Continuous Glucose Monitoring for Patients with COVID-19 Pneumonia: Initial Experience at a Tertiary Care Center.

OBJECTIVE: Patients hospitalized with COVID-19 and hyperglycemia require frequent glucose monitoring, usually performed with glucometers. Continuous glucose monitors (CGMs) are common in the outpatient setting but not yet approved for hospital use. We evaluated CGM accuracy, safety for insulin dosing, and CGM clinical reliability in 20 adult patients hospitalized with COVID-19 and hyperglycemia. METHODS: Study patients were fitted with a remotely monitored CGM. CGM values were evaluated against glucometer readings. The CGM sensor calibration was performed if necessary. CGM values were used to dose insulin, without glucometer confirmation. RESULTS: CGM accuracy against glucometer, expressed as mean absolute relative difference (MARD), was calculated using 812 paired glucometer-CGM values. The aggregate MARD was 10.4%. For time in range and grades 1 and 2 hyperglycemia, MARD was 11.4%, 9.4%, and 9.1%, respectively, with a small variation between medical floors and intensive care units. There was no MARD correlation with mean arterial blood pressure levels, oxygen saturation, daily hemoglobin levels, and glomerular filtration rates. CGM clinical reliability was high, with 99.7% of the CGM values falling within the "safe" zones of Clarke error grid. After CGM placement, the frequency of glucometer measurements decreased from 5 to 3 and then 2 per day, reducing nurse presence in patient rooms and limiting viral exposure. CONCLUSION: With twice daily, on-demand calibration, the inpatient CGM use was safe for insulin dosing, decreasing the frequency of glucometer fingersticks. For glucose levels >70 mg/dL, CGMs showed adequate accuracy, without interference from vital and laboratory values.

Evaluation of procalcitonin elevation during ICU stay and its relationship with mortality in ICU patients for COVID-19 with respiratory involvement. A multicenter prospective cohort study.

Introduction: A multicenter prospective cohort study studied patients admitted to the intensive care unit (ICU) by coronavirus-19 (COVID-19) with respiratory involvement. We observed the number of occasions in which the value of procalcitonin (PCT) was higher than 0.5 ng/ml. Objective: Evaluation of PCT elevation and influence on mortality in patients admitted to the ICU for COVID-19 with respiratory involvement. Measurements and main results: We studied 201 patients. On the day of admission, acute physiology and chronic health evaluation (APACHE)-II was 13 (10-16) points. In-hospital mortality was 36.8%. During ICU stay, 104 patients presented 1 or more episodes of PCT elevation and 60 (57.7%) died and 97 patients did not present any episodes of PCT elevation and only 14 (14.4%) died (p < 0.001). Multivariable analysis showed that mortality was associated with APACHE-II: [odds ratio (OR): 1.13 (1.04-1.23)], acute kidney injury [OR: 2.21 (1.1-4.42)] and with the presentation of one or more episodes of escalating PCT: [OR: 5.07 (2.44-10.53)]. Of 71 patients who died, 59.2% had an elevated PCT value on the last day, and of the 124 patients who survived, only 3.2% had an elevated PCT value on the last day (p < 0.001). On the last day of the ICU stay, the sequential organ failure assessment (SOFA) score of those who died was 9 (6-11) and 1 (0-2) points in survivors (p < 0.001). Of the 42 patients who died and in whom PCT was elevated on the last day, 71.4% were considered to have a mainly non-respiratory cause of death. Conclusion: In patients admitted to the ICU by COVID-19 with respiratory involvement, numerous episodes of PCT elevation are observed, related to mortality. PCT was elevated on the last day in more than half of the patients who died. Serial assessment of procalcitonin in these patients is useful because it alerts to situations of high risk of death. This may be useful in the future to improve the treatment and prognosis of these patients.

Emergence and evolution of SARS-CoV-2 genetic variants during the Cuban epidemic.

