifier les soutiens et les obstacles potentiels au leadership des médecins. MTHODES: Des entretiens qualitatifs virtuels semi-structurés ont été réalisés avec des participants issus de communautés rurales du Canada entre décembre 2021 et février 2022 inclus. Le recrutement des participants a consisté à identifier des contacts de base et à procéder à un échantillonnage boule de neige. Les participants ont été interrogés sur leurs expériences durant la pandémie de COVID-19, notamment sur le rôle du leadership des médecins dans le renforcement de la résilience des communautés. La collecte des données s'est achevée après saturation théorique. Les données ont été analysées thématiquement à l'aide de NVivo 12. RSULTATS: Soixante-quatre participants provenant de 22 communautés rurales de quatre provinces ont pris part à l'étude. Quatre facteurs clés ont été identifiés pour soutenir le leadership des médecins en faveur de la résilience rurale en cas de perturbation de l'écosystème: (1) la continuité des soins, (2) les modèles de soins en équipe, (3) le bien-être des médecins et (4) l'ouverture à des modèles de soins novateurs. CONCLUSION: La politique de santé et la transformation des pratiques devraient donner la priorité au développement d'opportunités pour renforcer le leadership des médecins, en particulier dans les zones rurales qui seront négativement affectées par la perturbation de l'écosystème.

Psychotropic Medication Prescribing for Children and Adolescents After the Onset of the COVID-19 Pandemic.

Importance: Numerous studies have provided evidence for the negative associations of the COVID-19 pandemic with mental health, but data on the use of psychotropic medication in children and adolescents after the onset of the COVID-19 pandemic are lacking. Objective: To assess the rates and trends of psychotropic medication prescribing before and over the 2 years after the onset of the COVID-19 pandemic in children and adolescents in France. Design, Setting, and Participants: This cross-sectional study used nationwide interrupted time-series analysis of outpatient drug dispensing data from the IQVIA X-ponent database. All 8 839 143 psychotropic medication prescriptions dispensed to children (6 to 11 years of age) and adolescents (12 to 17 years of age) between January 2016 and May 2022 in France were retrieved and analyzed. Exposure: Onset of COVID-19 pandemic. Main outcomes and Measures: Monthly rates of psychotropic medication prescriptions per 1000 children and adolescents were analyzed using a quasi-Poisson regression before and after the pandemic onset (March 2020), and percentage changes in rates and trends were assessed. After the pandemic onset, rate ratios (RRs) were calculated between estimated and expected monthly prescription rates. Analyses were stratified by psychotropic medication class (antipsychotic, anxiolytic, hypnotic and sedative, antidepressant, and psychostimulant) and age group (children, adolescents). Results: In total, 8 839 143 psychotropic medication prescriptions were analyzed, 5 884 819 [66.6%] for adolescents and 2 954 324 [33.4%] for children. In January 2016, the estimated rate of monthly psychotropic medication prescriptions was 9.9 per 1000 children and adolescents, with the prepandemic rate increasing by 0.4% per month (95% CI, 0.3%-0.4%). In March 2020, the monthly prescription rate dropped by 11.5% (95% CI, -17.7% to -4.9%). During the 2 years following the pandemic onset, the trend changed significantly, and the prescription rate increased by 1.3% per month (95% CI, 1.2%-1.5%), reaching 16.1 per 1000 children and adolescents in May 2022. Monthly rates of psychotropic medication prescriptions exceeded the expected rates by 11% (RR, 1.11 [95% CI, 1.08-1.14]). Increases in prescribing trends were observed for all psychotropic medication classes after the pandemic onset but were substantial for anxiolytics, hypnotics and sedatives, and antidepressants. Prescription rates rose above those expected for all psychotropic medication classes except psychostimulants (RR, 1.12 [95% CI, 1.09-1.15] in adolescents and 1.06 [95% CI, 1.05-1.07] in children for antipsychotics; RR, 1.30 [95% CI, 1.25-1.35] in adolescents and 1.11 [95% CI, 1.09-1.12] in children for anxiolytics; RR, 2.50 [95% CI, 2.23-2.77] in adolescents and 1.40 [95% CI, 1.30-1.50] in children for hypnotics and sedatives; RR, 1.38 [95% CI, 1.29-1.47] in adolescents and 1.23 [95% CI, 1.20-1.25] in children for antidepressants; and RR, 0.97 [95% CI, 0.95-0.98] in adolescents and 1.02 [95% CI, 1.00-1.04] in children for psychostimulants). Changes were more pronounced among adolescents than children. Conclusions and Relevance: These findings suggest that prescribing of psychotropic medications for children and adolescents in France significantly and persistently increased after the COVID-19 pandemic onset. Future research should identify underlying determinants to improve psychological trajectories in young people.

Long-Term Taste and Smell Outcomes After COVID-19.

Importance: Self-report surveys suggest that long-lasting taste deficits may occur after SARS-CoV-2 infection, influencing nutrition, safety, and quality of life. However, self-reports of taste dysfunction are inaccurate, commonly reflecting deficits due to olfactory not taste system pathology; hence, quantitative testing is needed to verify the association of post-COVID-19 condition with taste function. Objective: To use well-validated self-administered psychophysical tests to investigate the association of COVID-19 with long-term outcomes in taste and smell function. Design, Setting, and Participants: This nationwide cross-sectional study included individuals with and without a prior history of COVID-19 recruited from February 2020 to August 2023 from a social media website (Reddit) and bulletin board advertisements. In the COVID-19 cohort, there was a mean of 395 days (95% CI, 363-425 days) between diagnosis and testing. Exposure: History of COVID-19. Main Outcomes and Measures: The 53-item Waterless Empirical Taste Test (WETT) and 40-item University of Pennsylvania Smell Identification Test (UPSIT) were used to assess taste and smell function. Total WETT and UPSIT scores and WETT subtest scores of sucrose, citric acid, sodium chloride, caffeine, and monosodium glutamate were assessed for groups with and without a COVID-19 history. The association of COVID-19 with taste and smell outcomes was assessed using analysis of covariance, χ2, and Fisher exact probability tests. Results: Tests were completed by 340 individuals with prior COVID-19 (128 males [37.6%] and 212 females [62.4%]; mean [SD] age, 39.04 [14.35] years) and 434 individuals with no such history (154 males [35.5%] and 280 females [64.5%]; mean (SD) age, 39.99 [15.61] years). Taste scores did not differ between individuals with and without previous COVID-19 (total WETT age- and sex-adjusted mean score, 33.41 [95% CI, 32.37-34.45] vs 33.46 [95% CI, 32.54-34.38]; P = .94). In contrast, UPSIT scores were lower in the group with previous COVID-19 than the group without previous COVID-19 (mean score, 34.39 [95% CI, 33.86-34.92] vs 35.86 [95% CI, 35.39-36.33]; P < .001]); 103 individuals with prior COVID-19 (30.3%) and 91 individuals without prior COVID-19 (21.0%) had some degree of dysfunction (odds ratio, 1.64 [95% CI, 1.18-2.27]). The SARS-CoV-2 variant present at the time of infection was associated with smell outcomes; individuals with original untyped and Alpha variant infections exhibited more loss than those with other variant infections; for example, total to severe loss occurred in 10 of 42 individuals with Alpha variant infections (23.8%) and 7 of 52 individuals with original variant infections (13.5%) compared with 12 of 434 individuals with no COVID-19 history (2.8%) (P < .001 for all). Conclusions and Relevance: In this study, taste dysfunction as measured objectively was absent 1 year after exposure to COVID-19 while some smell loss remained in nearly one-third of individuals with this exposure, likely explaining taste complaints of many individuals with post-COVID-19 condition. Infection with earlier untyped and Alpha variants was associated with the greatest degree of smell loss.

Patients hospitalized with active tuberculosis and Covid-19 coinfection: A matched case-control from the Brazilian Covid-19 Registry.

Although control of Covid-19 has improved, the virus continues to cause infections, such as tuberculosis, that is still endemic in many countries, representing a scenario of coinfection. To compare Covid-19 clinical manifestations and outcomes between patients with active tuberculosis infection and matched controls. This is a matched case-control study based on data from the Brazilian Covid-19 Registry, in hospitalized patients aged 18 or over with laboratory confirmed Covid-19 from March 1, 2020, to March 31, 2022. Cases were patients with tuberculosis and controls were Covid-19 patients without tuberculosis. From 13,636 Covid-19, 36 also had active tuberculosis (0.0026%). Pulmonary fibrosis (5.6% vs 0.0%), illicit drug abuse (30.6% vs 3.0%), alcoholism (33.3% vs 11.9%) and smoking (50.0% vs 9.7%) were more common among patients with tuberculosis. They also had a higher frequency of nausea and vomiting (25.0% vs 10.4%). There were no significant differences in in-hospital mortality, mechanical ventilation, need for dialysis and ICU stay. Patients with TB infection presented a higher frequency of pulmonary fibrosis, abuse of illicit drugs, alcoholism, current smoking, symptoms of nausea and vomiting. The outcomes were similar between them.

