Rocky Mountain Spotted Fever Mimicking Multisystem Inflammatory Syndrome in Hospitalized Children, Sonora, Mexico.

We describe 5 children who had Rocky Mountain spotted fever (RMSF) and manifested clinical symptoms similar to multisystem inflammatory syndrome in Sonora, Mexico, where RMSF is hyperendemic. Physicians should consider RMSF in differential diagnoses of hospitalized patients with multisystem inflammatory syndrome to prevent illness and death caused by rickettsial disease.

Impact of COVID-19 vaccination on clinical outcomes in kidney transplant patients.

INTRODUCTION: The global health crisis caused by the COVID-19 pandemic has resulted in severe mortality and morbidity. Immunosuppressed patients, such as kidney transplant recipients, are particularly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. OBJECTIVE: The aim of this cohort study was to evaluate the impact of COVID-19 vaccination on clinical outcomes in patients with kidney transplants. MATERIALS AND METHODS: In this retrospective study, 254 patients with kidney transplants were vaccinated against SARS-CoV-2 and a fraction of these contracted COVID-19. The diagnosis of COVID-19 was carried out by reverse transcriptase-polymerase chain reaction testing, and the patients received treatment involving immunosuppressive and COVID-19-specific protocols. RESULTS: SARS-CoV-2 infection was diagnosed in 38 (14.96%) patients before the COVID-19 vaccine was administered. After vaccination, an additional 29 (11.42%) patients were diagnosed with COVID-19. Risk factors for hospitalization included age, body mass index (BMI), comorbidities, and time elapsed since renal transplantation (p = 0.025, 0.038, 0.012, and 0.046, respectively). COVID-19 vaccination resulted in a significant decrease in the rate of hospital-acquired SARS-CoV-2 infection from 63.16% to 34.48% (p = 0.020). The proportion of patients from this cohort placed in intensive care units decreased from 23.68% to zero. Allograft rejections exhibited a decreasing trend from 13.16% to 6.90% (p = 0.690). This patient cohort displayed 15.79% mortality prior to COVID-19 vaccination that was reduced to nil after immunization. CONCLUSION: COVID-19 vaccination significantly reduced COVID-19 severity and mortality in this cohort of patients with kidney transplants. The risk factors for hospitalization were determined to be age, BMI, comorbidities, and time since renal transplantation. COVID-19 vaccination resulted in a clinical outcome of reduced hospitalization and a decrease in clinical complications. The COVID-19 vaccination-derived adverse effects in this cohort were found to be comparable to those in the immunocompetent population.

Drugs and natural products for the treatment of COVID-19 during 2020, the first year of the pandemic.

This work aimed to show which treatments showed efficacy against coronavirus disease 2019 (COVID-19); therefore, the results of 37 clinical trials started in 2020 and completed in 2021 are reviewed and discussed here. These were selected from databases, excluding vaccines, computational studies, in silico, in vitro, and those with hyperimmune sera from recovered patients. We found 34 drugs, one vitamin, and one herbal remedy with pharmacological activity against symptomatic COVID-19. They reduced mortality, disease progression, or recovery time. For each treatment, the identifier and type of trial, the severity of the disease, the sponsor, the country where the trial was conducted, and the trial results are presented. The drugs were classified according to their mechanism of action. Several drugs that reduced mortality also reduced inflammation in the most severe cases. These include some that are not considered anti-inflammatory, such as Aviptadil, pyridostigmine bromide, anakinra, imatinib, baricitinib, and bevacizumab, as well as the combination of ivermectin, aspirin, dexamethasone, and enoxaparin. Nigella sativa seeds with honey have also been reported to have therapeutic activity. On the other hand, tofacitinib, novaferon with ritonavir, and lopinavir were also effective, as well as in combination with antiviral therapies such as danoprevir with ritonavir. The natural products colchicine and Vitamin D3 were only effective in patients with mild-to-moderate COVID-19, as was hydroxychloroquine. Drug repositioning has been the main tool in the search for effective therapies by expanding the pharmacological options available to patients.