The SARS CoV-2 D614G variant circulated in Cuba in 2020. New viral variants were detected after the opening of the border in November 2020. We show the results of the genomic surveillance in Cuba from December 28, 2020, to September 28, 2021 and their relationship to the epidemiological situation in the country. A total of 1,406 nasopharyngeal exudates from COVID-19 patients were processed for RNA extraction and the 1836 bp fragment of the spike gene was amplified and sequenced. The mutations present were determined using the GISAID database. Prevalence ratios were estimated by fitting Poisson univariate and multivariate regression models to investigate associations between SARS-CoV-2 variant group (VOC, non-VOC) and disease outcome. Seventeen genetic variants were detected including VOC Alpha, Beta, Gamma and Delta, one variant of interest (VOI) (Lambda) and two previous VOI (A.2.5.1 and Zeta/P.2). Beta (34.77%), Delta (24.89%) and D614G (19%) variants were the most frequently detected. By June, Delta increased in frequency, displacing Beta. Disease severity increased significantly with age and VOC (PR =1.98, IC 95%: 1.33-3.05, p <0.05). Genomic surveillance allowed us to identify the upsurge of novel variants. Coinciding with the higher epidemic period, multiple variants were co-circulating. Although we cannot rule out that failure in the transmission containment measures occurred, the increase in the number of cases associated with the circulation of several variants, particularly the Beta and Delta variants is highly suggestive. A greater association of Beta variant with clinical severity and Delta variant with a greater transmissibility was observed.

Tiny Regulators in Viral Infection: Carving SARS-CoV-2 by miRNAs.

Viruses are microscopic biological entities that can cause diseases. Viruses require a host cell to replicate and generate progeny. Once inside, viruses hijack the main cellular machinery for their benefit, disrupting cell functions and causing detrimental effects on cell physiology. MicroRNAs are short, non-coding RNAs that regulate gene expression. Recent works have shown that cell-miRNAs can modulate antiviral defense during viral infection, and viruses can disrupt these existing miRNA networks. Furthermore, multiple RNA viruses encode their own miRNAs to evade the host immune response. In this review, we analyze the activities of both, miRNAs as pro-viral modulators and miRNAs as anti-viral agents and their relationship with the development of the disease.

Suicide numbers during the first 9-15 months of the COVID-19 pandemic compared with pre-existing trends: An interrupted time series analysis in 33 countries.

Background: Predicted increases in suicide were not generally observed in the early months of the COVID-19 pandemic. However, the picture may be changing and patterns might vary across demographic groups. We aimed to provide a timely, granular picture of the pandemic's impact on suicides globally. Methods: We identified suicide data from official public-sector sources for countries/areas-within-countries, searching websites and academic literature and contacting data custodians and authors as necessary. We sent our first data request on 22nd June 2021 and stopped collecting data on 31st October 2021. We used interrupted time series (ITS) analyses to model the association between the pandemic's emergence and total suicides and suicides by sex-, age- and sex-by-age in each country/area-within-country. We compared the observed and expected numbers of suicides in the pandemic's first nine and first 10-15 months and used meta-regression to explore sources of variation. Findings: We sourced data from 33 countries (24 high-income, six upper-middle-income, three lower-middle-income; 25 with whole-country data, 12 with data for area(s)-within-the-country, four with both). There was no evidence of greater-than-expected numbers of suicides in the majority of countries/areas-within-countries in any analysis; more commonly, there was evidence of lower-than-expected numbers. Certain sex, age and sex-by-age groups stood out as potentially concerning, but these were not consistent across countries/areas-within-countries. In the meta-regression, different patterns were not explained by countries' COVID-19 mortality rate, stringency of public health response, economic support level, or presence of a national suicide prevention strategy. Nor were they explained by countries' income level, although the meta-regression only included data from high-income and upper-middle-income countries, and there were suggestions from the ITS analyses that lower-middle-income countries fared less well. Interpretation: Although there are some countries/areas-within-countries where overall suicide numbers and numbers for certain sex- and age-based groups are greater-than-expected, these countries/areas-within-countries are in the minority. Any upward movement in suicide numbers in any place or group is concerning, and we need to remain alert to and respond to changes as the pandemic and its mental health and economic consequences continue. Funding: None.