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Objective: To construct a deep learning-based target detection method to help radiologists perform rapid diagnosis of lesions in the CT images of patients with novel coronavirus pneumonia (NCP) by restoring detailed information and mining local information. Methods: We present a deep learning approach that integrates detail upsampling and attention guidance. A linear upsampling algorithm based on bicubic interpolation algorithm was adopted to improve the restoration of detailed information within feature maps during the upsampling phase. Additionally, a visual attention mechanism based on vertical and horizontal spatial dimensions embedded in the feature extraction module to enhance the capability of the object detection algorithm to represent key information related to NCP lesions. Results: Experimental results on the NCP dataset showed that the detection method based on the detail upsampling algorithm improved the recall rate by 1.07% compared with the baseline model, with the AP50 reaching 85.14%. After embedding the attention mechanism in the feature extraction module, 86.13% AP50, 73.92% recall, and 90.37% accuracy were achieved, which were better than those of the popular object detection models. Conclusion: The feature information mining of CT images based on deep learning can further improve the lesion detection ability. The proposed approach helps radiologists rapidly identify NCP lesions on CT images and provides an important clinical basis for early intervention and high-intensity monitoring of NCP patients.

SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure.

SARS-CoV-2 has been shown to cause wide-ranging ocular abnormalities and vision impairment in COVID-19 patients. However, there is limited understanding of SARS-CoV-2 in ocular transmission, tropism, and associated pathologies. The presence of viral RNA in corneal/conjunctival tissue and tears, along with the evidence of viral entry receptors on the ocular surface, has led to speculation that the eye may serve as a potential route of SARS-CoV-2 transmission. Here, we investigated the interaction of SARS-CoV-2 with cells lining the blood-retinal barrier (BRB) and the role of the eye in its transmission and tropism. The results from our study suggest that SARS-CoV-2 ocular exposure does not cause lung infection and moribund illness in K18-hACE2 mice despite the extended presence of viral remnants in various ocular tissues. In contrast, intranasal exposure not only resulted in SARS-CoV-2 spike (S) protein presence in different ocular tissues but also induces a hyperinflammatory immune response in the retina. Additionally, the long-term exposure to viral S-protein caused microaneurysm, retinal pigmented epithelium (RPE) mottling, retinal atrophy, and vein occlusion in mouse eyes. Notably, cells lining the BRB, the outer barrier, RPE, and the inner barrier, retinal vascular endothelium, were highly permissive to SARS-CoV-2 replication. Unexpectedly, primary human corneal epithelial cells were comparatively resistant to SARS-CoV-2 infection. The cells lining the BRB showed induced expression of viral entry receptors and increased susceptibility towards SARS-CoV-2-induced cell death. Furthermore, hyperglycemic conditions enhanced the viral entry receptor expression, infectivity, and susceptibility of SARS-CoV-2-induced cell death in the BRB cells, confirming the reported heightened pathological manifestations in comorbid populations. Collectively, our study provides the first evidence of SARS-CoV-2 ocular tropism via cells lining the BRB and that the virus can infect the retina via systemic permeation and induce retinal inflammation.

Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses.

Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then slide over and enter via ACE2. SARS-CoV-2 SP attaches particularly tightly to the trillions of red blood cells (RBCs), platelets and endothelial cells in the human body, each cell very densely coated with sialic acid surface molecules but having no ACE2 or minimal ACE2. These interlaced attachments trigger the blood cell aggregation, microvascular occlusion and vascular damage that underlie the hypoxia, blood clotting and related morbidities of severe COVID-19. Notably, the two human betacoronaviruses that express a sialic acid-cleaving enzyme are benign, while the other three-SARS, SARS-CoV-2 and MERS-are virulent. RBC aggregation experimentally induced in several animal species using an injected polysaccharide caused most of the same morbidities of severe COVID-19. This glycan biochemistry is key to disentangling controversies that have arisen over the efficacy of certain generic COVID-19 treatment agents and the safety of SP-based COVID-19 vaccines. More broadly, disregard for the active physiological role of RBCs yields unreliable or erroneous reporting of pharmacokinetic parameters as routinely obtained for most drugs and other bioactive agents using detection in plasma, with whole-blood levels being up to 30-fold higher. Appreciation of the active role of RBCs can elucidate the microvascular underpinnings of other health conditions, including cardiovascular disease, and therapeutic opportunities to address them.

Bioinformatics and system biology approaches to determine the connection of SARS-CoV-2 infection and intrahepatic cholangiocarcinoma.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals worldwide, which poses a severe threat to human health. COVID-19 is a systemic ailment affecting various tissues and organs, including the lungs and liver. Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver cancer, and cancer patients are particularly at high risk of SARS-CoV-2 infection. Nonetheless, few studies have investigated the impact of COVID-19 on ICC patients. METHODS: With the methods of systems biology and bioinformatics, this study explored the link between COVID-19 and ICC, and searched for potential therapeutic drugs. RESULTS: This study identified a total of 70 common differentially expressed genes (DEGs) shared by both diseases, shedding light on their shared functionalities. Enrichment analysis pinpointed metabolism and immunity as the primary areas influenced by these common genes. Subsequently, through protein-protein interaction (PPI) network analysis, we identified SCD, ACSL5, ACAT2, HSD17B4, ALDOA, ACSS1, ACADSB, CYP51A1, PSAT1, and HKDC1 as hub genes. Additionally, 44 transcription factors (TFs) and 112 microRNAs (miRNAs) were forecasted to regulate the hub genes. Most importantly, several drug candidates (Periodate-oxidized adenosine, Desipramine, Quercetin, Perfluoroheptanoic acid, Tetrandrine, Pentadecafluorooctanoic acid, Benzo[a]pyrene, SARIN, Dorzolamide, 8-Bromo-cAMP) may prove effective in treating ICC and COVID-19. CONCLUSION: This study is expected to provide valuable references and potential drugs for future research and treatment of COVID-19 and ICC.

A positive selection at binding site 501 in the B.1 lineage might have triggered the highly infectious sub-lineages of SARS-CoV-2.

The descendants of the B lineage are the most predominant variants among the SARS-CoV-2 virus due to the incorporation of new mutations augmenting the infectivity of the virus. There is a substantial increase in the transition transversion bias, nucleotide diversity and purifying selection on the spike protein in the descendants of the B lineage of the SARS-CoV-2 virus on a temporal scale. A strong bias for C-to-U substitutions is found in the genes encoding spike protein in this lineage. The positive selection has operated on the spike gene of B lineages and its sub-lineages. The B.1 lineage has undergone positive selection on site 501 of the receptor binding domain ultimately reflected in a key substitution N501Y in its three descendant lineages namely B.1.1.7, B.1.351 and P.1. The intensity of purifying selection on the multiple sites of the spike gene has increased substantially in the sub-lineages of B.1 in a timescale. The binding site 501 on the spike protein in B lineage is found to coevolve with other amino acid sites. This study sheds light on the evolutionary trajectory of the B lineage into highly infectious descendants in the recent past under the influence of positive and purifying selection exerted by natural immunity and vaccination of the host.

Review: N1-methyl-pseudouridine (m1Ψ): Friend or foe of cancer?

Due to the health emergency created by SARS-CoV-2, the virus that causes the COVID-19 disease, the rapid implementation of a new vaccine technology was necessary. mRNA vaccines, being one of the cutting-edge new technologies, attracted significant interest and offered a lot of hope. The potential of these vaccines in preventing admission to hospitals and serious illness in people with comorbidities has recently been called into question due to the vaccines' rapidly waning immunity. Mounting evidence indicates that these vaccines, like many others, do not generate sterilizing immunity, leaving people vulnerable to recurrent infections. Additionally, it has been discovered that the mRNA vaccines inhibit essential immunological pathways, thus impairing early interferon signaling. Within the framework of COVID-19 vaccination, this inhibition ensures an appropriate spike protein synthesis and a reduced immune activation. Evidence is provided that adding 100 % of N1-methyl-pseudouridine (m1Ψ) to the mRNA vaccine in a melanoma model stimulated cancer growth and metastasis, while non-modified mRNA vaccines induced opposite results, thus suggesting that COVID-19 mRNA vaccines could aid cancer development. Based on this compelling evidence, we suggest that future clinical trials for cancers or infectious diseases should not use mRNA vaccines with a 100 % m1Ψ modification, but rather ones with the lower percentage of m1Ψ modification to avoid immune suppression.

Neutralization of EG.5, EG.5.1, BA.2.86, and JN.1 by antisera from dimeric receptor-binding domain subunit vaccines and 41 human monoclonal antibodies.