El objetivo del presente trabajo fue conocer qué tratamientos mostraron efectividad contra COVID-19, para lo cual se revisan y discuten los resultados de 37 estudios clínicos iniciados durante 2020 y concluidos en 2021. Estos fueron seleccionados de bases de datos, excluyendo vacunas, estudios computacionales, in silico, in vitro y con sueros hiperinmunes de pacientes recuperados. Se documentaron 34 fármacos, una vitamina y un remedio herbolario, con actividad farmacológica ante COVID-19 sintomático. Estos redujeron la mortalidad, el progreso de la enfermedad, o el tiempo de recuperación. Para cada tratamiento se presenta identificador y tipo de estudio, la gravedad de la enfermedad, patrocinador, país donde se realizó, así como sus resultados. Los fármacos se clasificaron de acuerdo con su mecanismo de acción. Varios fármacos que redujeron la mortalidad también disminuyeron la inflamación en los casos más graves. Esto incluyendo algunos no considerados antiinflamatorios, como el aviptadil, el bromuro de piridostigmina, el anakinra, el imatinib, el baricitinib y el bevacizumab, así como la combinación de ivermectina, aspirina, dexametasona y enoxaparina. También se reportaron con actividad terapéutica las semillas de Nigella sativa con miel. Además, resultaron efectivos el tofacitinib, el novaferón con ritonavir y lopinavir, así como los antivirales en terapias combinadas como el danoprevir con ritonavir. Los productos naturales colchicina y vitamina D3, solo tuvieron actividad en los pacientes en estado leve a moderado de la COVID-19, así como la hidroxicloroquina. El reposicionamiento de fármacos fue la principal herramienta para buscar terapias efectivas ampliando las opciones farmacológicas accesibles a los pacientes.

Drugs and natural products for the treatment of COVID-19 during 2020, the first year of the pandemic / Fármacos y productos naturales para el tratamiento de la COVID-19 durante 2020, el primer año de la pandemia

Abstract This work aimed to show which treatments showed efficacy against coronavirus disease 2019 (COVID-19); therefore, the results of 37 clinical trials started in 2020 and completed in 2021 are reviewed and discussed here. These were selected from databases, excluding vaccines, computational studies, in silico, in vitro, and those with hyperimmune sera from recovered patients. We found 34 drugs, one vitamin, and one herbal remedy with pharmacological activity against symptomatic COVID-19. They reduced mortality, disease progression, or recovery time. For each treatment, the identifier and type of trial, the severity of the disease, the sponsor, the country where the trial was conducted, and the trial results are presented. The drugs were classified according to their mechanism of action. Several drugs that reduced mortality also reduced inflammation in the most severe cases. These include some that are not considered anti-inflammatory, such as Aviptadil, pyridostigmine bromide, anakinra, imatinib, baricitinib, and bevacizumab, as well as the combination of ivermectin, aspirin, dexamethasone, and enoxaparin. Nigella sativa seeds with honey have also been reported to have therapeutic activity. On the other hand, tofacitinib, novaferon with ritonavir, and lopinavir were also effective, as well as in combination with antiviral therapies such as danoprevir with ritonavir. The natural products colchicine and Vitamin D3 were only effective in patients with mild-to-moderate COVID-19, as was hydroxychloroquine. Drug repositioning has been the main tool in the search for effective therapies by expanding the pharmacological options available to patients.

Resumen El objetivo del presente trabajo fue conocer qué tratamientos mostraron efectividad contra COVID-19, para lo cual se revisan y discuten los resultados de 37 estudios clínicos iniciados durante 2020 y concluidos en 2021. Estos fueron seleccionados de bases de datos, excluyendo vacunas, estudios computacionales, in silico, in vitro y con sueros hiperinmunes de pacientes recuperados. Se documentaron 34 fármacos, una vitamina y un remedio herbolario, con actividad farmacológica ante COVID-19 sintomático. Estos redujeron la mortalidad, el progreso de la enfermedad, o el tiempo de recuperación. Para cada tratamiento se presenta identificador y tipo de estudio, la gravedad de la enfermedad, patrocinador, país donde se realizó, así como sus resultados. Los fármacos se clasificaron de acuerdo con su mecanismo de acción. Varios fármacos que redujeron la mortalidad también disminuyeron la inflamación en los casos más graves. Esto incluyendo algunos no considerados antiinflamatorios, como el aviptadil, el bromuro de piridostigmina, el anakinra, el imatinib, el baricitinib y el bevacizumab, así como la combinación de ivermectina, aspirina, dexametasona y enoxaparina. También se reportaron con actividad terapéutica las semillas de Nigella sativa con miel. Además, resultaron efectivos el tofacitinib, el novaferón con ritonavir y lopinavir, así como los antivirales en terapias combinadas como el danoprevir con ritonavir. Los productos naturales colchicina y vitamina D3, solo tuvieron actividad en los pacientes en estado leve a moderado de la COVID-19, así como la hidroxicloroquina. El reposicionamiento de fármacos fue la principal herramienta para buscar terapias efectivas ampliando las opciones farmacológicas accesibles a los pacientes.