Nanobodies Protecting From Lethal SARS-CoV-2 Infection Target Receptor Binding Epitopes Preserved in Virus Variants Other Than Omicron.

The emergence of SARS-CoV-2 variants that escape from immune neutralization are challenging vaccines and antibodies developed to stop the COVID-19 pandemic. Thus, it is important to establish therapeutics directed toward multiple or specific SARS-CoV-2 variants. The envelope spike (S) glycoprotein of SARS-CoV-2 is the key target of neutralizing antibodies (Abs). We selected a panel of nine nanobodies (Nbs) from dromedary camels immunized with the receptor-binding domain (RBD) of the S, and engineered Nb fusions as humanized heavy chain Abs (hcAbs). Nbs and derived hcAbs bound with subnanomolar or picomolar affinities to the S and its RBD, and S-binding cross-competition clustered them in two different groups. Most of the hcAbs hindered RBD binding to its human ACE2 (hACE2) receptor, blocked cell entry of viruses pseudotyped with the S protein and neutralized SARS-CoV-2 infection in cell cultures. Four potent neutralizing hcAbs prevented the progression to lethal SARS-CoV-2 infection in hACE2-transgenic mice, demonstrating their therapeutic potential. Cryo-electron microscopy identified Nb binding epitopes in and out the receptor binding motif (RBM), and showed different ways to prevent virus binding to its cell entry receptor. The Nb binding modes were consistent with its recognition of SARS-CoV-2 RBD variants; mono and bispecific hcAbs efficiently bound all variants of concern except omicron, which emphasized the immune escape capacity of this latest variant.

SARS-CoV-2: theoretical analysis of the proposed algorithms to the enhancement and segmentation of high-resolution microscopy images-Part II.

Today is a reality that the novel coronavirus SARS-Cov-2 has become a global pandemic. For this reason, the study of real microscopic images of this coronavirus is of great importance, as it allows us to carry out a more precise research on it. However, as we pointed out in a former paper as reported by Roberto Rodríguez (SARS-CoV-2: Enhancement and Segmentation of High-Resolution Microscopy Images. Part I", Sent to Signal, Image and Video Processing Video Processing, Springer, New York, 2020), many times these microscopic images present some blurring problems, which are always susceptible to be improved. The aim of this work is to carry out a theoretical analysis of the proposed algorithms to enhancement and segmentation of these microscopic images, which is important for the design and development of future algorithms before new epidemics.

Asymptomatic SARS-CoV-2 Infection in Havana, Cuba, March-June 2020: Epidemiological Implications.

INTRODUCTION: The percentage of asymptomatic COVID-19 cases worldwide is estimated at 18-50%; 53% in Cuba specifically, and 58% in Havana, the Cuban capital and the 2020 epicenter of the country's COVID-19 epidemic. These figures, however, do not represent the transmission capacity or behavior of asymptomatic cases. Understanding asymptomatic transmission's contribution to SARS-CoV-2 spread is of great importance to disease control and prevention. OBJECTIVE: Identify the epidemiological implications of asymptomatic SARS-CoV-2 infection in Havana, Cuba, during the first wave of the epidemic in 2020. METHODS: We carried out a cross-sectional study of all confirmed COVID-19 cases diagnosed in Havana, Cuba, from March 16 through June 30, 2020. The information was obtained through review of the standardized form for investigation of suspected and confirmed cases. Examined variables included age, sex, occupation, case type and source of infection. Cases were divided into asymptomatic and symptomatic groups, and transmission was characterized through the creation of a contact matrix. Analysis was carried out in Epidat and R. RESULTS: We studied 1287 confirmed cases, of which 57.7% (743) were asymptomatic, and 42.3% (544) were symptomatic. Symptomatic presentation was the most common for both imported and introduced cases, while asymptomatic presentation was more common in autochthonic cases and infections from an undetermined source. Asymptomatic infection was more common in groups aged ⟨20 and 20-59 years, while symptomatic infection was more common in those aged ⟩60 years. In the contact matrix, 34.6% of cases (445/1287) were not tied to other cases, and 65.4% (842/1287) were infectious-infected dyads, with symptomatic-symptomatic being the most common combination. The majority of primary cases (78.5%; 1002/1276) did not generate secondary cases, and 85.6% (658/743) of asymptomatic cases did not lead to other cases (although one asymptomatic superspreader led to 90 cases in a single event). However, 63.2% (344/544) of symptomatic primary cases generated secondary cases, and 11 symptomatic superspreaders spawned 100 secondary cases in different events. CONCLUSIONS: Asymptomatic SARS-CoV-2 infection was the most common form of COVID-19 in Havana during the study period, but its capacity for contagion was lower than that of symptomatic individuals. Superspreader events under specific conditions played an important role in sustaining the epidemic.