BACKGROUND: The recently circulating Omicron variants BA.2.86 and JN.1 were identified with more than 30 amino acid changes on the spike protein compared to BA.2 or XBB.1.5. This study aimed to comprehensively assess the immune escape potential of BA.2.86, JN.1, EG.5, and EG.5.1. METHODS: We collected human and murine sera to evaluate serological neutralization activities. The participants received three doses of coronavirus disease 2019 (COVID-19) vaccines or a booster dose of the ZF2022-A vaccine (Delta-BA.5 receptor-binding domain [RBD]-heterodimer immunogen) or experienced a breakthrough infection (BTI). The ZF2202-A vaccine is under clinical trial study (ClinicalTrials.gov: NCT05850507). BALB/c mice were vaccinated with a panel of severe acute respiratory syndrome coronavirus 2 RBD-dimer proteins. The antibody evasion properties of these variants were analyzed with 41 representative human monoclonal antibodies targeting the eight RBD epitopes. FINDINGS: We found that BA.2.86 had less neutralization evasion than EG.5 and EG.5.1 in humans. The ZF2202-A booster induced significantly higher neutralizing titers than BTI. Furthermore, BA.2.86 and JN.1 exhibited stronger antibody evasion than EG.5 and EG.5.1 on RBD-4 and RBD-5 epitopes. Compared to BA.2.86, JN.1 further lost the ability to bind to several RBD-1 monoclonal antibodies and displayed further immune escape. CONCLUSIONS: Our data showed that the currently dominating sub-variant, JN.1, showed increased immune evasion compared to BA.2.86 and EG.5.1, which is highly concerning. This study provides a timely risk assessment of the interested sub-variants and the basis for updating COVID-19 vaccines. FUNDING: This work was funded by the National Key R&D Program of China, the National Natural Science Foundation of China, the Beijing Life Science Academy, the Bill & Melinda Gates Foundation, and the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation (CPSF).

Antibiotics daptomycin interacts with S protein of SARS-CoV-2 to promote cell invasion of Omicron (B1.1.529) pseudovirus.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed enormous challenges to global public health. The use of antibiotics has greatly increased during the SARS-CoV-2 epidemic owing to the presence of bacterial co-infection and secondary bacterial infections. The antibiotics daptomycin (DAP) is widely used in the treatment of infectious diseases caused by gram-positive bacteria owing to its highly efficient antibacterial activity. It is pivotal to study the antibiotics usage options for patients of coronavirus infectious disease (COVID-19) with pneumonia those need admission to receive antibiotics treatment for bacterial co-infection in managing COVID-19 disease. Herein, we have revealed the interactions of DAP with the S protein of SARS-CoV-2 and the variant Omicron (B1.1.529) using the molecular docking approach and Omicron (B1.1.529) pseudovirus (PsV) mimic invasion. Molecular docking analysis shows that DAP has a certain degree of binding ability to the S protein of SARS-CoV-2 and several derived virus variants, and co-incubation of 1-100 µM DAP with cells promotes the entry of the PsV into human angiotensin-converting enzyme 2 (hACE2)-expressing HEK-293T cells (HEK-293T-hACE2), and this effect is related to the concentration of extracellular calcium ions (Ca2+). The PsV invasion rate in the HEK-293T-hACE2 cells concurrently with DAP incubation was 1.7 times of PsV infection alone. In general, our findings demonstrate that DAP promotes the infection of PsV into cells, which provides certain reference of antibiotics selection and usage optimization for clinicians to treat bacterial coinfection or secondary infection during SARS-CoV-2 infection.

Patterns of Non-influenza Respiratory Viruses Among Severe Acute Respiratory Infection Cases in Burkina Faso: A Surveillance Study.

BACKGROUND: Although influenza viruses cause only one-fifth of severe acute respiratory infections (SARI) in Burkina Faso, the other viral causes of SARI remain poorly investigated to inform clinical and preventive decision making. METHODS: Between 2016 and 2019, we prospectively enrolled inpatients meeting the World Health Organization (WHO) case definition of SARI in Burkina Faso. Results of viral etiologies among inpatients tested negative for influenza using the Fast Track Diagnostics Respiratory Kits (FTD-33) were reported. RESULTS: Of 1541 specimens tested, at least one respiratory virus was detected in 76.1% of the 1231 specimens negative for influenza virus. Human rhinoviruses (hRVs) were the most detected pathogens (476; 38.7%), followed by human adenoviruses (hAdV) (17.1%, 210/1231), human respiratory syncytial virus (hRSV) (15.4%, 189/1231), enterovirus (EnV) (11.2%, 138/1231), human bocavirus (hBoV) (7.9%, 97/1231), parainfluenza 3 (hPIV3) (6.1%, 75/1231), human metapneumovirus (hMPV) (6.0%,74/1321), parainfluenza 4 (hPIV4) (4.1%, 51/1231), human coronavirus OC43 (hCoV-OC43) (3.4%, 42/1231), human coronavirus HKU1(hCoV-HKU1) (2.7%, 33/1231), human coronavirus NL63 (hCoV-NL63) (2.5%, 31/1231), parainfluenza 1 (hPIV1) (2.0%, 25/1231), parainfluenza 2 (hPIV2) (1.8%, 22/1231), human parechovirus (PeV) (1.1%, 14/1231), and human coronavirus 229E (hCoV-229E) (0.9%, 11/1231). Among SARI cases, infants aged 1-4 years were mostly affected (50.7%; 622/1231), followed by those <1 year of age (35.7%; 438/1231). Most detected pathogens had year-long circulation patterns, with seasonal peaks mainly observed during the cold and dry seasons. CONCLUSION: Several non-influenza viruses are cause of SARI in Burkina Faso. The integration of the most common pathogens into the routine influenza surveillance system might be beneficial.

Conserved structures and dynamics in 5'-proximal regions of Betacoronavirus RNA genomes.

Betacoronaviruses are a genus within the Coronaviridae family of RNA viruses. They are capable of infecting vertebrates and causing epidemics as well as global pandemics in humans. Mitigating the threat posed by Betacoronaviruses requires an understanding of their molecular diversity. The development of novel antivirals hinges on understanding the key regulatory elements within the viral RNA genomes, in particular the 5'-proximal region, which is pivotal for viral protein synthesis. Using a combination of cryo-electron microscopy, atomic force microscopy, chemical probing, and computational modeling, we determined the structures of 5'-proximal regions in RNA genomes of Betacoronaviruses from four subgenera: OC43-CoV, SARS-CoV-2, MERS-CoV, and Rousettus bat-CoV. We obtained cryo-electron microscopy maps and determined atomic-resolution models for the stem-loop-5 (SL5) region at the translation start site and found that despite low sequence similarity and variable length of the helical elements it exhibits a remarkable structural conservation. Atomic force microscopy imaging revealed a common domain organization and a dynamic arrangement of structural elements connected with flexible linkers across all four Betacoronavirus subgenera. Together, these results reveal common features of a critical regulatory region shared between different Betacoronavirus RNA genomes, which may allow targeting of these RNAs by broad-spectrum antiviral therapeutics.

Otologic disease trends in Japan post-COVID-19 outbreak: A retrospective time-series analysis.

OBJECTIVE: To evaluate the potential impact of coronavirus disease 2019 (COVID-19) and vaccinations on otologic diseases, including facial nerve paralysis (including Ramsay Hunt syndrome), vestibular neuritis, sudden sensorineural hearing loss, and Meniere's disease. METHODS: In this retrospective study, we conducted a time-series analysis employing a causal impact algorithm on a large-scale inpatient database in Japan. We compared the actual number of hospitalized patients with otologic diseases to two predictions: one without any covariates and another with a covariate accounting for the reduction in the number of hospitalized patients due to lockdown measures. Additionally, we performed Granger causality tests to ensure the robustness of our findings. RESULTS: No significant increase was noted in the number of hospitalized patients with otologic diseases following the onset of the COVID-19 pandemic in the causal impact analysis. Similarly, no notable surge was observed in hospitalizations for these diseases following the introduction of the COVID-19 vaccine. The Granger causality tests results aligned with the causal impact analysis findings. CONCLUSION: Our findings indicate that COVID-19 and vaccinations had minimal discernible effects on hospitalization of patients with otologic diseases, suggesting that otologic diseases may not be significantly impacted by COVID-19 and vaccinations, which could have implications for public health policies and the allocation of healthcare resources during a pandemic. Further research and monitoring of long-term effects are warranted to validate these findings and guide healthcare decision-making.