Natural and Synthetic Coumarins as Potential Drug Candidates Against SARS-CoV-2/CoViD-19.

COVID-19, an airborne disease caused by a betacoronavirus named SARS-- CoV-2, was officially declared a pandemic in early 2020, resulting in more than 770 million confirmed cases and over 6.9 million deaths by September 2023. Although the introduction of vaccines in late 2020 helped reduce the number of deaths, the global effort to fight COVID-19 is far from over. While significant progress has been made in a short period, the fight against SARS-CoV-2/COVID-19 and other potential pandemic threats continues. Like AIDS and hepatitis C epidemics, controlling the spread of COVID-19 will require the development of multiple drugs to weaken the virus's resistance to different drug treatments. Therefore, it is essential to continue developing new drug candidates derived from natural or synthetic small molecules. Coumarins are a promising drug design and development scaffold due to their synthetic versatility and unique physicochemical properties. Numerous examples reported in scientific literature, mainly by in silico prospection, demonstrate their potential contribution to the rapid development of drugs against SARS-CoV-2/COVID-19 and other emergent and reemergent viruses.

Betacoronavirus Infection Outbreak, São Paulo, Brazil, Fall 2023.

We report a human coronavirus OC43 infection outbreak in hospitalized patients and healthcare workers in São Paulo, Brazil, occurring after SARS-CoV-2 cases disappeared. Infection was associated with healthcare workers in 5 (29.4%) patients. Routine surveillance including a respiratory virus panel can improve coronavirus detection in both healthcare professionals and patients.

Substantial Diversity in Cocirculating Omicron Lineages in Hospital Setting, Porto Alegre, Brazil.

We describe substantial variant diversity among 23 detected SARS-CoV-2 Omicron lineage viruses cocirculating among healthcare workers and inpatients (272 sequenced samples) from Porto Alegre, Brazil, during November 2022-January 2023. BQ.1 and related lineages (61.4%) were most common, followed by BE.9 (19.1%), first described in November 2022 in the Amazon region.

Postoperative complications and predictors of mortality in patients with COVID-19.

BACKGROUND: There are limited data about the perioperative outcomes of coronavirus disease 2019 (COVID-19) patients that needed emergency general surgery. The aim of the present study was to describe the perioperative outcomes and mortality of patients with COVID-19 who underwent emergency surgery. MATERIALS AND METHODs: Retrospective study of COVID-19 patients symptomatic versus asymptomatic from March 2020 to February 2022 that needed an emergency surgery in a national referral hospital. RESULTS: Forty-four patients were included in this study. Patients with symptomatic COVID-19 have higher ICU admissions and prolonged length of stay (LOS) as compared with asymptomatic COVID-19 patients. The 90-day survival probability of the entire cohort was 70.1% (60.3-79.9) and was significantly lower in patients with COVID-19 symptomatic 63.4% (50.5-76.2). The cut-off preoperative values for the prediction of mortality: Ferritin ≥ 438.5 ng/mL (Area under the curve [AUC] = 0.908), C-reactive protein (CRP) ≥ 12.5 mg/dL (AUC = 0.715), leukocyte ≥ 13.8 × 103/mL (AUC = 0.706), and albumin ≤ 2.78 g/dL (AUC = 704). Furthermore, a cut-off value of CRP of ≥ 12.5 mg/dL yielded an accuracy of 82.9% for the prediction of postoperative complications (p < 0.001). CONCLUSION: Patients with symptomatic COVID-19 who needed emergency surgery have higher ICU admissions, prolonged LOS, and decreased 90-day survival as compared with asymptomatic COVID-19 patients. Preoperative ferritin, CRP, leukocytes, and albumin could be used as predictors of mortality.