Full efficacy and long-term immunogenicity induced by the SARS-CoV-2 vaccine candidate MVA-CoV2-S in mice.

Two doses of the MVA-CoV2-S vaccine candidate expressing the SARS-CoV-2 spike (S) protein protected K18-hACE2 transgenic mice from a lethal dose of SARS-CoV-2. This vaccination regimen prevented virus replication in the lungs, reduced lung pathology, and diminished levels of pro-inflammatory cytokines. High titers of IgG antibodies against S and receptor-binding domain (RBD) proteins and of neutralizing antibodies were induced against parental virus and variants of concern, markers that correlated with protection. Similar SARS-CoV-2-specific antibody responses were observed at prechallenge and postchallenge in the two-dose regimen, while the single-dose treatment does not avoid vaccine breakthrough infection. All vaccinated animals survived infection and were also protected to SARS-CoV-2 reinfection. Furthermore, two MVA-CoV2-S doses induced long-term memory S-specific humoral and cellular immune responses in C57BL/6 mice, 6 months after immunization. The efficacy and immunological benefits of the MVA-CoV2-S vaccine candidate against COVID-19 supports its consideration for human clinical trials.

SARS-CoV-2: preliminary study of infected human nasopharyngeal tissue by high resolution microscopy.

BACKGROUND: The novel coronavirus SARS-CoV-2 is the etiological agent of COVID-19. This virus has become one of the most dangerous in recent times with a very high rate of transmission. At present, several publications show the typical crown-shape of the novel coronavirus grown in cell cultures. However, an integral ultramicroscopy study done directly from clinical specimens has not been published. METHODS: Nasopharyngeal swabs were collected from 12 Cuban individuals, six asymptomatic and RT-PCR negative (negative control) and six others from a COVID-19 symptomatic and RT-PCR positive for SARS CoV-2. Samples were treated with an aldehyde solution and processed by scanning electron microscopy (SEM), confocal microscopy (CM) and, atomic force microscopy. Improvement and segmentation of coronavirus images were performed by a novel mathematical image enhancement algorithm. RESULTS: The images of the negative control sample showed the characteristic healthy microvilli morphology at the apical region of the nasal epithelial cells. As expected, they do not display virus-like structures. The images of the positive sample showed characteristic coronavirus-like particles and evident destruction of microvilli. In some regions, virions budding through the cell membrane were observed. Microvilli destruction could explain the anosmia reported by some patients. Virus-particles emerging from the cell-surface with a variable size ranging from 80 to 400 nm were observed by SEM. Viral antigen was identified in the apical cells zone by CM. CONCLUSIONS: The integral microscopy study showed that SARS-CoV-2 has a similar image to SARS-CoV. The application of several high-resolution microscopy techniques to nasopharyngeal samples awaits future use.

Estimating the impact of the COVID-19 pandemic on diagnosis and survival of five cancers in Chile from 2020 to 2030: a simulation-based analysis.