Regional Update, Influenza and Other Respiratory Viruses. Epidemiological Week 11 (22 March 2024)

[WEEKLY SUMMARY]. Regional Situation: Over the past four Epidemiological Weeks (EWs), the Americas region has experienced intermediate levels of Influenza-Like Illness (ILI) activity, showing a decreasing trend. Concurrently, there has been a decline in Severe Acute Respiratory Infection (SARI) activity, currently at low levels. Both ILI and SARI activities have been associated with positive cases of influenza and SARS-CoV-2. ILI activity has been notably influenced by moderate activity in North America and the Caribbean, while SARI activity has been particularly impacted by trends in North America. Regarding respiratory virus circulation, regional SARS-CoV-2 activity has decreased after an observed increase in previous weeks, although it remains moderate compared to previous epidemic waves. Additionally, an epidemic activity of influenza has been observed for this time of year, alongside a declining activity of Respiratory Syncytial Virus (RSV), which is currently at low levels. North America: Despite a slight decline in previous EWs, ILI cases have maintained medium-high levels, primarily attributed to influenza. SARI cases and respiratory virus-related hospitalizations have continued to decline. Influenza activity has remained at epidemic levels, showing a slight decrease over the past four EWs. Predominant influenza viruses during this period have been type A , with A(H1N1)pdm09 and A(H3N2) circulating concurrently, along with lesser circulation of influenza B/Victoria. RSV activity has declined over the past four EWs, maintaining moderate levels. SARS-CoV-2 activity has decreased over the same period to low levels compared to previous waves. By countries: In Canada, SARS-CoV-2 activity has significantly decreased over the past four EWs to medium-low levels. Influenza activity has remained epidemic, gradually declining, while RSV activity has also decreased to moderate levels. In Mexico, influenza circulation has fluctuated at epidemic levels over the past four EWs, with SARS-CoV-2 circulation remaining at intermediate levels compared to previous waves. In the United States, influenza activity has consistently remained above the epidemic threshold, while RSV and SARSCoV- 2 activities have decreased to low levels. ILI cases have remained stable at medium levels. Hospitalization rates for influenza, RSV, and SARS-CoV-2 have shown a downward trend over the past four EWs after reaching similar elevated levels as the previous season. Caribbean: Following a previous increase, ILI cases have markedly decreased over the past four weeks, primarily attributed to influenza. SARI cases have continued to decline, with most positive cases associated with influenza. Influenza activity has decreased over the past four EWs, reaching low circulation levels. Predominant viruses during this period have been influenza A(H1N1)pdm09, with concurrent circulation of A(H3N2) and B/Victoria to a lesser extent. RSV activity has remained low, and SARS-CoV-2 activity has also declined to low levels. By countries: Increased influenza activity has been observed in Suriname and the Cayman Islands. Elevated SARS-CoV-2 activity has been observed in Dominica, Saint Lucia, Guyana, and Saint Vincent and the Grenadines. Central America: ILI activity has remained stable at low levels, primarily attributed to influenza. SARI cases have shown a slight increase but remain at low levels, with most positive cases attributed to influenza. Influenza activity has increased to intermediate levels over the last four EWs. During this period, predominant influenza viruses have been type A(H1N1)pdm09, with concurrent circulation of A(H3N2) and to a lesser extent, B/Victoria. RSV activity has remained at low levels. SARS-CoV-2 activity has also remained at low levels. By countries: In El Salvador, SARS-CoV-2 activity has decreased over the past four EWs to low levels, while SARI activity has remained at epidemic levels. In Guatemala, an increase in ILI cases associated with influenza has been observed, reaching moderate levels, while SARI cases have remained at epidemic levels, primarily associated with influenza. In Honduras, there has been a new increase in SARI cases, reaching epidemic levels, associated with a rise in positive cases for influenza. In Nicaragua, activity for both RSV, influenza, and SARS-CoV-2 has decreased to low levels. In Panama, influenza activity has shown a pronounced increase to moderate levels over the past four EWs, while ILI and SARI cases have remained low. have continued to decline to low levels, with the majority of positive cases attributable to SARS-CoV-2 and, to a lesser extent, influenza. Influenza activity has remained at low levels over the last four EWs. During this period, predominant influenza viruses have been type A(H1N1)pdm09, with concurrent circulation of A(H3N2) and, to a lesser extent, B/Victoria. RSV activity has remained at low levels. SARS-CoV-2 activity has remained on the decline to moderate levels. By countries: In Bolivia, an increase in ILI and SARI cases has been observed, reaching levels around the epidemic threshold associated with positive cases for influenza. Influenza has shown a marked increase in activity, surpassing the elevated threshold. In Colombia, SARS-CoV-2 activity has decreased over the last four EWs to medium-low levels; SARI activity has been around the epidemic threshold during these last four EWs, with positive cases attributable to influenza and, to a lesser extent, SARS-CoV-2 and RSV. In Ecuador, SARS-CoV-2 activity has increased to medium-high levels, influenza activity has remained below the epidemic threshold, and RSV activity has remained at moderate levels over the last four EWs. SARI activity has fluctuated around the moderate threshold, with positive SARI cases attributable to influenza, SARS-CoV-2, and, to a lesser extent, RSV. In Peru, after a marked increase in SARS-CoV-2 activity in previous weeks, a decrease has been observed in the last four EWs to low levels. In Venezuela, fluctuating influenza activity has been observed below the epidemic threshold over the last four EWs. Brazil and Southern Cone: SARI and ILI activity have remained at low levels over the last four EWs, with the majority of positive cases attributable to SARS-CoV-2. Influenza activity has shown an increase over the last four EWs, reaching levels around the epidemic threshold in some countries. During this period, the predominant influenza viruses have been type A(H3N2) and A(H1N1)pdm09 followed by B/Victoria. RSV activity has remained at low levels. SARS-CoV-2 activity has remained on the decline with elevated levels. By countries: In Argentina, ILI and SARI levels have remained below the epidemic threshold. The percentage of SARS-CoV-2 positivity, although remaining at moderate levels, has shown a marked decrease over the last four EWs, and influenza activity is below the epidemic threshold. In Brazil, SARS-CoV-2 activity has remained at elevated levels, albeit decreasing, and influenza activity has shown an increase during the last four EWs, surpassing the epidemic threshold. In Chile, an increase in SARS-CoV-2 activity has been observed over the last four EWs at moderate levels, along with an increase in influenza activity, which has surpassed the epidemic threshold. ILI cases have shown a pronounced increase with epidemic levels; SARI cases have slightly surpassed the epidemic threshold, with the majority of positive cases for both ILI and SARI attributable to SARS-CoV-2 and to a lesser extent, influenza. In Paraguay, the circulation of SARS-CoV-2 has shown a decrease over the last four EWs, reaching low levels, while influenza and RSV activity have remained low. ILI and SARI activity have remained below the epidemic threshold. In Uruguay, SARI activity has continued below the epidemic threshold, albeit with a slight increase in the last four weeks, with the majority of the few positive cases attributable to SARS-CoV-2.