ANTECEDENTES: Hay datos limitados sobre los pacientes con COVID-19 que necesitaron cirugía de emergencia. El objetivo del presente estudio fue describir los resultados perioperatorios y la mortalidad de pacientes con COVID-19 que se sometieron a cirugía de emergencia. MATERIAL Y MÉTODOS: Estudio retrospectivo de pacientes con COVID-19 sintomáticos vs. asintomáticos de marzo 2020 a febrero 2022 que requirieron cirugía de emergencia en un Hospital de Referencia Nacional. RESULTADOS: Se incluyeron 44 pacientes. Los pacientes con COVID-19 sintomático tienen más admisiones en la UCI y estancia hospitalaria prolongada en comparación con los pacientes con COVID-19 asintomático. La supervivencia a 90 días de la cohorte fue del 70,1% (60,3-79,9) y fue menor en los pacientes con COVID-19 sintomáticos del 63.4% (50.5-76.2). Los valores preoperatorios para la predicción de mortalidad: ferritina ≥ 438.5 ng/mL (AUC = 0.908), PCR ≥ 12.5 mg/dL (AUC = 0.715), leucocitos ≥ 13.8 × 103/mL (AUC = 0.706) y albúmina ≤ 2.78 g/dl (AUC = 704). La PCR de ≥ 12.5 mg/dL tiene una precisión del 82.9% para la predicción de complicaciones posoperatorias (p < 0.001). CONCLUSIÓN: Los pacientes con COVID-19 sintomático tienen más admisiones en la UCI, estancia hospitalaria prolongada y menor supervivencia en comparación con los pacientes con COVID-19 asintomáticos. La ferritina, PCR, leucocitos y albúmina preoperatoria pueden utilizarse como predictores de mortalidad.

Reverse transcription loop­mediated isothermal amplification has a high performance in the detection of SARS­CoV­2 in saliva samples and nasal swabs from asymptomatic and symptomatic individuals.

The detection of coronavirus disease 2019 cases represents a significant challenge at the epidemiological level. Limitations exist in effectively detecting asymptomatic cases, achieving good follow-up in hospitals without the infrastructure for reverse transcription-quantitative PCR (RT-qPCR) or in difficult-to-access areas and developing methods with the need for less invasive sampling procedures. Therefore, the present study evaluated the performance of the direct reverse transcription loop-mediated isothermal amplification (RT-LAMP) test for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the saliva and nasal samples of asymptomatic individuals belonging to the university population. In addition, this test was also assessed for effectiveness in symptomatic individuals referred from a hospital with poor infrastructure in molecular biology and located outside the urban area. The RT-LAMP assay was compared with the results obtained from the RT-qPCR nasopharyngeal swab test, where the diagnosis was confirmed by lateral flow immunoassay test for rapid antigen detection. A total of 128 samples were analyzed, of which 43% were symptomatic positive individuals, 25% were asymptomatic positive individuals and 32% were SARS-CoV2-negative control individuals. Among positive individuals, no differences were found between the Cq values determined by RT-qPCR. A sensitivity of 96.5% and a specificity of 97.6% was reported for the detection of SARS-CoV-2 in symptomatic individuals by salivary and nasal RT-LAMP, as well as a sensitivity of 100% and a specificity of 97.6% for the detection of SARS-CoV-2 in asymptomatic individuals. These findings indicated that performance of the direct RT-LAMP test using saliva and nasal samples has high sensitivity and specificity, which in turn suggest that it is a viable and reliable alternative for use in epidemiological monitoring.

Characteristics and outcomes of multisystem inflammatory syndrome in children: A multicenter, retrospective, observational cohort study in Mexico.

Introduction: Multisystem inflammatory syndrome in children associated with coronavirus disease 2019 (MIS-C), a novel hyperinflammatory condition secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with severe outcomes such as coronary artery aneurysm and death. Methods: This multicenter, retrospective, observational cohort study including eight centers in Mexico, aimed to describe the clinical characteristics and outcomes of patients with MIS-C. Patient data were evaluated using latent class analysis (LCA) to categorize patients into three phenotypes: toxic shock syndrome-like (TSSL)-MIS-C, Kawasaki disease-like (KDL)-MIS-C, and nonspecific MIS-C (NS-MIS-C). Risk factors for adverse outcomes were estimated using multilevel mixed-effects logistic regression. Results: The study included 239 patients with MIS-C, including 61 (26%), 70 (29%), and 108 (45%) patients in the TSSL-MIS-C, KDL-MIS-C, and NS-MIS-C groups, respectively. Fifty-four percent of the patients were admitted to the intensive care unit, and 42%, 78%, and 41% received intravenous immunoglobulin, systemic glucocorticoids, and anticoagulants, respectively. Coronary artery dilatation and aneurysms were found in 5.7% and 13.2% of the patients in whom coronary artery diameter was measured, respectively. Any cause in-hospital mortality was 5.4%. Hospitalization after ten days of symptoms was associated with coronary artery abnormalities (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.2-2.0). Age ≥10 years (OR: 5.6, 95% CI: 1.4-2.04), severe underlying condition (OR: 9.3, 95% CI: 2.8-31.0), platelet count <150,000 /mm3 (OR: 4.2, 95% CI: 1.2-14.7), international normalized ratio >1.2 (OR: 3.8, 95% CI: 1.05-13.9), and serum ferritin concentration >1,500 mg/dl at admission (OR: 52, 95% CI: 5.9-463) were risk factors for death. Discussion: Mortality in patients with MIS-C was higher than reported in other series, probably because of a high rate of cases with serious underlying diseases.