BACKGROUND: The COVID-19 pandemic has strained health system capacity worldwide due to a surge of hospital admissions, while mitigation measures have simultaneously reduced patients' access to health care, affecting the diagnosis and treatment of other diseases such as cancer. We estimated the impact of delayed diagnosis on cancer outcomes in Chile using a novel modelling approach to inform policies and planning to mitigate the forthcoming cancer-related health impacts of the pandemic in Chile. METHODS: We developed a microsimulation model of five cancers in Chile (breast, cervix, colorectal, prostate, and stomach) for which reliable data were available, which simulates cancer incidence and progression in a nationally representative virtual population, as well as stage-specific cancer detection and survival probabilities. We calibrated the model to empirical data on monthly detected cases, as well as stage at diagnosis and 5-year net survival. We accounted for the impact of COVID-19 on excess mortality and cancer detection by month during the pandemic, and projected diagnosed cancer cases and outcomes of stage at diagnosis and survival up to 2030. For comparison, we simulated a no COVID-19 scenario in which the impacts of COVID-19 on excess mortality and cancer detection were removed. FINDINGS: Our modelling showed a sharp decrease in the number of diagnosed cancer cases during the COVID-19 pandemic, with a large projected short-term increase in future diagnosed cases. Due to the projected backlog in diagnosis, we estimated that in 2021 there will be an extra 3198 cases (95% uncertainty interval [UI] 1356-5017) diagnosed among the five modelled cancers, an increase of nearly 14% compared with the no COVID-19 scenario, falling to a projected 10% increase in 2022 with 2674 extra cases (1318-4032) diagnosed. As a result of delayed diagnosis, we found a worse stage distribution for detected cancers in 2020-22, which is estimated to lead to 3542 excess cancer deaths (95% UI 2236-4816) in 2022-30, compared with the no COVID-19 scenario, among the five modelled cancers, most of which (3299 deaths, 2151-4431) are projected to occur before 2025. INTERPRETATION: In addition to a large projected surge in diagnosed cancer cases, we found that delays in diagnosis will result in worse cancer stage at presentation, leading to worse survival outcomes. These findings can help to inform surge capacity planning and highlight the importance of ensuring appropriate health system capacity levels to detect and care for the increased cancer cases in the coming years, while maintaining the timeliness and quality of cancer care. Potential delays in treatment and adverse impacts on quality of care, which were not considered in this model, are likely to contribute to even more excess deaths from cancer than projected. FUNDING: Harvard TH Chan School of Public Health. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease.

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico-informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, "Adrenergic receptor antagonist", "ATPase inhibitor", "NF-kB pathway inhibitor" and "Serotonin receptor antagonist", were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.

SARS-CoV-2: enhancement and segmentation of high-resolution microscopy images-Part I.

Possibly, and due to poor eating habits and unhealthy lifestyle, many viruses are transmitted to human people. Such is the case, of the novel coronavirus SARS-Cov-2, which has expanded of exponential way, practically, to whole world population. For this reason, the enhancement of real microscopic images of this coronavirus is of great importance. Of this way, one can highlight the S-spikes and visualizing those areas that show a high density, which are related to active zones of viral germination and major spread of the virus. The SARS-Cov-2 images were captured from nasopharyngeal samples of Cuban symptomatic individuals (RT-PCR positives for SARS-CoV-2) and processed via scanning electron microscopy. However, many times these microscopic images present some blurring problems, and the S-spikes do not look well defined. Therefore, the aim of this work is to propose new computational methods to carry out enhancement and segmentation of SARS-Cov-2 high-resolution microscopic images. The proposed strategy obtained very satisfactory results, and we validated its performance, together with specialist physicians, on a set of 1005 images. Due to the importance of the obtained results, this first work will be addressed to the application of the proposed algorithm. A second paper will deeply analyze the theory related to these algorithms.

Fever without source as the first manifestation of SARS-CoV-2 infection in infants less than 90 days old.