[RESUMEN SEMANAL]. Situación regional: Durante las últimas cuatro semanas epidemiológicas (SE) se han observado niveles intermedios en la actividad de la Enfermedad Tipo Influenza (ETI) en la región de las Américas, con una tendencia decreciente. A su vez se ha observado una disminución en la actividad de Infección Respiratoria Aguda Grave (IRAG), actualmente en niveles bajos. En ambos casos la actividad observada se ha asociado a casos positivos de influenza y SARS-CoV-2. La actividad de ETI se ha relacionado principalmente con la actividad moderada observada en Norteamérica y Caribe, mientras que la actividad de IRAG se ha visto especialmente influenciada por la actividad detectada en Norteamérica. En cuanto a la circulación de virus respiratorios, a nivel regional tras un ascenso observado en semanas previas, la actividad de SARS-CoV-2 ha disminuido, aunque que se mantiene moderada en comparación con olas epidémicas previas. Asimismo, se ha observado una actividad epidémica de influenza para esta época del año, y una actividad en descenso del Virus Respiratorio Sincitial (VRS) que se encuentra actualmente en niveles bajos. América del Norte: Los casos de ETI, tras un ligero descenso en SE previas, se han mantenido en niveles medio-altos con la mayoría de los casos atribuibles a influenza. Los casos de IRAG y hospitalizaciones asociadas a virus respiratorios se han mantenido un descenso. La actividad de influenza se ha mantenido en niveles epidémicos de circulación mostrando un ligero descenso durante las cuatro últimas SE. Durante este periodo, los virus de influenza predominantes han sido del tipo A, circulando de forma concurrente influenza A(H1N1)pdm09 e influenza A(H3N2), y con circulación en menor medida de influenza B/Victoria. La actividad del VRS ha mostrado un descenso en las últimas cuatro SE, manteniéndose en niveles moderados. La actividad del SARS-CoV-2 ha presentado un decremento en las últimas cuatro SE hasta niveles bajos en comparación con ola previas. Por países: En Canadá, la actividad del SARS-CoV-2 ha presentado un marcado descenso en las últimas cuatro SE hasta niveles mediobajos. La actividad de influenza se ha mantenido en niveles epidémicos con un descenso paulatino y la actividad del VRS ha mantenido un descenso encontrándose en niveles medios. En México, la circulación de influenza se ha mantenido fluctuante en niveles epidémicos en las cuatro últimas SE, y la circulación del SARS-CoV-2 se ha mantenido en niveles intermedios en comparación con olas previas. En Estados Unidos, la actividad de influenza se ha mantenido constante por encima del umbral epidémico y la actividad del VRS y del SARS-CoV-2 han mantenido un descenso hasta niveles bajos. Los casos de ETI se han mantenido estables en niveles medios. Las tasas de hospitalización por influenza, VRS y SARS-CoV-2 tras alcanzar niveles elevados similares a la temporada previa han presentado una tendencia a la baja en las cuatro últimas SE. Caribe: Tras el incremento observado en SE previas, los casos de ETI han mostrado un marcado descenso en las cuatro últimas semanas hasta niveles bajos. Los casos de IRAG han permanecido en descenso, siendo la mayoría de los casos positivos atribuibles a influenza. La actividad de influenza ha presentado un descenso en las últimas cuatro SE, alcanzando niveles bajos de circulación. Durante las cuatro últimas SE, los virus predominantes han sido de tipo A(H1N1)pdm09, y se ha observado circulación concurrente en menor medida de influenza tipo A(H3N2) y B/Victoria. La actividad del VRS se ha mantenido en niveles bajos. La actividad del SARS-CoV-2 ha permanecido en descenso hasta niveles bajos. Por países: Se ha observado una actividad elevada de influenza en Surinam y las Islas Caimán. Se ha observado una actividad elevada de SARS-CoV-2 en Dominica, Santa Lucia, Guyana y San Vicente y las Granadinas. América Central: La actividad de ETI se ha mantenido estable en niveles bajos con la mayoría de los casos positivos atribuibles a influenza. Los casos de IRAG han presentado un ligero incremento, aunque se mantiene en niveles bajos, siendo la mayor proporción de casos positivos atribuibles a influenza. La actividad de influenza ha presentado un incremento situándose en niveles intermedios en las cuatro últimas SE. Durante este periodo, los virus de influenza predominantes han sido de tipo A(H1N1)pdm09 con circulación concurrente de A(H3N2) y en menor medida de B/Victoria. La actividad del VRS se ha mantenido en niveles bajos. La actividad de SARS-CoV-2 se ha permanecido en niveles bajos. Por países: En El Salvador, la actividad de SARS-CoV-2 has descendido durante las cuatro últimas SE hasta niveles bajos y la actividad de IRAG se encuentra en torno a niveles epidémicos. En Guatemala, se ha observado un incremento en los casos de ETI asociados a influenza, encontrándose en niveles de actividad moderados; en cuanto a los casos de IRAG se mantienen en niveles epidémicos, siendo la mayoría asociados a su vez a influenza. En Honduras, se ha observado de nuevo un incremento en los casos de IRAG que se encuentran en niveles epidémicos, asociado a un ascenso en los casos positivos a influenza. En Nicaragua, la actividad tanto del VRS, influenza y SARS-CoV-2 ha descendido hasta niveles bajos. En Panamá, la actividad de influenza ha mostrado un pronunciado incremento hasta niveles moderados en las cuatro últimas SE, los casos de ETI e IRAG se han mantenido bajos en las cuatro últimas SE. Andina: La actividad de ETI se ha mantenido estable en niveles bajos con la mayoría de los casos positivos atribuibles a influenza. Los casos de IRAG se han mantenido en descenso con niveles bajos siendo la mayor proporción de casos positivos atribuibles a SARS-CoV- 2 e influenza. La actividad de influenza ha permanecido en niveles bajos en las cuatro últimas SE. Durante este periodo, los virus de influenza predominantes han sido de tipo A(H1N1)pdm09 con circulación concurrente de A(H3N2) y en menor medida de B/Victoria. La actividad del VRS se ha mantenido en niveles bajos. La actividad de SARS-CoV-2 se ha mantenido en descenso con niveles medios. Por países: En Bolivia, se ha observado un incremento en los casos de ETI e IRAG asociado a casos positivos a influenza y con niveles en torno al umbral epidémico. La influenza ha mostrado un marcado incremento en la actividad, superando el umbral elevado. En Colombia, la actividad de SARS-CoV-2 ha presentado un descenso en las cuatro últimas SE situándose en niveles medio-bajos; la actividad de IRAG se ha mantenido en descenso en torno al umbral epidémico durante estas últimas cuatro SE, con los casos positivos atribuibles a influenza y en menor medida SARS-CoV-2 y VRS. En Ecuador, el SARS-CoV-2 ha presentado un incremento en la actividad situándose en niveles medio-altos, la actividad de influenza se ha mantenido por debajo del umbral epidémico y la actividad del VRS se ha mantenido en niveles medios en las cuatro últimas SE. La actividad de IRAG ha fluctuado en torno al umbral moderado, los casos IRAG positivos han sido atribuibles a influenza, SARS-CoV-2 y en menor medida a VRS. En Perú tras un marcado incremento en la actividad del SARS-CoV-2 en semanas previas, se ha mostrado un descenso en las cuatro últimas SE hasta niveles bajos. En Venezuela durante las cuatro últimas SE se ha observado una actividad fluctuante de influenza por debajo del umbral epidémico. Brasil y el Cono Sur: La actividad de IRAG y ETI ha permanecido y en niveles bajos en las últimas cuatro SE, con la mayoría de los casos positivos atribuibles a SARS-CoV-2. La actividad de influenza ha mostrado un incremento en las últimas cuatro SE con niveles en torno al umbral epidémico en algunos países. En este periodo, los virus de influenza predominantes han sido de tipo A(H3N2) y A(H1N1)pdm09 seguidos de B/Victoria. La actividad del VRS se ha mantenido en niveles bajos. La actividad del SARS-CoV-2 se ha mantenido en descenso con niveles elevados. Por países: En Argentina, los niveles de ETI e IRAG han permanecido por debajo del umbral epidémico. El porcentaje de positividad de SARS-CoV-2, aunque permanece con niveles moderados, ha mostrado un marcado descenso en las cuatro últimas SE y la actividad de influenza se encuentra por debajo del umbral epidémico. En Brasil, la actividad del SARS-CoV-2 se ha mantenido en niveles elevados, aunque en descenso, y la actividad de influenza ha mostrado un ascenso durante la cuatro últimas SE superando el umbral epidémico. En Chile, se ha observado un incremento en la actividad del SARS.CoV-2 en las cuatro últimas SE con niveles moderados, y a su vez se ha observado un ascenso en la actividad de influenza que ha superado el umbral epidémico. Los casos de ETI han presentado un ascenso pronunciado con niveles epidémicos; los casos de IRAG han superado ligeramente el umbral epidémico, la mayoría de los casos positivos tanto de ETI como de IRAG son atribuibles a SARS-CoV-2 y en menor medida a influenza. En Paraguay, la circulación del SARS-CoV-2 ha mostrado un descenso en las cuatro últimas SE, encontrándose en niveles bajos y la actividad de influenza y VRS se han mantenido bajas. La actividad de IRAG y ETI se han mantenido por debajo del umbral epidémico. En Uruguay, la actividad de IRAG ha continuado con niveles por debajo del umbral epidémico, aunque con un ligero incremento en las cuatro últimas semanas siendo la mayoría de los escasos casos positivos atribuibles a SARS-CoV-2.

Regional Update, Influenza and Other Respiratory Viruses. Epidemiological Week 8 (1 March 2024)