Sperm concentrations do not correlate with semen parameters and hormone profiles in males recovered from COVID-19.

Background: Although the negative impact on fertility of men recovered from coronavirus disease 2019 (COVID-19) has been suggested, there is insufficient evidence, and the data are limited and contradictory. The present prospective study aimed to evaluate the sex-related hormones, semen parameters, erectile dysfunction (ED), and lower urinary tract symptoms (LUTS) in a cohort of men who recovered from COVID-19 and age-matched control men. Methods: Semen samples were collected from twenty-two men recovered from COVID-19 with a median time of 91.5 days and thirty-six control males. The semen parameters were evaluated according to the World Health Organization (WHO) laboratory manual to examine and process human semen. The blood samples were collected to assess the male hormone profile. ED and LUTS were evaluated with the International Index of Erectile Function 5 (IIEF-5) and the International Prostate Symptom Score (IPSS), respectively. Results: The follicle-stimulating hormone (FSH) (3.819±1.515 IU/L), luteinizing hormone (LH) (4.023±1.792 IU/L), prolactin (PRL) [12.60 (10.72-15.20) ng/mL], and testosterone (T) [4.345 (3.565-5.525) ng/mL] levels were at normal range in all males enrolled in the study. Levels of semen volume (control: 2.5 mL vs. COVID-19: 1.9 mL; P<0.05) and sperm concentration (control: 59×106/mL vs. COVID-19: 41.5×106/mL; P<0.005) were significantly lower in males recovered from COVID-19, but still technically well within normal regardless of WHO edition. All variables were examined through logistic regression analysis, demonstrating that only sperm concentration was an independent variable associated with men recovered from COVID-19 [odds ratio (OR) =1; 95% confidence interval (CI): 0.999-1.098; P=0.016]. According to correlation analysis, there was no correlation between sperm concentration and other semen parameters and sex-related hormone profiles. Furthermore, an absence of ED and LUTS in men who recovered from COVID-19 was evidenced using the IIEF-5 and IPSS, respectively. Conclusions: Reproductive-age males recovered from COVID-19 have normal sperm concentration. Sperm concentration did not correlate with other semen parameters, sex-related hormones, IIEF-5, and IPSS. Further studies should be performed to evaluate whether the lower sperm concentration and semen volume that were still within the normal range are a transient or prolonged downregulation resulting from the COVID-19 attack.

SARS-CoV-2 Omicron Replacement of Delta as Predominant Variant, Puerto Rico.

We reconstructed the SARS-CoV-2 epidemic caused by Omicron variant in Puerto Rico by sampling genomes collected during October 2021-May 2022. Our study revealed that Omicron BA.1 emerged and replaced Delta as the predominant variant in December 2021. Increased transmission rates and a dynamic landscape of Omicron sublineage infections followed.

SARS-CoV-2 Spillback to Wild Coatis in Sylvatic-Urban Hotspot, Brazil.

We tested coatis (Nasua nasua) living in an urban park near a densely populated area of Brazil and found natural SARS-CoV-2 Zeta variant infections by using quantitative reverse transcription PCR, genomic sequencing, and serologic surveillance. We recommend a One Health strategy to improve surveillance of and response to COVID-19.

Use of threshold PEP with an adult non-rebreather oxygen mask plus prone positioning in acute hypoxemic respiratory failure due to SARS-CoV-2 infection during the collapse of the health system in a low-income country.

