Durability and extent of protection of SARS-CoV-2 antibodies among patients with COVID-19 in Metro Manila, Philippines

IntroductionInformation on the magnitude and durability of humoral immunity against COVID-19 among specific populations can guide policies on vaccination, return from isolation and physical distancing measures. The study determined the durability of SARS-CoV-2 antibodies after an initial infection among Filipinos in Metro Manila, Philippines, and the extent of protection SARS-CoV-2 antibodies confer against reinfection.MethodsWe conducted a cohort study to monitor the antibody levels of patients diagnosed with COVID-19. Receptor-binding domain (RBD)-specific antibodies were measured at Days 21, 90, 180, 270 and 360. Antibody levels were reported as geometric mean titers (GMT) with geometric standard deviation (GSD). Differences in GMT were tested using Friedman test and Kruskal Wallis test, with Bonferroni multiple comparisons procedure. Adjusted hazard ratios on the development of probable reinfection were estimated using Cox proportional models.ResultsThere were 307 study participants included in the study, with 13 dropouts. Study participants received SARS-CoV-2 vaccines at varying times, with 278 participants (90.5%) fully vaccinated by the end of study. The GMT of the study cohort increased over time, from 19.7 U/mL (GSD 11) at Day 21; to 284.5 U/mL (GSD 9.6) at Day 90; 1,061 U/mL (GSD 5.3) at Day 180; 2,003 U/mL (GSD 6.7) at Day 270; and 8,403 U/mL (GSD 3.1) at Day 360. The increase was statistically significant from Day 21 to Day 90 (p<0.0001), Day 90 to Day 180 (p=0.0005), and Day 270 to Day 360 (p<0.0001). Participants with more severe initial infection demonstrated significantly higher antibody levels compared to those with milder infection at Day 21. Sixty-four patients had probable COVID-19 reinfection (incidence of 20.8%, 95% CI 16.4, 25.8%). The GMT of these 64 patients was 411.8 U/mL (GSD 6.9) prior to the occurrence of the probable reinfection. Majority (87.5%) were fully vaccinated. Antibody titers significantly affected the risk of developing reinfection, with adjusted hazard ratio of 0.994, 95% CI 0.992-0.996, p<0.001.ConclusionAntibody levels against SARS-CoV-2 increased over a one-year follow-up. Higher antibody levels were observed among those with more severe initial infection and those vaccinated. Higher antibody levels are associated with a lower risk of probable reinfection

Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program

Altres ajuts: This work was supported by the Obra Social "La Caixa" (to M. Esteller).Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease

Acute limb ischemia in an adolescent with COVID-19 and systemic scleroderma: a case report

Abstract Background Juvenile Scleroderma is a rare autoimmune disease of the connective tissue. Its concurrence with COVID-19 can lead to limb ischemia as both disease entities are pro-inflammatory and pro-thrombotic. To date, there is no case report describing the symptomatology and course of disease in patients with juvenile Scleroderma and COVID-19. Case presentation An adolescent with acute limb ischemia presented with a history of generalized hypo-and-hyperpigmented skin lesions and mild, non-productive cough. She tested positive for SARS-CoV-2 on nasopharyngeal swab RT-PCR. Further work-up revealed elevated anti-phospholipid antibodies, anti-nuclear antibody, and D-dimer; low Protein S activity; and evidence of peripheral arterial disease on imaging studies. She was started on peripheral vasodilators, Methotrexate, and anticoagulation. Close monitoring of the affected limbs and other organs involved was done. Control of limb ischemia was achieved after 4 months of regular Cyclophosphamide infusion. Continued multi-disciplinary care was ensured for this patient. Conclusion There is evolving knowledge about the interplay of COVID-19 hyperinflammatory state and rheumatologic disorders. COVID-19 is thought to exacerbate cutaneous manifestations of autoimmune disorders via antigen protein mimicry and cytokine imbalance. Moreover, COVID-19 is characterized by complex hematopathologic processes that put a patient in a hypercoagulable state. Elevated D-dimer can be seen in both COVID-19 and systemic sclerosis owing to their pro-thrombotic sequela. There is scarcity of data on the association of Protein S activity with COVID-19 and systemic sclerosis. More studies need to be carried out to ultimately arrive at a consensus on thrombosis prophylaxis for patients with Scleroderma and COVID-19

Classification with multitemporal polarimetric SAR data

Multitemporal measurements gathered by EMISAR over the Foulum (Jutland) test site and AirSAR over the Wageningen test site provide an unrivalled opportunity to examine the factors affecting classification of northern European agricultural crops using both polarimetric and multitemporal information. Data analysis, guided by physical principles, has been used to investigate those polarimetric features most adapted to separating different classes of crops (with the emphasis on C band data). This has led to a hierarchical approach in which broad classes (e.g., spring vs. winter crops) are successively subdivided into more specific classes using the most appropriate polarimetric features. This direct scheme has been linked to statistical methods in order to permit adaptivity of the decision boundaries. Its performance is compared with data-driven methods as a function of the temporal evolution of the crop state.

ANATOMICAL AND FUNCTIONAL TESTING IN DIABETIC PATIENTS WITHOUT RETINOPATHY: Results of Optical Coherence Tomography Angiography and Visual Acuity Under Varying Contrast and Luminance Conditions.