[WEEKLY SUMMARY]. Regional Situation: Over the past four Epidemiological Weeks (EWs), there has been a decline in lnfluenza-Like lllness (ILI) activity in the Americas region, stabilizing at medium levels. Similarly, a decrease has been observed in the activity of Severe Acute Respiratory lnfection (SARI), currently at low leveis. ln both cases, the observed activity has been associated with positive cases of influenza and SARS-CoV-2. ILI activity has been mainly linked to moderate activity observed in North America, which showed a mild decrease in the past four weeks. Regarding the circulation of respiratory viruses, SARS-CoV-2 activity has remained moderate at the regional level compared to previous epidemie waves. Influenza activity has decreased over the period; respiratory syncytial virus (RSV) activity, while remaining moderate, has also declined. North America: ILI cases have remained at medium-high levels, with most cases attributable to influenza, although showing a decline in this proportion. SARI cases have decreased, with most cases attributable to influenza and, to a lesser extent, SARS-CoV-2. Influenza activity has remained at epidemie levels after a slight decrease in recent EWs. During this period, the predominant influenza viruses have been type A(H 1 N 1)pdm09, with concurrent circulation of influenza A(H3N2) and, to a lesser extent, influenza B/Victoria. RSV activity has declined in the last four EWs, remaining at moderate levels. SARS-CoV-2 positivity has decreased in the last four EWs and remains below late 2023 levels. By countries: ln Canada, SARS-CoV-2 activity has markedly decreased in the last four EWs to medium leveis. Influenza activity remains at epidemie levels, and RSV activity has declined during this period. ln Mexico, influenza circulation has remained fluctuating at epidemie levels in the last four EWs, while an increase in SARS-CoV-2 circulation has been observed. ln the United States, influenza activity has decreased in the past four EWS and remained above the epidemie threshold, RSV activity has decreased to moderate levels, and although SARS-CoV-2 has remained at high levels, it has shown a decreasing trend. Hospitalization rates for influenza, RSV, and SARS-CoV-2, after reaching similar high levels to the previous season, have shown a downward trend in the last four EWs. Caribbean: ILI cases have declined from high levels in preceding weeks to moderate levels in the most recent EW associated with decreases in positive influenza and SARS-Co-V-2 cases; SARI cases have remained on the decline. Influenza activity has increased in the last four EWs, reaching low circulation levels. During the last four EWs, the predominant viruses have been type A(H1 N1)pdm09, followed by A(H3N2) and, to a lesser extent, B/Victoria. RSV activity has remained at low levels. SARS-CoV-2 activity has declined to moderate levels, continuing to show a decreasing trend. By countries: Elevated influenza activity has been observed in Suriname. Central America: ILI and SARI cases have decreased in the last four weeks, with the majority of positive cases attributable to SARSCoV- 2 and, to a lesser extent, influenza. Influenza activity has decreased in the last four EWs, with an increase noted in the most recent EW, however remaining at low levels. During this period, the predominant viruses have been type A(H1 N1)pdm09, followed by A(H3N2) and B/Victoria. RSV activity has decreased to low levels. SARS-CoV-2 activity further declined and remained at low levels. By countries: ln EI Salvador, SARS-CoV-2 activity continued to decline over the past four EWs. ln Guatemala, ILI cases were sustained at high levels and SARI cases while declining to moderate levels showed increasing positivity for SARS-Co-V-2 and influenza. ln Honduras, both ILI and SARI cases increased slightly in the past four EWs, however both remain below epidemie levels. Influenza activity continued at epidemie leveis. ln Nicaragua, RSV activity has continued to decline; both influenza and SARS-CoV-2 levels have remained low. After reaching high levels in early January 2024 in Panama, SARS-CoV-2 activity has decreased. However, after fluctuating around the epidemie threshold in the last four EWs, influenza activity levels have increased to epidemie levels. ILI and SARI cases, have declined in the last four EWs. Andean: ILI activity has remained stable at iow levels, and SARI casesremaineda t high levels, with the highest proportion of positive cases attributable to SARS-CoV-2. Influenza activity has remained at low leveis in the last four EWs. During this period, the predominant influenza viruses have been type A(H1 N1)pdm09, with circulation of A(H3N2) and B/Victoria to a lesser extent. RSV activity has remained at low levels. SARS-CoV-2 activity has declined over the past four EWs. By countries: ln Bolivia, influenza circulation has increased in recent EWs with influenza A(H3N2) dominating. SARI and ILI numbers have, however, remained low. ln Colombia, SARS-CoV-2 activity have declined after an initial increase in mid-January 2024. ln Ecuador, SARS-CoV-2 has shown an increase in activity in the past EW; influenza activity has continued to decline and has remained beneath epidemie thresholds for the past four EWs, and RSV activity has declined. SARI cases have also decreased. ln Peru, SARSCoV- 2 activity has steadily declined over the past four EWs. Influenza activity in Venezuela has increased over the past four EWs with A(H1N1)pdm09 dominating followed by influenza A(H3N2), and influenza B/Victoria. Brazil and the Southem Cone: SARI and ILI activity has remained low in the last four EWs, with most positive cases attributable to SARS-CoV-2. Influenza activity has remained at low circuiation levels during the last four EWs, with a slight increase in the last two EWs. During this period, the predominant influenza viruses have been type A(H3N2) and A(H1N1)pdm09, followed by B/Victoria. RSV activity has remained at low levels. SARS-CoV-2 positivity has remained at high levels, however the number of positives has declined. By countries: ln Argentina, ILI and SARI levels have remained below the epidemie threshold. After an initial inerease in the positivity rate of SARS-CoV-2 in late January, a decline has been observed, remaining at high ievels. ln Brazil, SARS-CoV-2 activity has increased in the past four EWs, remaining at high levels. ln Chile, after a marked deerease, SARS-CoV-2 activity has reeently increased again in the last four EWs, with ILI cases remaining above epidemie levels, however, SARI cases remained just below the epidemie threshold, mostly attributable to SARS-CoV-2. ln Paraguay, SARS-CoV-2 cireulation has shown a decrease in the last three EWs, reaching moderate leveis, and influenza aetivity has increased above the epidemie threshold, while SARI activity has been below epidemie leveis, with most positive cases attributable to SARS-CoV-2. ln Uruguay, SARI activity has continued at levels below the epidemie threshold, with most of the few positive cases attributable to SARS-CoV-2.

[RESUMEN SEMANAL]. Situación regional: Durante las últimas cuatro Semanas Epidemiológicas (SE), ha habido una disminución en la actividad de Enfermedad Tipo Influenza (ETI) en la región de las Américas, estabilizándose en niveles medios. De igual forma, se ha observado una disminución en la actividad de la lnfección Respiratoria Aguda Grave (IRAG), actualmente en niveles bajos. En ambos casos, la actividad observada se ha asociado con casos positivos de influenza y SARS-CoV-2. La actividad de ETI se ha relacionado principalmente con la actividad moderada observada en América dei Norte, que mostrá una leve disminución en las últimas cuatro semanas. En cuanto a la circulación de virus respiratorios, la actividad dei SARS-CoV-2 se ha mantenido moderada a nivel regional en comparación con oleadas epidémicas anteriores. La actividad de la influenza ha disminuido durante el período; La actividad dei virus respiratorio sincicial (VRS), aunque sigue siendo moderada, también ha disminuido. América dei Norte: los casos de ETI se han mantenido en niveles medio-altos, y la mayoría de los casos son atribuibles a la influenza, aunque muestran una disminución en esta proporción. Los casos de IRAG han disminuido, y la mayoría de los casos son atribuibles a la influenza y, en menor medida, ai SARS-CoV-2. La actividad de la influenza se ha mantenido en niveles epidémicos después de una ligera disminudón en las SE redentes. Durante este período, los virus de influenza predominantes han sido el tipo A(H1 N1)pdm09, con circulación concurrente de influenza A(H3N2) y, en menor medida, influenza BNictoria. La actividad dei VRS ha disminuido en las últimas cuatro SE, manteniéndose en niveles moderados. La positividad dei SARS-CoV-2 ha disminuido en las últimas cuatro SE y se mantiene por debajo de los niveles de finales de 2023. Por países: En Canadá, la actividad dei SARS-CoV-2 ha disminuido notablemente en las últimas cuatro SE hasta niveles medias. La actividad de la influenza se mantiene en niveles epidémicos y la actividad dei VRS ha disminuido durante este período. En México, la circulación de influenza se ha mantenido fluctuando a niveles epidémicos en las últimas cuatro SE, mientras que se observa un aumento en la circuladón de SARS-CoV-2. En los Estados Unidos, la actividad de la influenza disminuyó en los últimos cuatro SE y se mantuvo por encima dei umbral epidémico, la actividad dei VRS disminuyó a niveles moderados y, aunque el SARS-CoV-2 se mantuvo en niveles altos, mostrá una tendenda decreciente. Las tasas de hospitalización por influenza, VRS y SARS-CoV-2, luego de alcanzar niveles similares a los de la temporada anterior, han mostrado una tendencia a la baja en las últimas cuatro SE. Caribe: Los casos de ETI han disminuido desde niveles altos en las semanas anteriores a niveles moderados en la SE más redente asodado con disminuciones en los casos positivos de influenza y SARS-Co-V-2; Los casos de IRAG han seguido disminuyendo. La actividad de influenza ha aumentado en las últimas cuatro SE, alcanzando niveles bajos de drculación. Durante las últimas cuatro SE, los virus predominantes han sido el tipo A(H1N1)pdm09, seguido dei A(H3N2) y, en menor medida, el BNictoria. La actividad dei VRS se ha mantenido en niveles bajos. La actividad dei SARS-CoV-2 ha disminuido a niveles moderados y continúa mostrando una tendencia decreciente. Por países: Se ha observado una elevada actividad de influenza en Surinam. Centroamérica: Los casos de ETI e IRAG han disminuido en las últimas cuatro semanas, siendo la mayoría de los casos positivos atribuibles ai SARS-CoV-2 y, en menor medida, a la influenza. La actividad de influenza ha disminuido en las últimas cuatro SE, observándose un aumento en la SE más redente, aunque se mantiene en niveles bajos. Durante este período los virus predominantes han sido el tipo A(H1N1)pdm09, seguido dei A(H3N2) y BNictoria. La actividad dei VRS ha disminuido a niveles bajos. La actividad dei SARS-CoV-2 siguió disminuyendo y se mantuvo en niveles bajos. Por países: En EI Salvador, la actividad dei SARS-CoV-2 continuá disminuyendo durante las últimas cuatro SE. En Guatemala, los casos de ETI se mantuvieron en niveles altos y los casos de IRAG, aunque disminuyeron a niveles moderados, mostraron una positividad creciente para el SARS-Co-V-2 y la influenza. En Honduras, tanto los casos de ETI como de IRAG aumentaron ligeramente en las últimas cuatro SE, sin embargo, ambos permanecen por debajo de los niveles epidémicos. La actividad gripal continuá a niveles epidémicos. En Nicaragua, la actividad dei VRS ha seguido disminuyendo; Tanto los niveles de influenza como de SARS-CoV- 2 se han mantenido bajos. Después de alcanzar niveles elevados a principies de enero de 2024 en Panamá, la actividad dei SARSCoV- 2 ha disminuido. Sin embargo, después de fluctuar alrededor dei umbral epidémico en las últimas cuatro SE, los niveles de actividad de la influenza han aumentado a niveles epidémicos. Los casos de ETI e IRAG han disminuido en las últimas cuatro SE. Andino: La actividad de ETI se ha mantenido estable en niveles bajos y los casos de IRAG se mantuvieron en niveles altos, siendo la mayor proporción de casos positivos atribuibles ai SARS-CoV-2. La actividad de influenza se ha mantenido en niveles bajos en las últimas cuatro SE. Durante este período, los virus de influenza predominantes han sido el tipo A(H1 N1)pdm09, con circulación de A(H3N2) y BNictoria en menor medida. La actividad dei VRS se ha mantenido en niveles bajos. La actividad dei SARS-CoV-2 ha disminuido en las últimas cuatro SE. Por países: En Bolivia la circulación de influenza ha aumentado en las últimas SE, predominando la influenza A(H3N2). Sin embargo, las cifras de IRAG y ETI se han mantenido bajas. En Colombia, la actividad dei SARS-CoV-2 ha disminuido luego de un aumento inicial a mediados de enero de 2024. En Ecuador, el SARS-CoV-2 ha mostrado un aumento en la actividad en la pasada SE; la actividad de la influenza ha seguido disminuyendo y se ha mantenido por debajo de los umbrales epidémicos durante las últimas cuatro SE, y la actividad dei VRS ha disminuido. Los casos de IRAG también han disminuido. En Perú, la actividad dei SARS-CoV-2 ha disminuido constantemente durante las últimas cuatro SE. La actividad de influenza en Venezuela ha aumentado en las últimas cuatro SE, con A(H1N1)pdm09 dominando seguido de influenza A(H3N2) e influenza BNictoria. Brasil y Cono Sur: La actividad de IRAG y ETI se ha mantenido baja en las últimas cuatro SE, siendo la mayoría de los casos positivos atribuibles ai SARS-CoV-2. La actividad de influenza se ha mantenido en niveles de circulación bajos durante las últimas cuatro SE, con un ligero aumento en las últimas dos SE. Durante este período, los vírus de influenza predominantes han sido el tipo A(H3N2) y A(H1N1)pdm09, seguidos por el BNictoria. La actividad dei VRS se ha mantenido en niveles bajos. La positividad dei SARS-CoV-2 se ha mantenido en niveles elevados, sin embargo, el número de positivos ha disminuido. Por países: En Argentina los niveles de ETI e IRAG se han mantenido por debajo dei umbral epidémico. Tras un aumento inicial de la tasa de positividad dei SARS-CoV-2 a finales de enero, se ha observado un descenso, manteniéndose en niveles elevados. En Brasil, la actividad dei SARS-CoV-2 ha aumentado en las últimas cuatro SE y se mantiene en niveles elevados. En Chile, después de una marcada disminución, la actividad dei SARS-CoV-2 recientemente aumentá nuevamente en las últimas cuatro SE, y los casos de ETI se mantuvieron por encima de los niveles epidémicos; sin embargo, los casos de IRAG se mantuvieronjusto por debajo dei umbral epidémico, en su mayoría atribuibles ai SARS-CoV-2. En Paraguay, la circulación de SARS-CoV-2 ha mostrado una disminución en las últimas tres SE, alcanzando niveles moderados, y la actividad de influenza ha aumentado por encima dei umbral epidémico, mientras que la actividad de IRAG ha estado por debajo de los niveles epidémicos, siendo la mayoría de los casos positivos atribuibles ai SARS-CoV-2. En Uruguay, la actividad de IRAG ha continuado en niveles por debajo dei umbral epidémico, y la mayoría de los pocos casos positivos son atribuibles ai SARS-CoV-2.