During the coronavirus disease 2019 pandemic, Ecuador reported a collapse of the healthcare system, in which intensive care unit beds were lacking. Therefore, we sought to determine whether the use of threshold expiratory positive pressure with an adult non-rebreather oxygen mask plus prone positioning is useful for improving oxygenation. Twelve patients were included. Eight patients (66.7%) survived, while four patients (33.3%) died. Baseline arterial oxygen saturation (%) prior placement median (interquartile range) 85.5% (80%-89%) and arterial oxygen saturation (%) post placement of the device was median (interquartile range) (93%-96%) (P = 0.0001). Respiratory rate before placement was median (interquartile range) 38 (36-42) and post placement of the device was median (interquartile range) 24 (22-30) (P = 0.0005). The use of an adapted device might be useful for the management of acute hypoxemic respiratory failure due to severe acute respiratory syndrome coronavirus 2 pneumonia, particularly when mechanical ventilators and high-flow oxygen systems are unavailable.

Monitoring Temporal Changes in SARS-CoV-2 Spike Antibody Levels and Variant-Specific Risk for Infection, Dominican Republic, March 2021-August 2022.

To assess changes in SARS-CoV-2 spike binding antibody prevalence in the Dominican Republic and implications for immunologic protection against variants of concern, we prospectively enrolled 2,300 patients with undifferentiated febrile illnesses in a study during March 2021-August 2022. We tested serum samples for spike antibodies and tested nasopharyngeal samples for acute SARS-CoV-2 infection using a reverse transcription PCR nucleic acid amplification test. Geometric mean spike antibody titers increased from 6.6 (95% CI 5.1-8.7) binding antibody units (BAU)/mL during March-June 2021 to 1,332 (95% CI 1,055-1,682) BAU/mL during May-August 2022. Multivariable binomial odds ratios for acute infection were 0.55 (95% CI 0.40-0.74), 0.38 (95% CI 0.27-0.55), and 0.27 (95% CI 0.18-0.40) for the second, third, and fourth versus the first anti-spike quartile; findings were similar by viral strain. Combining serologic and virologic screening might enable monitoring of discrete population immunologic markers and their implications for emergent variant transmission.

Incipient Parallel Evolution of SARS-CoV-2 Deltacron Variant in South Brazil.

With the coexistence of multiple lineages and increased international travel, recombination and gene flow are likely to become increasingly important in the adaptive evolution of SARS-CoV-2. These processes could result in genetic introgression and the incipient parallel evolution of multiple recombinant lineages. However, identifying recombinant lineages is challenging, and the true extent of recombinant evolution in SARS-CoV-2 may be underestimated. This study describes the first SARS-CoV-2 Deltacron recombinant case identified in Brazil. We demonstrate that the recombination breakpoint is at the beginning of the Spike gene. The 5' genome portion (circa 22 kb) resembles the AY.101 (Delta), and the 3' genome portion (circa 8 kb nucleotides) is most similar to the BA.1.1 (Omicron). Furthermore, evolutionary genomic analyses indicate that the new strain emerged after a single recombination event between lineages of diverse geographical locations in December 2021 in South Brazil. This Deltacron, AYBA-RS, is one of the dozens of recombinants described in 2022. The submission of only four sequences in the GISAID database suggests that this lineage had a minor epidemiological impact. However, the recent emergence of this and other Deltacron recombinant lineages (XD, XF, and XS) suggests that gene flow and recombination may play an increasingly important role in the COVID-19 pandemic. We explain the evolutionary and population genetic theory that supports this assertion, concluding that this stresses the need for continued genomic surveillance. This monitoring is vital for countries where multiple variants are present, as well as for countries that receive significant inbound international travel.

Molecular aspects of COVID-19 and its relationship with obesity and physical activity: a narrative review

Abstract BACKGROUND: Severe acute respiratory syndrome coronavirus 2 has several mechanisms of action related to inflammatory responses, especially in individuals diagnosed with obesity. This hyperinflammatory clinical profile resulting from the association between obesity and coronavirus disease 2019 (COVID-19) may be attenuated by regular physical activity. OBJECTIVE: The aim of this study was to review the evidence on the consequences of physical inactivity and physical activity on COVID-19 in patients with obesity. DESIGN AND SETTING: Narrative review at the Bahiana School of Medicine and Public Health in Salvador, Brazil. METHODS: We searched evidence on the association of COVID-19 with physical activity and obesity using the following keywords: "covid-19," "physical activity," and "obesity". The databases used were MEDLINE (PubMed), ScienceDirect, and Virtual Health Library. Studies published from 2019 to 2021 and available in Portuguese, English, and Spanish were included. The final search was conducted on September 26, 2021. RESULTS: We identified 661 studies in the database, among which 71 were considered for inclusion in the narrative review of the molecular aspects of COVID-19 and its relationship with physical activity and obesity. CONCLUSION: This literature review enabled the perception of the relationship between the molecular mechanisms of COVID-19 and obesity. Regular physical activity had various benefits for the inflammatory condition of the studied population, highlighting moderate-intensity.