PurposeTo assess early retinal microvascular and functional changes in diabetic patients without clinical evidence of diabetic retinopathy with optical coherence tomography angiography and central visual analyzer.MethodsThis was an observational case-control study of diabetic patients without diabetic retinopathy and nondiabetic controls. Patients underwent optical coherence tomography angiography imaging and visual acuity testing using the central visual analyzer. The foveal avascular zone area and the capillary density in the superficial and deep capillary plexuses were measured manually by a masked grader.ResultsSixty eyes from 35 diabetic patients were included in the study group, and 45 eyes from 31 nondiabetic patients were included in the control group. The foveal avascular zone area was not significantly different between the diabetic group and controls (both P > 0.05). The mean capillary density in the deep capillary plexus was significantly lower in diabetic eyes compared with control eyes (P = 0.04). The mean visual acuity in all central visual analyzer modules was significantly decreased in diabetic patients compared with controls (all P < 0.05).ConclusionOptical coherence tomography angiography was able to detect retinal microvascular changes in the deep capillary plexus, and the central visual analyzer showed signs of decreased visual acuity under conditions simulating suboptimal contrast and glare in diabetic patients without diabetic retinopathy

Reinfection rates, change in antibody titers and adverse events after COVID-19 vaccination among patients previously infected with COVID-19 in Metro Manila, Philippines: a secondary analysis of a completed cohort study

Abstract Background Variation in immune response to COVID-19 vaccines is observed among different ethnicities. We aimed to describe the reinfection rates, change in antibody titers, and adverse events among Filipinos. Methods This is a secondary analysis of a cohort study of 307 participants within one year of having COVID-19 infection. We measured COVID-19 antibody levels at pre-determined timepoints (Days 21, 90, 180, 270, and 360 from initial infection). We monitored for COVID-19 symptoms and obtained details on COVID-19 vaccination. An adjudication committee classified the participants as probable, possible, or unlikely COVID-19 reinfection. We determined the probable reinfection rate, adverse events, and the geometric mean titer (GMT) ratio of pre- and post-vaccination antibody levels according to type and brand of COVID-19 vaccine. Results At the end of the follow-up period, 287 (93.5%) out of 307 study participants were fully vaccinated, 1 was partially vaccinated (0.3%), and 19 were unvaccinated (6.2%). Among the fully vaccinated participants, those given mRNA vaccines had the lowest reinfection rate (19.2 cases/100 person-years, 95% CI 9.6, 38.4), followed by viral vector vaccines (29.8 cases/100 person-years, 95% CI 16.9, 52.4). We observed the highest reinfection rate among those given inactivated virus vaccines (32.7 cases/100 person-years, 95% CI 23.6, 45.3). The reinfection rate was 8.6 cases/100 person-years (95% CI 4.1, 17.9) for unvaccinated participants and 3.6 cases/100 person-years (95% CI 0.5, 25.3) for partially vaccinated participants. We observed the largest rise in antibody titers among those given mRNA vaccines (GMT ratio 288.5), and the smallest rise among those given inactivated virus vaccines (GMT ratio 16.7). We observed the highest percentage of adverse events following immunization with viral vector vaccines (63.8%), followed by mRNA vaccines (62.7%), and the lowest for inactivated virus vaccines (34.7%). No serious adverse events were reported. Conclusion Vaccinees given the mRNA vaccines had the lowest reinfection rate and the highest rise in antibody titers. Vaccinees given inactivated virus vaccines had the highest reinfection rate, smallest rise in antibody titers, and lowest percentage of adverse events. The small sample size and imbalanced distribution of the type of vaccines received limits the external generalizability of our results. Study Registration The cohort study was registered at the Philippine Health Research Registry on December 14, 2020 (PHRR201214-003199)

Experiences from the Philippine grassroots: impact of strengthening primary care systems on health worker satisfaction and intention to stay

Abstract Background Inequities in health access and outcomes persist in low- and middle-income countries. While strengthening primary care is integral in improving patient outcomes, primary care networks remain undervalued, underfunded, and underdeveloped in many LMICs such as the Philippines. This paper underscores the value of strengthening primary care system interventions in LMICs by examining their impact on job satisfaction and intention to stay among healthcare workers in the Philippines. Methods This study was conducted in urban, rural, and remote settings in the Philippines. A total of 36 urban, 54 rural, and 117 remote healthcare workers participated in the study. Respondents comprised all family physicians, nurses, midwives, community health workers, and staff involved in the delivery of primary care services from the sites. A questionnaire examining job satisfaction (motivators) and dissatisfaction (hygiene) factors was distributed to healthcare workers before and after system interventions were introduced across sites. Interventions included the introduction of performance-based incentives, the adoption of electronic health records, and the enhancement of diagnostic and pharmaceutical capabilities over a 1-year period. A Wilcoxon signed-rank test and a McNemar’s chi-square test were then conducted to compare pre- and post-intervention experiences for each setting. Results Among the factors examined, results revealed a significant improvement in perceived compensation fairness among urban (p = 0.001) and rural (p = 0.016) providers. The rural workforce also reported a significant improvement in medicine access (p = 0.012) post-intervention. Job motivation and turnover intention were sustained in urban and rural settings between periods. Despite the interventions introduced, a decline in perceptions towards supply accessibility, job security, and most items classified as job motivators was reported among remote providers. Paralleling this decline, remote primary care providers with the intent to stay dropped from 93% at baseline to 75% at endline (p < 0.001). Conclusion The impact of strengthening primary care on health workforce satisfaction and turnover intention varied across urban, rural, and remote settings. While select interventions such as improving compensation were promising for better-supported settings, the immediate impact of these interventions was inadequate in offsetting the infrastructural and staffing gaps experienced in disadvantaged areas. Unless these problems are comprehensively addressed, satisfaction will remain low, workforce attrition will persist as a problem, and marginalized communities will be underserved