Regional Update, Influenza and Other Respiratory Viruses. Epidemiological Week 9 (8 March 2024)

[WEEKLY SUMMARY]. Regional Situation: Over the past tour Epidemiological Weeks (EWs), there has been a decline in lnfluenza-Like lllness (ILI) activity in the Americas region, stabilizing at medium levels. Similarly, a decrease has been observed in the activity of Severe Acute Respiratory lnfection (SARI), currently at low levels. In both cases, the observed activity has been associated with positive cases of influenza and SARS-CoV-2. ILI activity has been mainly linked to moderate activity observed in North America, which showed a mild decrease in the past tour weeks. Regarding the circulation of respiratory viruses, SARS-CoV-2 activity has remained moderate at the regional level compared to previous epidemic waves. Influenza activity has decreased over the period; respiratory syncytial virus (RSV) activity, while remaining moderate, has also declined. North America: ILI cases have remained at medium-high levels, with most cases attributable to influenza, although showing a decline in this proportion. SARI cases have decreased, with most cases attributable to influenza and, to a lesser extent, SARS-CoV-2. Influenza activity has remained at epidemic levels after a slight decrease in recent EWs. During this period, the predominant influenza viruses have been type A(H 1 N 1 )pdm09, with concurrent circulation of influenza A(H3N2) and, to a lesser extent, influenza B/Victoria. RSV activity has declined in the last tour EWs, remaining at moderate levels. SARS-CoV-2 positivity has decreased in the last tour EWs and remains below late 2023 levels. By countries: In Canada, SARS-CoV-2 activity has markedly decreased in the last tour EWs to medium levels. Influenza activity remains at epidemic levels, and RSV activity has declined during this period. In Mexico, influenza circulation has remained fluctuating at epidemic levels in the last tour EWs, while an increase in SARS-CoV-2 circulation has been observed. In the United States, influenza activity has decreased in the past tour EWS and remained above the epidemic threshold, RSV activity has decreased to moderate levels, and although SARS-CoV-2 has remained at high levels, it has shown a decreasing trend. Hospitalization rates tor influenza, RSV, and SARS-CoV-2, after reaching similar high levels to the previous season, have shown a downward trend in the last tour EWs. Caribbean: ILI cases have declined from high levels in preceding weeks to moderate levels in the most recent EW associated with decreases in positive influenza and SARS-Co-V-2 cases; SARI cases have remained on the decline. Influenza activity has increased in the last tour EWs, reaching low circulation levels. During the last tour EWs, the predominant viruses have been type A(H1 N1)pdm09, tollowed by A(H3N2) and, to a lesser extent, B/Victoria. RSV activity has remained at low levels. SARS-CoV-2 activity has declined to moderate levels, continuing to show a decreasing trend. By countries: Elevated influenza activity has been observed in Suriname. Central America: ILI and SARI cases have decreased in the last tour weeks, with the majority of positive cases attributable to SARSCoV- 2 and, to a lesser extent, influenza. Influenza activity has decreased in the last tour EWs, with an increase noted in the most recent EW, however remaining at low levels. During this period, the predominant viruses have been type A(H 1 N 1 )pdm09, tollowed by A(H3N2) and B/Victoria. RSV activity has decreased to low levels. SARS-CoV-2 activity further declined and remained at low levels. By countries: In El Salvador, SARS-CoV-2 activity continued to decline over the past tour EWs. In Guatemala, ILI cases were sustained at high levels and SARI cases while declining to moderate levels showed increasing positivity tor SARS-Co-V-2 and influenza. In Honduras, both ILI and SARI cases increased slightly in the past tour EWs, however both remain below epidemic levels. Influenza activity continued at epidemic levels. In Nicaragua, RSV activity has continued to decline; both influenza and SARS-CoV-2 levels have remained low. After reaching high levels in early January 2024 in Panama, SARS-CoV-2 activity has decreased. However, after fluctuating around the epidemic threshold in the last tour EWs, influenza activity levels have increased to epidemic levels. ILI and SARI cases, have declined in the last tour EWs. Andean: ILI activity has remained stable at low levels, and SARI casesremaineda t high levels, with the highest proportion of positive cases attributable to SARS-CoV-2. Influenza activity has remained at low levels in the last four EWs. During this period, the predominant influenza viruses have been type A(H 1 N 1 )pdm09, with circulation of A(H3N2) and B/Victoria to a lesser extent. RSV activity has remained at low levels. SARS-CoV-2 activity has declined over the past four EWs. By countries: In Bolivia, influenza circulation has increased in recent EWs with influenza A(H3N2) dominating. SARI and ILI numbers have, however, remained low. In Colombia, SARS-CoV-2 activity have declined after an initial increase in mid-January 2024. In Ecuador, SARS-CoV-2 has shown an increase in activity in the past EW; influenza activity has continued to decline and has remained beneath epidemic thresholds far the past four EWs, and RSV activity has declined. SARI cases have also decreased. In Peru, SARSCoV- 2 activity has steadily declined over the past four EWs. Influenza activity in Venezuela has increased over the past four EWs with A(H1 N1)pdm09 dominating followed by influenza A(H3N2), and influenza B/Victoria. Brazil and the Southern Cone: SARI and ILI activity has remained low in the last four EWs, with most positive cases attributable to SARS-CoV-2. Influenza activity has remained at low circulation levels during the last four EWs, with a slight increase in the last two EWs. During this period, the predominant influenza viruses have been type A(H3N2) and A(H1 N1)pdm09, followed by B/Victoria. RSV activity has remained at low levels. SARS-CoV-2 positivity has remained at high levels, however the number of positives has declined. By countries: In Argentina, ILI and SARI levels have remained below the epidemic threshold. After an initial increase in the positivity rate of SARS-CoV-2 in late January, a decline has been observed, remaining at high levels. In Brazil, SARS-CoV-2 activity has increased in the past four EWs, remaining at high levels. In Chile, after a marked decrease, SARS-CoV-2 activity has recently increased again in the last four EWs, with ILI cases remaining above epidemic levels, however, SARI cases remained just below the epidemic threshold, mostly attributable to SARS-CoV-2. In Paraguay, SARS-CoV-2 circulation has shown a decrease in the last three EWs, reaching moderate levels, and influenza activity has increased above the epidemic threshold, while SARI activity has been below epidemic levels, with most positive cases attributable to SARS-CoV-2. In Uruguay, SARI activity has continued at levels below the epidemic threshold, with most of the few positive cases attributable to SARS-CoV-2.