Molecular evolution and structural analyses of the spike glycoprotein from Brazilian SARS-CoV-2 genomes: the impact of selected mutations.

The COVID-19 pandemic caused by SARS-CoV-2 has reached by February 2022 more than 380 million cases and 5.5 million deaths worldwide since its beginning in late 2019, leading to enhanced concern in the scientific community and the general population. One of the most important pieces of this host-pathogen interaction is the spike protein, which binds to the hACE2 cell receptor, mediates the membrane fusion and is the major target of neutralizing antibodies against SARS-CoV-2. The multiple amino acid substitutions observed in this region, specially in RBD have enhanced the hACE2 binding affinity and led to several modifications in the mechanisms of SARS-CoV-2 pathogenesis, improving the viral fitness and/or promoting immune evasion, with potential impact in the vaccine development. In this work, we identified 48 sites under selective pressures, 17 of them with the strongest evidence by the HyPhy tests, including VOC related mutation sites 138, 142, 222, 262, 484, 681, and 845, among others. The coevolutionary analysis identified 28 sites found not to be conditionally independent, such as E484K-N501Y. The molecular dynamics and free energy estimates showed the structural stabilizing effect and the higher impact of E484K for enhanced binding affinity between the spike RBD and hACE2 in P.1 and P.2 lineages (specially with L452V). Structural changes were also identified in the hACE molecule when interacting with B.1.1.7 RDB. Despite some destabilizing substitutions, a stabilizing effect was identified for the majority of the positively selected mutations.Communicated by Ramaswamy H. Sarma.

Risk for Severe Illness and Death among Pediatric Patients with Down Syndrome Hospitalized for COVID-19, Brazil.

Down syndrome is the most common human chromosomal disorder. Whether Down syndrome is a risk factor for severe COVID-19 outcomes in pediatric patients remains unclear, especially in low-to-middle income countries. We gathered data on patients <18 years of age with SARS-CoV-2 infection from a national registry in Brazil to assess the risk for severe outcomes among patients with Down syndrome. We included data from 14,684 hospitalized patients, 261 of whom had Down syndrome. After adjustments for sociodemographic and medical factors, patients with Down syndrome had 1.8 times higher odds of dying from COVID-19 (odds ratio 1.82, 95% CI 1.22-2.68) and 27% longer recovery times (hazard ratio 0.73, 95% CI 0.61-0.86) than patients without Down syndrome. We found Down syndrome was associated with increased risk for severe illness and death among COVID-19 patients. Guidelines for managing COVID-19 among pediatric patients with Down syndrome could improve outcomes for this population.

Incorporating COVID-19 into Acute Febrile Illness Surveillance Systems, Belize, Kenya, Ethiopia, Peru, and Liberia, 2020-2021.

Existing acute febrile illness (AFI) surveillance systems can be leveraged to identify and characterize emerging pathogens, such as SARS-CoV-2, which causes COVID-19. The US Centers for Disease Control and Prevention collaborated with ministries of health and implementing partners in Belize, Ethiopia, Kenya, Liberia, and Peru to adapt AFI surveillance systems to generate COVID-19 response information. Staff at sentinel sites collected epidemiologic data from persons meeting AFI criteria and specimens for SARS-CoV-2 testing. A total of 5,501 patients with AFI were enrolled during March 2020-October 2021; >69% underwent SARS-CoV-2 testing. Percentage positivity for SARS-CoV-2 ranged from 4% (87/2,151, Kenya) to 19% (22/115, Ethiopia). We show SARS-CoV-2 testing was successfully integrated into AFI surveillance in 5 low- to middle-income countries to detect COVID-19 within AFI care-seeking populations. AFI surveillance systems can be used to build capacity to detect and respond to both emerging and endemic infectious disease threats.