Fever without source (FWS) in infants is a frequent cause of consultation at the emergency department, and the emergence of SARS-CoV-2 could affect the approach to those infants. The aim of this study is to define the clinical characteristics and rates of bacterial coinfections of infants < 90 days with FWS as the first manifestation of SARS-CoV-2 infection. This is a cross-sectional study of infants under 90 days of age with FWS and positive SARS-CoV2 PCR in nasopharyngeal swab/aspirate, attended at the emergency departments of 49 Spanish hospitals (EPICO-AEP cohort) from March 1 to June 26, 2020. Three hundred and thirty-three children with COVID-19 were included in EPICO-AEP. A total of 67/336 (20%) were infants less than 90 days old, and 27/67(40%) presented with FWS. Blood cultures were performed in 24/27(89%) and were negative in all but one (4%) who presented a Streptococcus mitis bacteremia. Urine culture was performed in 26/27(97%) children and was negative in all, except in two (7%) patients. Lumbar puncture was performed in 6/27(22%) cases, with no growth of bacteria. Two children had bacterial coinfections: 1 had UTI and bacteremia, and 1 had UTI. C-reactive was protein over 20 mg/L in two children (one with bacterial coinfection), and procalcitonin was normal in all. One child was admitted to the pediatric intensive care unit because of apnea episodes. No patients died.Conclusion: FWS was frequent in infants under 90 days of age with SARS-CoV-2 infection. Standardized markers to rule out bacterial infections remain useful in this population, and the outcome is generally good. What is Known: • Fever without source (FWS) in infants is a common cause of consultation at the emergency department, and young infants have a higher risk of serious bacterial infections (SBI). • The emergence of the new coronavirus SARS-CoV-2 could affect the approach to young infants with FWS in the emergency department. management of those children is a challenge because information about bacterial coinfection and prognosis is scarce. What is New: • SARS-CoV-2 infection should be ruled out in young infants (< 90 days of age) with FWS in areas with community transmission. • Bacterial coinfection rarely coexists in those infants. • Inflammatory markers were not increased in children without bacterial coinfection. • Outcome is good in most patients.

SARS-CoV-2 in Mexico: Beyond Detection Methods, Scope and Limitations.

The new coronavirus that was first identified in December 2019 in Wuhan China, now called SARS-CoV-2, which causes the disease called COVID-19, has spread from China to the entire world in a few months. Due to its contagious potential (R0: 5.7) and because there is still no effective treatment to stop the infection, and a vaccine for prevention it is not yet available to the general population, COVID-19 is currently considered a global health problem. The need to implement sensitive methods for the identification of individuals with COVID-19 has led to the development of different molecular and immunological tests. The importance of a timely and accurate diagnosis is essential to determine the course of the pandemic. The interpretation of the results obtained by each test as well as the factors that affect these results have not been fully described. In this review, we describe and analyze the different SARS-CoV-2 detection methods that have been performed in Mexico and are available worldwide, outlining their strengths and weaknesses. Further, a broader perspective of the correct use and interpretation of the results obtained with these diagnostic tools is proposed to improve the containment strategy and identify the true impact of the pandemic.

Analytical Chemistry Teaching Adaptation in the COVID-19 Period: Experiences and Students' Opinion

An important consequence of the COVID-19 health crisis has been the suspension of face-to-face teaching activity in all teaching levels from mid-March of the academic year 2019-2020. In this sense, changes in Complutense University of Madrid toward an e-learning methodology have been made. In this work, we describe the adaptation to an online teaching model of two degree analytical chemistry courses: Pharmacy and Food Science and Technology. A mixed model has been performed for classes, using both online synchronous and asynchronous learning. The opinion of the students about this adaptation was evaluated. Although students preferred to carry out a face-to-face teaching and learning process, they found certain advantages in the online teaching modality, such as Save time and Schedule flexibility.

Association of Early Nasopharyngeal Immune Markers With COVID-19 Clinical Outcome: Predictive Value of CCL2/MCP-1.

Early recognition of severe forms of coronavirus disease 2019 (COVID-19) is essential for an opportune and effective intervention, reducing life-risking complications. An altered inflammatory immune response seems to be associated with COVID-19's pathogenesis and progression to severity. Here we demonstrate the utility of early nasopharyngeal swab samples for detection of the early expression of immune markers and the potential value of CCL2/MCP-1 in predicting disease outcome.