[RESUMEN SEMANAL]. Situación regional: Durante las últimas cuatro Semanas Epidemiológicas (SE), ha habido una disminución en la actividad de Enfermedad Tipo Influenza (ETI) en la región de las Américas, estabilizándose en niveles medios. De igual forma, se ha observado una disminución en la actividad de la Infección Respiratoria Aguda Grave (IRAG), actualmente en niveles bajos. En ambos casos, la actividad observada se ha asociado con casos positivos de influenza y SARS-CoV-2. La actividad de ETI se ha relacionado principalmente con la actividad moderada observada en América del Norte, que mostró una leve disminución en las últimas cuatro semanas. En cuanto a la circulación de virus respiratorios, la actividad del SARS-CoV-2 se ha mantenido moderada a nivel regional en comparación con oleadas epidémicas anteriores. La actividad de la influenza ha disminuido durante el período; La actividad del virus respiratorio sincicial (VRS), aunque sigue siendo moderada, también ha disminuido. América del Norte: los casos de ETI se han mantenido en niveles medio-altos, y la mayoría de los casos son atribuibles a la influenza, aunque muestran una disminución en esta proporción. Los casos de IRAG han disminuido, y la mayoría de los casos son atribuibles a la influenza y, en menor medida, al SARS-CoV-2. La actividad de la influenza se ha mantenido en niveles epidémicos después de una ligera disminución en las SE recientes. Durante este período, los virus de influenza predominantes han sido el tipo A(H1 N1)pdm09, con circulación concurrente de influenza A(H3N2) y, en menor medida, influenza B/Victoria. La actividad del VRS ha disminuido en las últimas cuatro SE, manteniéndose en niveles moderados. La positividad del SARS-CoV-2 ha disminuido en las últimas cuatro SE y se mantiene por debajo de los niveles de finales de 2023. Por países: En Canadá, la actividad del SARS-CoV-2 ha disminuido notablemente en las últimas cuatro SE hasta niveles medios. La actividad de la influenza se mantiene en niveles epidémicos y la actividad del VRS ha disminuido durante este período. En México, la circulación de influenza se ha mantenido fluctuando a niveles epidémicos en las últimas cuatro SE, mientras que se observa un aumento en la circulación de SARS-CoV-2. En los Estados Unidos, la actividad de la influenza disminuyó en los últimos cuatro SE y se mantuvo por encima del umbral epidémico, la actividad del VRS disminuyó a niveles moderados y, aunque el SARS-CoV-2 se mantuvo en niveles altos, mostró una tendencia decreciente. Las tasas de hospitalización por influenza, VRS y SARS-CoV-2, luego de alcanzar niveles similares a los de la temporada anterior, han mostrado una tendencia a la baja en las últimas cuatro SE. Caribe: Los casos de ETI han disminuido desde niveles altos en las semanas anteriores a niveles moderados en la SE más reciente asociado con disminuciones en los casos positivos de influenza y SARS-Co-V-2; Los casos de IRAG han seguido disminuyendo. La actividad de influenza ha aumentado en las últimas cuatro SE, alcanzando niveles bajos de circulación. Durante las últimas cuatro SE, los virus predominantes han sido el tipo A(H1 N1)pdm09, seguido del A(H3N2) y, en menor medida, el B/Victoria. La actividad del VRS se ha mantenido en niveles bajos. La actividad del SARS-CoV-2 ha disminuido a niveles moderados y continúa mostrando una tendencia decreciente. Por países: Se ha observado una elevada actividad de influenza en Surinam. Centroamérica: Los casos de ETI e IRAG han disminuido en las últimas cuatro semanas, siendo la mayoría de los casos positivos atribuibles al SARS-CoV-2 y, en menor medida, a la influenza. La actividad de influenza ha disminuido en las últimas cuatro SE, observándose un aumento en la SE más reciente, aunque se mantiene en niveles bajos. Durante este periodo los virus predominantes han sido el tipo A(H 1 N 1 )pdm09, seguido del A(H3N2) y B/Victoria. La actividad del VRS ha disminuido a niveles bajos. La actividad del SARS-CoV-2 siguió disminuyendo y se mantuvo en niveles bajos. Por países: En El Salvador, la actividad del SARS-CoV-2 continuó disminuyendo durante las últimas cuatro SE. En Guatemala, los casos de ETI se mantuvieron en niveles altos y los casos de IRAG, aunque disminuyeron a niveles moderados, mostraron una positividad creciente para el SARS-Co-V-2 y la influenza. En Honduras, tanto los casos de ETI como de IRAG aumentaron ligeramente en las últimas cuatro SE, sin embargo, ambos permanecen por debajo de los niveles epidémicos. La actividad gripal continuó a niveles epidémicos. En Nicaragua, la actividad del VRS ha seguido disminuyendo; Tanto los niveles de influenza como de SARS-CoV- 2 se han mantenido bajos. Después de alcanzar niveles elevados a principios de enero de 2024 en Panamá, la actividad del SARSCoV- 2 ha disminuido. Sin embargo, después de fluctuar alrededor del umbral epidémico en las últimas cuatro SE, los niveles de actividad de la influenza han aumentado a niveles epidémicos. Los casos de ETI e IRAG han disminuido en las últimas cuatro SE. Andino: La actividad de ETI se ha mantenido estable en niveles bajos y los casos de IRAG se mantuvieron en niveles altos, siendo la mayor proporción de casos positivos atribuibles al SARS-CoV-2. La actividad de influenza se ha mantenido en niveles bajos en las últimas cuatro SE. Durante este período, los virus de influenza predominantes han sido el tipo A(H1 N1)pdm09, con circulación de A(H3N2) y B/Victoria en menor medida. La actividad del VRS se ha mantenido en niveles bajos. La actividad del SARS-CoV-2 ha disminuido en las últimas cuatro SE. Por países: En Bolivia la circulación de influenza ha aumentado en las últimas SE, predominando la influenza A(H3N2). Sin embargo, las cifras de IRAG y ETI se han mantenido bajas. En Colombia, la actividad del SARS-CoV-2 ha disminuido luego de un aumento inicial a mediados de enero de 2024. En Ecuador, el SARS-CoV-2 ha mostrado un aumento en la actividad en la pasada SE; la actividad de la influenza ha seguido disminuyendo y se ha mantenido por debajo de los umbrales epidémicos durante las últimas cuatro SE, y la actividad del VRS ha disminuido. Los casos de IRAG también han disminuido. En Perú, la actividad del SARS-CoV-2 ha disminuido constantemente durante las últimas cuatro SE. La actividad de influenza en Venezuela ha aumentado en las últimas cuatro SE, con A(H1N1)pdm09 dominando seguido de influenza A(H3N2) e influenza B/Victoria. Brasil y Cono Sur: La actividad de IRAG y ETI se ha mantenido baja en las últimas cuatro SE, siendo la mayoría de los casos positivos atribuibles al SARS-CoV-2. La actividad de influenza se ha mantenido en niveles de circulación bajos durante las últimas cuatro SE, con un ligero aumento en las últimas dos SE. Durante este período, los virus de influenza predominantes han sido el tipo A(H3N2) y A(H1 N1)pdm09, seguidos por el B/Victoria. La actividad del VRS se ha mantenido en niveles bajos. La positividad del SARS-CoV-2 se ha mantenido en niveles elevados, sin embargo, el número de positivos ha disminuido. Por países: En Argentina los niveles de ETI e IRAG se han mantenido por debajo del umbral epidémico. Tras un aumento inicial de la tasa de positividad del SARS-CoV-2 a finales de enero, se ha observado un descenso, manteniéndose en niveles elevados. En Brasil, la actividad del SARS-CoV-2 ha aumentado en las últimas cuatro SE y se mantiene en niveles elevados. En Chile, después de una marcada disminución, la actividad del SARS-CoV-2 recientemente aumentó nuevamente en las últimas cuatro SE, y los casos de ETI se mantuvieron por encima de los niveles epidémicos; sin embargo, los casos de IRAG se mantuvieron justo por debajo del umbral epidémico, en su mayoría atribuibles al SARS-CoV-2. En Paraguay, la circulación de SARS-CoV-2 ha mostrado una disminución en las últimas tres SE, alcanzando niveles moderados, y la actividad de influenza ha aumentado por encima del umbral epidémico, mientras que la actividad de IRAG ha estado por debajo de los niveles epidémicos, siendo la mayoría de los casos positivos atribuibles al SARS-CoV-2. En Uruguay, la actividad de IRAG ha continuado en niveles por debajo del umbral epidémico, y la mayoría de los pocos casos positivos son atribuibles al SARS-CoV-2.